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Review

Anticancer Potential of Natural Bark Products—A Review

by
Ema Burlacu
1 and
Corneliu Tanase
2,*
1
Residency Department, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, 38 Gheorghe Marinescu Street, 540139 Târgu Mureș, Romania
2
Department of Pharmaceutical Botany, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, 38 Gheorghe Marinescu Street, 540139 Târgu Mureș, Romania
*
Author to whom correspondence should be addressed.
Plants 2021, 10(9), 1895; https://doi.org/10.3390/plants10091895
Submission received: 4 August 2021 / Revised: 2 September 2021 / Accepted: 8 September 2021 / Published: 13 September 2021
(This article belongs to the Special Issue Anticancer Compounds in Plants)
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Abstract

:
Cell biology, plant-based extracts, structural chemistry, and laboratory in vitro or in vivo experiments are the principal aspects or interfaces that can contribute to discovering new possibilities in cancer therapy and to developing improved chemotherapeutics. Forestry residues can be used for their wealthy resource in polyphenols and other phytoconstituents known for anticancer properties. This review is designed to bring together information on the in vitro or in vivo anticancer potential of woody vascular plants especially the bark extracts (BE) and biosynthesized metallic nanoparticles (BMN) using bark extracts. Type of extracts, main phytoconstituents found in extracts responsible for the anticancer activity, and targeted cancerous cell lines were followed. The literature data were collected via Clarivate Analytics, Science Direct, PubMed, and Google Academic (2011–2021). The search terms were: bark extracts, metallic nanoparticles, silver nanoparticles, gold nanoparticles, anticancer, cytotoxic activity, antiproliferative effect, and antimetastatic potential in vitro and in vivo. All of the search terms listed above were used in different combinations. The literature data highlight the efficaciousness of the BE and BMN as anticancer agents in in vitro experiments and showed the mechanism of action and their advantage of nontoxicity on normal cells. In vitro testing has shown promising results of the BE and BMN effect on different cancer cell lines. In vivo testing is lacking and more data is necessary for drug development on animal models.

Graphical Abstract

1. Introduction

Today, cancer, or malignant disease is an alarming situation because of the uncontrolled and abnormal growth of cancer cells. The most undesirable complication of cancer is metastasis and unfortunately this causes death. High mortality in cancer patients is still persistent and the statistics are not very encouraging [1]. Drug therapies are more inefficient due to resistance to chemotherapy and because it destroys the cancer cells along with normal cells [2,3,4]. The ideal anticancer agent should be able to selectively target the cancerous cells and do no harm to the normal cells [5,6].
Cancer is one of the pathological conditions in which apoptosis plays an important role, whether it is abnormal apoptosis or a defective one. That leads to unsuppressed proliferation, which results in cancerous cells that will not naturally die. For that, scientists focused their attention on anticancer strategies for targeting the uncontrollable production of malignant cells and the disorder of apoptosis [7,8]. The collaboration between cell biology, in vitro and in vivo experiments, and structural chemistry will improve and build new anticancer agents [9].
There is a real need to discover new botanical products for developing new anticancer agents. The chemical composition of plants is still poorly studied and this should be the most important source because of their potency in the pharmacological field. Because plants have been traditionally used by humans in healing processes for centuries, and many of them have success that should be an imperative calling for assiduous research in this field. It is necessary to develop new bioactive compounds to meet the need for new drug therapies. For example, Paclitaxel (Taxol) obtained from Taxus brevifolia L., and Vincristine, Vinblastine, and Vinorelbine (Vinca alkaloids) extracted from Catharanthus roseus G. Don should remind researchers of the endless source of plants as anticancer agents [10].
The current tendency in biotechnology is to recycle and use environmentally friendly products. In this context, forest waste is now widely appreciated as a rich source of natural polyphenols, with therapeutic potential [11]. Polyphenols extracted from plant bark are widely studied, mostly in vitro, and are recommended as antioxidants, antimicrobial agents, and anticarcinogens [10]. Thus, in vitro and in vivo experiments are necessary to validate their use for the production of novel anticancerous drugs with low cost and energy [5,12].
Besides classical plant bark extracts (BE), biosynthesized metallic nanoparticles (BMN) are synthesized using ecofriendly and green-chemistry ways. These BMNs present a new interest for nanomedicine, as they are being intensively studied. It was found that BMN are potent antioxidants and antimicrobial and anticancer agents [13].
Cancer chemoprevention implicates the use of pharmacological intervention to prevent, inhibit, or reverse carcinogenesis with synthetic or natural chemical products. Less than one percent of an estimated 250.000 plants has been screened pharmacologically. The use of phytochemicals present in medicinal plants as antioxidants possess no toxicity as compared to modern drugs and are efficient against different types of cancers with no side effects [14,15,16]. This study aims to bring together in vitro and in vivo results of the anticancer potential of BE and BMNs using BE.

2. Research Methodology

The literature data were collected via Clarivate Analytics, Science Direct, PubMed, and Google Academic (2011–2021). The search terms were: bark extracts, metallic nanoparticles, silver nanoparticles, gold nanoparticles, anticancer, cytotoxic activity, antiproliferative effect, and antimetastatic potential in vitro and in vivo. All of the search terms listed above were used in different combinations.
BioRender was used for drawing the figures from manuscripts (https://app.biorender.com/, accessed on 31 August 2021) [17].

3. Anticancer Potential of Bioactive Compounds from Bark Extracts (BE) in Different Type of Suppressed Cancer Cells Lines

The plant kingdom includes a multitude of secondary compounds such as polyphenols, alkaloids, flavonoids, lignans, terpenes, and taxanes. The list continues with minerals, vitamins, oils, and other biomolecules with great anticancer potential. The anticancer potential is due to potent antioxidant activity, inhibition of cancer cell-activating proteins, activating the repair DNA mechanism, or stimulating the formation of protective enzymes of biomolecules present in BE [18].
One of the important sources of bioactive compounds is forestry waste, especially bark [19,20]. Phenolic compounds as phenolic acids, flavonoids, lignans, and stilbenes, can capture free radicals and neutralize them and can prevent the aging process of cells and protect them from carcinogens [21]. There were more than 8000 phenolic compounds present in plants and their antioxidant effect has been observed in many studies [22]. The results suggested that an increased number of phenolic compounds from BE was correlated with their anticancer activity [23]. It is shown in the literature that a combination of two or three polyphenols has a synergistic and more efficacious effect in cancer treatment than using a single one as therapy [24]. One of the combinations used was EGCG (epigallocatechin-3-gallate) and quercetin [25,26] or ECGC and resveratrol against prostate cancer cells [27]. When using similar or complementary bio compounds the anticancer effect is enhanced; the anticancer effect is managed on multiple mechanisms of action [24]. Elansary et al. [28] studied expressly the polyphenolic characterization of Malus baccata and Malus toringoides. The three main polyphenols found in BE were protocatechuic acid, gallic acid, and catechin. They exerted potent anticancer activity against breast cancer, cervical cancer, and Jurkat T cell leukemia cancer cell lines, also having antioxidant and antimicrobial capability. The same authors found in another study that Quercus species showed an increased profile of polyphenol acids such as ellagic acid, gallic acid, protocatechuic acid, vanillic acid, and caffeic acid. These bio compounds showed necrosis and apoptotic effect in cancerous cells after treatment in a dose-dependent manner [29].
The alkaloids showed a beneficial effect on normal cells and cytotoxic activity against cancerous cells. This chemical family is one of the most important biologically active secondary metabolites found in the plant kingdom with multilateral biological activities [30,31]. Gabunamine, gabunine, and tabernamine from Tabernaemontana johnstonii BE exhibited important cytotoxicity against the P-388 mouse lymphocytic leukemia cell culture system [32]. Paclitaxel obtained from BE a few decades ago is part of this family of active anticancer bio compounds and was used in the treatment of ovarian cancer. Over time this isolate compound was approved to be used in other types of cancer [33].
Terpenes are another class of bio compounds in the alkaloid family with anticancer properties. Monoterpenes can act synergistically with polyphenols or alone with great potential in anticancer activity [34]. Over 20.000 terpenes were isolated and tested as anticarcinogens and the most important are lupeol, betulin, betulinic acid, oleanoic acid, etc. [35]. It was found that monoterpenes and sesquiterpenes found in Khaya senegalensis BE exhibited anticancer activity against colorectal and cervical cancer cell lines. Another study reported that terpenes have been introduced already in clinical testing for the treatment of solid tumors [36]. The BE biocompounds summarized in this review showed their potent activity as anticarcinogens. Some phytochemicals already are used in clinical therapy while others are used in clinical trials and some are barely discovered as potent anticarcinogens [37]. The BEs are found to be a valuable source of biologically active compounds with anticancer potential (Table 1).
Being the most pronounced cancer among women, breast cancer is one of the most studied cancer types. MCF-7 and MDA-MB-231 human breast cancer cell lines are often used in experiments. Table 1 shows the variety of BE with potential against breast cancer cell lines. For example, Ydav et al. [56] showed that Saraca indica L. (Fabaceae) alcoholic BE inhibited the proliferation of breast cancer cell lines. Its activity was more prominent in MCF-7 than in MDA-MB-231 cells.
Human lung carcinoma cell migration was inhibited in a dose-dependent manner by an ultrasound-assisted extract from Fagus sylvatica L. (Fagaceae) and Picea abies L. (Pinaceae) bark. In this study, the cytotoxic effect was not observed in the A549 lung carcinoma cell line but a slight modification was observed by increasing the concentration of the samples. In another study methanolic BE of Costus pictus D.Don (Costaceae) remarkably decreased cell viability in A549 lung carcinoma cell line in a dose-dependent manner [46].
PANC-1 was one of the pancreatic cancer cell lines inhibited by the β-caryophyllene compound. This was obtained by Dahham et al. [41] from essential oil from stem BE of Aquilaria crassna. The effect was similar to one of 5-fluorouracil, betulinic acid, and tamoxifen. Dahham et al. [41] showed that β-caryophyllene from the Aquilaria crassna bark had an antiproliferative effect mostly against HCT 116 and HT29 colon cancer cell lines. Because of the effect against colon cancer cell lines, they tested the efficacy of β-caryophyllene on the HCT 116 cell line. The recorded result was that β-caryophyllene can cease colonization with its cytotoxic effect.

4. Biosynthesized Metallic Nanoparticles (BMN) Mediated by Bark Extracts as Anticancer Agents

BEs are increasingly used in metallic nanoparticle biosynthesis as bioactive compounds that have the ability to reduce metallic ions. Because these biomolecules are ecofriendly and safe for human therapeutic use, the low cost makes it suitable for large-scale production over other bioactive products [13,62,63]. BMNs are used for their potential applications as antimicrobial, antioxidant, and anticancer agents [64].
More than 65% of nanoparticles used in general biological applications are silver NPs as earlier studies have shown. That is because they have the smallest dimension and have easy access to permeate the cellular membrane and affect cellular physiology. When the diameter of a nanoparticle decreases the touching surface increases, and that has an explicit influence on their cell entrance and efficacy [63]. Beyond their nanosize, the BMN has another advantage. The biomolecules present in BE are potent stabilizing agents that are attached to the surface of the nanoparticles and also have a cytotoxic effect. That effect is combined with the size advantage and the cytotoxic effect is highlighted [65].
Silver nanoparticles have an important role in therapy for wound healing, not only in skin but also in breast cancer. In this review, the majority of cited studies are on silver NPs and the principally tested cells are breast cancer cell lines. For example, the BE AgNPs from Elaeodendron croceum displayed an IC50 value of 138.8 µg/mL against the MDA-MB-231 breast cancer cell line, comparable with the IC50 value of 80 µg/dL obtained after treatment with Paclitaxel [66].
Another study showed that approximately 82.5% of A549 lung cancer cells were dead after treatment with Toxicodendron vernicifluum (Stokes) F.A. Barkley (Anacardiaceae) AgNPs [67]. Table 2 summarizes the potential anticancer activity of BMN, specifying the type of suppressed cancer cells.

5. BE and BMNs Mechanism of AntiCancer Action

It has been reported that plant-derived extracts show a selective decrease in the growth activity of cancer cells compared to normal cells [38]. This selective targeting is due to phytochemicals present in plants as flavonoids, phenolic acids, terpenes, tannins, and steroids (Figure 1). These compounds are described as key antioxidant agents. The reasons for selective annihilation of cancerous cells and nontoxicity on normal ones remain yet unknown [46,80]. The inducing antioxidant activity of natural extracts mainly described for redox activity acts as a reducing agent, hydrogen donor, or oxygen scavenger. That might be helpful in preventing or slowing down the evolution of oxidative stress-related disorders as cancer [46,59].
Cell death appears by two alternate modes apoptosis or necrosis. These two ways are different because the first one is programmed managed cell death without a local inflammatory response. Necrosis is characterized as a passive unexpected form of cell death dependent on environmental disturbance with the unrestrained release of inflammatory response. Apoptotic cells go through diverse morphological transformations such as membrane blebbing, chromatin condensation, nuclear membrane disruption, nuclear fragmentation, and dissolution (Figure 1). The first sign of apoptosis is the apoptotic body [81]. Cell apoptosis develops through the mitochondria-mediated intrinsic pathway or death receptor-induced extrinsic pathway. It was observed that BE from Pinus massoniana has a role in both pathways. After the treatment of HeLa cells the expression of Bax, a proapoptotic protein vigorously increased. Cell apoptosis was induced by releasing of cytochrome C [82,83].
The molecular mechanism of BE from Spondias pinnata mediated apoptosis induction was observed in A549 lung carcinoma and MCF-7 breast cancer cell lines. The western blot results showed an increased expression of Bax (proapoptotic) protein and a decreased one for Bcl-2 (antiapoptotic) protein in A549 cells. The same expression was observed after treatment in MCF-7 cells. The only difference was in Bcl-2 expression that was not changed [58]. Alvala et al. [60] found that the BE of Tecomella undulata caused apoptosis on the K562 chronic myeloid leukemia cell line. That was evident after DNA fragmentation assay, increase in FAS (cell surface death receptor), FADD (FAS associated death domain protein) levels, and activation of caspase 8 and 3/7 (a cysteine protease that initiates apoptotic signaling via the extrinsic apoptotic pathway).
Alstoria scholaris and Alstoria venenata BE showed important membrane blebbing, nuclear condensation, and damage, which are manifestations of apoptosis rather than necrosis. The cytotoxic effect of BE on DLA (Dalton`s ascitic lymphoma) cells and their cytoprotective effect on normal ones may be due to their potent antioxidant activity [39].
Nayak et al. [65] studied the mechanism of silver nanoparticles obtained from the bark extracts of Azadirachta indica on the MG-63 osteosarcoma cell line after 24 h of treatment. They observed the formation of granulations in the nucleus, which is a measure of chromatin condensation. That reaction is well documented in nanoparticle treated samples before. The cytotoxic activity of metallic nanoparticles is due to their small size and affinity for the acidic pH of the cancer cells [84]. It is known that a characteristic of apoptosis is the loss of mitochondria membrane integrity and potential (Figure 2). The fluorescence signal decreases when the mitochondria lose their membrane potential and the absorption of rhodamine 123 by the affected cells is low. β-caryophyllene from Aquilaria crassna essential oil BE had a potent capacity in apoptosis-inducing. The fluorescence signal decreased in treated cancer cells PANC-1 pancreatic cancer, HCT-116, and HT29 colorectal cancer. The untreated cells showed a substantial fluorescence intensity. These results present the unaffected state of normal cells [40]. In the same way, another study revealed that β-caryophyllene oxide produces apoptosis. They found that apoptosis is produced through suppression of PI3K/AKT/mTOR/S6K1 pathways and also following ROS-mediated MAPKs activation. The first signaling pathway is not only conducting toward apoptosis but is closely related to angiogenesis and the second pathway ROS-mediated mitogen-activated protein kinases activation regulates diverse cellular actions as proliferation, motility, and survival [85].
In another study [86], the effect of BE from Acanthopanax sessiliflorus on MDA-MB-231 and MCF-7 breast cancer cell lines was shown. The intracellular ROS (reactive oxygen species) levels were determined by inspecting the fluorescent intensity of a redox reagent. It was observed that the BE elevated the proportion of green fluorescence in both cell lines dose-dependently. That suggests that the studied BE stimulates the production of intracellular ROS after the selective interruption of the mitochondrial respiratory chain. This is evidence of apoptosis with the involvement of mitochondrial membrane depolarization. In general, ROS contributed to cell death inducing the cell membrane lipid oxidation and the expression of genes associated with DNA disruption, which promotes DNA damage in apoptosis or necrosis at levels above the cellular antioxidant defense systems [8,86].
Another way for cancer cell extinction is interrupting the cell cycle. After the analysis of cellular cycles, BE from Euphorbia umbellata, showed that chloroform fraction promotes cell cycle arrest at G0/G1 phase. Moreover, treatment with this potent extract showed a decreased percentage of cells in S-phase [48]. Another study conducted by Gonzalez-Sarrias et al. [38] revealed that proliferation of colon cancer cells can be inhibited by the compounds present in the maple BE, by arresting the advancement of the cell cycle at the S-phase. In addition, cancer cells own an extra survival mechanism such as colonization, migration, tumor angiogenesis, cell adhesion, epithelial-mesenchymal transition, and transendothelial migration known as a metastatic cascade. The suppression of colonization and migration of HCT 116 colon cancer cells was demonstrated by β-caryophyllene. It also had the ability to prevent metastatic propagation of malignant cells and to suspend cell invasion, the main characteristic of metastatic cascade [41,87,88].
Toxicity on different normal cells was realized to observe the behavior of the BE. For example, cytotoxicity of the Toxicodendron vernicifluum BE was studied. The results indicated that NIH3T3 mouse embryonic fibroblasts growth was not significantly reduced and cell death was not observed at different concentrations of the extract [67].
The β-caryophyllene found in essential oil from Aquilaria crassna bark exhibited low toxicity against 3T3-L1 and RGC-5 normal cell lines. The results showed that even the higher concentration of β-caryophyllene did not affect the morphology of a normal cell line (3T3-L1) [41]. In the case of the HaCaT human keratinocytes normal cell line, the BE from Fagus sylvatica and Picea abies did not show cytotoxic activity. Instead, BE stimulated normal cells’ proliferation [49].
The in vivo toxicity of AgNPs bark extract of Elaedendron croceum was assessed on male Wister rats. The authors revealed that there was no mortality or any toxic reaction after the acute oral test. There was no toxicity observed in the heart, liver, and kidney after the morphological investigation [66]. Another efficacy advantage is that during chemical reactions in the synthesis of nanoparticles, some harmful reactants from BE are involved in capping and reducing the AgNPs. Therefore, the cytotoxic effect of AgNPs on normal cells is reduced [66]. In addition, it was observed in the literature that NPs with extremely small diameters appear to have a higher cytotoxic effect in normal cells due to swift internalization than NPs with higher diameter [89].
Accordingly, with data shown in studies, the tests effectuated on normal cells with BE and BEM exhibited no harmful or toxic effects.

6. Conclusions and Future Perspectives

Cancer has become a front line between resistance to chemotherapy, aggressive invasion, secondary toxic effects, and scientists who struggle to find a better chemical bioactive extract to maintain homeostasis, to avoid the unwanted secondary toxic effects, and to prevent metastatic cascade. BEs and BMNs are a future promise source of antioxidant compounds, which can fight against cancerous cells. All standardized extracts, shown in the listed studies above, had an impressive antioxidant capacity that was linked with anticancer ability. For maximal certainty, researchers tested in vitro the BEs and BMNs cytotoxic effect on cancer cells and normal cells. Unfortunately, in vivo studies for the anticancer potential of BEs are few. The results are encouraging and in vivo experiments should be supported. BMNs showed also antioxidant potency with great in vitro cytotoxic effect on cancer cells but no in vivo experiment was found. The toxicity on normal cells was shown as harmless. This is a promising result for the application of BEs and BMNs on animal subjects and bypasses the secondary undesirable effect of chemotherapy. There remains a need for in vivo studies to confirm the anticancer action of BEs and BMNs.

Author Contributions

Conceptualization, C.T.; methodology, C.T.; writing—original draft preparation, E.B.; writing—review and editing, C.T.; supervision, C.T.; project administration, C.T.; All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by a grant from the Romanian Ministry of Education and Research, CNS-UEFISCDI, project number PN-III-P1-1.1-TE-2019-1549, within PNCDI III.

Acknowledgments

This work was supported by a grant from the Romanian Ministry of Education and Research, CNS-UEFISCDI, project number PN-III-P1-1.1-TE-2019-1549, within PNCDI III.

Conflicts of Interest

The authors declare no conflict of interest.

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Plants 10 01895 g001 550
Figure 1. Schematic representation of cancer cell apoptosis after treatment with BE.
Figure 1. Schematic representation of cancer cell apoptosis after treatment with BE.
Plants 10 01895 g001
Plants 10 01895 g002 550
Figure 2. Schematic representation of BMN action against a cancer cell.
Figure 2. Schematic representation of BMN action against a cancer cell.
Plants 10 01895 g002
Table
Table 1. Type of cancer cells lines suppressed by bioactive compounds from BE.
Table 1. Type of cancer cells lines suppressed by bioactive compounds from BE.
Source of Bark: Scientific Name (Family)—Common NameExtracts TypeMain Bioactive CompoundsExperiment TypeType of Suppressed Cancer Cells LinesReferences
Acanthopanax sessiliflorus (Decne & Planch) Miq. (Araliaceae)—thorny ginsengn-hexane fraction of stem bark methanolic extract-In vitroMDA-MB-231 and MCF-7 human breast cancer[8]
Acer rubrum L. (Sapindaceae)—red mapleMethanolic extractPolyphenols—ginnalin-AIn vitroHCT-116 Caco-2 HT-29 colon cancer cell lines[38]
Acer saccharum March. (Sapindaceae)—sugar mapleMethanolic extractPolyphenols—ginnalin-AIn vitroHCT-116 Caco-2 HT-29 colon cancer cell lines[38]
Alstonia scholaris (L.) R.Br. (Apocynaceae)—devil`s treeHexane extract In vitroDLA: dalton`s lymphoma ascitic cell line[39]
Alstonia venenata R. Br. (Apocynaceae)Hexane extract In vitroDLA: dalton`s lymphoma ascitic cell line[39]
Antocephalus cadamba (Roxb.) Miq. (Rubiaceae)—kadamPetroleum ether
Methanolic extract		-In vivo on Swiss albino miceEAC: Ehrlich ascites carcinoma[40]
Aquilaria crassna Pierre (Thymelaeaceae)—Agar woodessential oil from stem bark extractβ-caryophylleneIn vitroPANC-1 pancreatic cancer, HCT-116 and HT29 colorectal cancer[41]
Balanite aegyptiaca (L.) Delile (Balamitaceae)—desert dateCholoform
Methanolic water
Hexane extract		AlkaloidsIn vivo antitumor activity in nude mice induced with HCT-116 tumorHCT-116 colon cancer
K562 myelogenous leukemia
U937 histyocitic lymphoma
MCF-7 breast cancer		[42]
Betula pendula Roth (Betulaceae)—common silver birch2-propanol and ethanolic extractBetulin and betulinic acidIn vitroHeLa human cervical cancer; A431 human squamous carcinoma; A2780 ovarian carcinoma; MCF-7 breast cancer[37]
Betula utilis D.Don (Betulaceae)—Himalayan silver birchEthyl acetate extractTriterpenesIn vitroMCF-7[6]
Canarium odontophyllum Miq. (Burseraceae)—dabaiAcetone extractFlavonoids
Saponins
Tannins
Terpenoids and phenolic compounds		In vitroHCT 116 colorectal cancer[43]
Catalpa speciosa Warder (Bignoniaceae)—northern catalpaMethanolic bark extractPhenolic acids catechinsIn vitroHeLa cervical cancer; MCF-7 breast cancer; Jurkat leukemic T cells; T24 urinary bladder carcinoma; HT-29 colorectal adenocarcinoma[44]
Cinnamomum zeylanicum Blume. (Lauraceae)—true cinnamon treeMethanolic extract-In vitroHepG2 hepato carcinoma[45]
Costus pictus D.Don (Costaceae)—painted spiral gingerMethanolic extract
Polyphenols FlavonoidsIn vitroHT-29 colon cancer;
A549 lung carcinoma		[46]
Crysophillum perpulchrum L. (Sapotaceae)Methanolic bark extractPolyphenolsIn vitroHeLa cervical cancer[47]
Euphorbia umbellata (Pax) Bruyns (Euphorbiaceae)—African milk bushWater and methanolic extractTriterpenes
Steroids		In vitroJurkat cells T-cell leukemia[48]
Fagus sylvatica L. (Fagaceae)—beechWater bath extraction and ultrasound-assisted extractionPolyphenolsIn vitroA375 melanoma; A549 lung carcinoma[49]
Ficus drupacea Thunb. (Moraceae) —brown-woolly figMethanolic extract, n-hexane fractionOleanolic acid,
friedelin, and
epilupeol acetate		In vitroHeLa cervical cancer; MCF-7 breast cancer; Jurkat leukemic T cells; HT-29 colorectal cancer; and T24 urinary bladder carcinoma[50]
Khaya senegalensis (Desr.) A Juss (Meliaceae)—African mahoganyMethanolic, water, and SFE (subcritical fluid extraction)Monoterpenes
Sesquiterpene		In vitroCaco 2 colorectal cancer; HeLa cervical cancer[51]
Magnolia acuminata L. (Magnoliaceae)—cucumber tree-Phenolic acids—protocatechuic acid
Catechin
Epicatechin		In vitroHeLa cervical cancer; MCF-7 breast cancer; Jurkat leukemic T cells; T24 urinary bladder carcinoma; HT-29 colorectal adenocarcinoma[44]
Malus baccata var.gracilis (Rehder) T.C.Ku. (Rosaceae)—Siberian crab appleMethanolic extractPolyphenols protocatechuic acid, gallic acid, and catechinIn vitroMCF-7 breast cancer cells, HeLa cervical cancer
Jurkat cells T cell leukemia		[28]
Malus toringoides Hughes (Rosaceae)—cut-leaf crabappleMethanolic extractPolyphenols protocatechuic acid, gallic acid, and catechinIn vitroMCF-7 breast cancer cells, HeLa cervical cancer
Jurkat cells T cell leukemia		[28]
Mangifera zeylanica (Blume) Hook. f (Anacardiaceae)—
Sri Lanka wild mango		Hexane, chloroform, ethyl acetate and methanol extractSteroids, flavonoids, phenolic compounds, and tanninsIn vitroMCF-7 and MDA-MB-231 breast cancer
SKOV-3 ovarian cancer		[1]
Moringa oleifera Lam. (Moringaceae)—drumstick treeHexane and benzene extract-In vitroDLA: dalton`s lymphoma ascitic cell line[39]
Moringa oleifera Lam. (Moringaceae)—drumstick treeEthanolic extractEugenol, isopropyl isothiocynate, D-allose, and hexadeconoic acid ethyl esterIn vitroMDA-MB-231 breast cancer
HCT–8 ileocecal adenocarcinoma		[52]
Margaritaria discoidea (Baill.) G. L. Webster (Euphorbiaceae)—pheasant-berryDichloroethane and methanol extractGallic acid
Securinine		In vitroOVCAR-8; A2780 ovarian cancer cell lines
A2780cis cisplatin resistant ovarian cancer		[53]
Oroxylum indicum (L.)Benth. Ex Kurtz (Bignoniaceae)—Indian trumpet flowerPetroleum ether
Dichloromethane
Methanol extract		Polyphenols
Flavonoids		In vitroHeLa cervical adenocarcinoma[54]
Picea abies L. (Pinaceae)—spruceWater bath extraction and ultrasound-assisted extractionPolyphenols, tannins, flavonoids, and flavonolsIn vitroA375 human melanoma; A549 lung carcinoma[49]
Pinus massoniana Lamb. (Pinaceae)—chinese red pine Flavonoids (Tannins)—proanthocyanidinsIn vitroHeLa cells cervical cancer[55]
Quercus acutissima Carruth. (Fagaceae)—Sawtooth oakMethanolic extractPhenolic acid—scaffeic acid, ellagic acid, gallic acid, and protocatechuic acidIn vitroMCF-7 breast cancer;
HeLa Cervical cancer
Jurkat T-cell leukemia cell line
[29]
Quercus macrocarpa Michx. (Fagaceae)—bur oakMethanolic extractPhenolic acids—caffeic acid and catechinsIn vitroMCF-7 breast cancer;
HeLa Cervical cancer
Jurkat T-cell leukemia cell line
[29]
Quercus robur L. (Fagaceae)—common oakMethanolic extractPhenolic acids—ellagic acid, gallic acid, protocatechuic acid, and vanillic acidIn vitroMCF-7 breast cancer;
HeLa Cervical cancer
Jurkat T-cell leukemia cell line
T24 bladder transitional cell carcinoma		[29]
Saraca indica L. (Fabaceae)—asoka-treeAlcoholic extractPolyphenolsIn vitroMCF-7, MDA-MB-231 breast cancer[56]
Sesbania grandiflora (L.) Poiret (Fabaceae)—vegetable hummingbirdEthyl alcoholic extractPhenolics terpenoids and phenolics flavonoidsIn vitroMCF-7 human breast cancer and HL-60 human leukemia[57]
Spondias pinnata L.f.Kurz (Anacardiaceae)—wild mangoWater methanolic extract-In vitroA549 lung carcinoma;
MCF-7 breast carcinoma		[58]
Stryphnodendron adstringens (Mart.) Coville (Fabaceae)—barbatimaoWater extractProanthocyanidins (Tannins)
Triterpenoids
Gallic acid
Gallocatechin
epigallocathechin		In vitroB16F10Nex-2 melanoma cells[59]
Taxus cuspidata Siebold &Zucc (Taxaceae)—Japanese yew Phenolic acidsIn vitroHeLa cervical cancer; MCF-7 breast cancer; Jurkat leukemic T cells; T24 urinary bladder carcinoma; HT-29 colorectal adenocarcinoma[44]
Tecomella undulata (Sm.) Seem. (Bignoniaceae)—desert teakChloroform extractSteroids and Triterpenes
Flavonoids		In vitroK562 erythroleukemic cell line[60]
Theobroma cacao L. (Malvaceae)—cocoa treeMethanolic extractFlavonoids
Saponins
Triterpenes
Condensed tannins
Steroids		In vitroMCF-7 breast cancer[61]
Wrghtia tinctoria (Roxb.)R. Br. (Apocynaceae)—pala indigo treeEthyl alcoholic extractAlkaloids terpenoids
Phenolics		In vitroMCF-7 human breast cancer[57]
Table
Table 2. Type of cancer cell lines suppressed by biosynthesized metalic nanoparticles (BMN) mediated by bark extracts.
Table 2. Type of cancer cell lines suppressed by biosynthesized metalic nanoparticles (BMN) mediated by bark extracts.
Source of Bark: Scientific Name (Family)—Common NameBMNs TypeExperiment TypeType of Suppressed Cancer Cell LinesReferences
Albizia chevaalieri Harms (Fabaceae) AgIn vitroMDA-MB231, MCF-7 breast cancer and HepG2 liver cancer[68]
Albizia lebbeck L. Benth. (Fabaceae)—lebbeck treeZnOIn vitroMDA-MB-231;
MCF-7 breast cancer		[69]
Azadirachta indica A.Juss. (Meliaceae)—Nimtree or Indian lillacAgIn vitroMG-63 osteosarcoma[65]
Elaeodendrum croceum (Thunb.) DC. (Celastraceae) —saffron AgIn vitroMDA-MB-231 breast cancer [66]
Ficus benghalensis L. (Moraceae)—banyan figAgIn vitroMG-63 osteosarcoma[65]
Ficus benghalensis var. krishnae L. (Moraceae)—Krishna`s butter cupAgIn vitroSKOV-3 ovarian cancer[70]
Garcinia mangostana L. (Clusiaceae)—MangosteenAgIn vitroA549 lung cancer[71]
Moringa oleifera L. (Moringaceae)—drumstick treeAgIn vitroHeLa cervical cancer[72]
Nerium oleander L. (Apocynaceae)—KarabiAuIn vitroMCF-7 breast cancer[73]
Prosopis juliflora Sw. DC. (Fabaceae)—MesquiteAgIn vitroA549 lung cancer[74]
Stereospermum suaveolens Roxb. DC.—(Bignoniaceae) Ag
Au		In vitroA549 lung cancer[75]
Syzygium alternifolium (Wt.) Walp (Myrtiaceae)—North ArcotCuIn vitroMDA-MB-231 breast cancer[76]
Terminalia arjuna Wigh and Arn
(Combretaceae)—Arjuna tree		Cu–AgIn vitroMDA-MB-231 breast cancer; HeLA cervical cancer; SiHa squamous cell carcinoma; HepG2 liver carcinoma[77]
Terminalia mantaly H. Perrier (Combretaceae)—Madagascar almond, umbrella treeAuIn vitroCaco-2 colon cancer; MCF-7 breast cancer; HepG2 liver cancer [78]
Toxicodendron vernicifluum (Stokes) F.A. Barkley (Anacardiaceae)—Chinese lacquer treeAgIn vitroA549 Adenocarcinomic human alveolar basal epithelial cells [67]
Salacia chinensis L. (Celastraceae)—Chinese salaciaAgIn vitro HepG2 liver cancer; L-132 lung cancer; MIA-Pa-Ca-2 pancreas cancer; MDA-MB-231 breast cancer; KB cells oral cancer; PC-3 prostate cancer; HeLa cervical cancer cells[79]
Ag: silver nanoparticles; Au: gold nanoparticles; Cu: copper nanoparticles; Cu–Ag: copper and silver bimetallic nanoparticles; ZnO: zinc oxide nanoparticles.
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Burlacu, E.; Tanase, C. Anticancer Potential of Natural Bark Products—A Review. Plants 2021, 10, 1895. https://doi.org/10.3390/plants10091895

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Burlacu E, Tanase C. Anticancer Potential of Natural Bark Products—A Review. Plants. 2021; 10(9):1895. https://doi.org/10.3390/plants10091895

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Burlacu, Ema, and Corneliu Tanase. 2021. "Anticancer Potential of Natural Bark Products—A Review" Plants 10, no. 9: 1895. https://doi.org/10.3390/plants10091895

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