Research

16 pages, 2489 KiB

Open AccessArticle

Antioxidant and Anti-Proliferative Properties of Hagenia abyssinica Roots and Their Potentially Active Components

by Minxia Fan, Guilin Chen, Yongli Zhang, Lutfun Nahar, Satyajit Dey Sarker, Guangwan Hu and Mingquan Guo

Antioxidants 2020, 9(2), 143; https://doi.org/10.3390/antiox9020143 - 06 Feb 2020

Cited by 20 | Viewed by 3991

Abstract

Hagenia abyssinica (Bruce) J. F. Gmel. is a multipurpose dioecious tree that has been used to treat various ailments, for example, the flowers of H. abyssinica have been widely used as a tea to treat intestinal parasites by local residents and the roots [...] Read more.

Hagenia abyssinica (Bruce) J. F. Gmel. is a multipurpose dioecious tree that has been used to treat various ailments, for example, the flowers of H. abyssinica have been widely used as a tea to treat intestinal parasites by local residents and the roots of H. abyssinica could also be used for anticancer purposes. Antioxidant activity could be one of the most important pathways to suppress cancer and there is hardly any information available on the specific chemical components corresponding to the bioactivities of H. abyssinica to date. The present study intended to screen and evaluate the antioxidant and anti-proliferative properties of five different fractions from H. abyssinica along with their corresponding total flavonoid and phenolic contents and then further identify those compounds with the most potent antioxidant and anti-proliferative activities using high performance liquid chromatography (HPLC) coupled to mass spectrometry (MS) and nuclear magnetic resonance (NMR). The total flavonoid and phenolic content assays showed that the ethyl acetate (EA) fraction of H. abyssinica had higher flavonoid and phenolic levels than the other four fractions. Furthermore, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) superoxide radical scavenging abilities, total antioxidant capacity (TAC) assay with 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS), and ferric-reducing antioxidant power (FRAP) were measured to evaluate the antioxidant activities of the five fractions and some pure compounds isolated from the EA fraction, which displayed higher antioxidant properties than that of the other fractions. Caffeic acid from the EA fraction showed even stronger DPPH scavenging ability (IC₅₀ 7.858 ± 0.31 µg/mL) than that of Vc (IC₅₀ 8.27 ± 0.11 µg/mL) as the positive control. The anti-proliferative properties of four fractions and the ethanol extract were evaluated by the 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay and the EA fraction exhibited higher anti-proliferative activities against three cancer cell lines than that of the other fractions. Additionally, the compounds with good antioxidant activity from the EA fraction of H. abyssinica were screened and identified using LC-MS and NMR and were also found to possess good anti-proliferative activity. In the MTT assay, the quercetin showed the strongest dose-dependent anti-proliferative activities to colon cancer cells (HT-29) and liver cancer cells (HepG2) among all of the compounds isolated. This study provided valuable information on the synergistic antioxidant and anti-proliferative properties of H. abyssinica. Full article

(This article belongs to the Special Issue Dietary Antioxidants in Cancer Chemoprevention)

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21 pages, 3786 KiB

Open AccessArticle

The Anti-Proliferative and Anti-Invasive Effect of Leaf Extracts of Blueberry Plants Treated with Methyl Jasmonate on Human Gastric Cancer In Vitro Is Related to Their Antioxidant Properties

by Alejandra Ribera-Fonseca, Danae Jiménez, Pamela Leal, Ismael Riquelme, Juan Carlos Roa, Miren Alberdi, Richard M. Peek and Marjorie Reyes-Díaz

Antioxidants 2020, 9(1), 45; https://doi.org/10.3390/antiox9010045 - 04 Jan 2020

Cited by 28 | Viewed by 5568

Abstract

Gastric cancer is the third main cause of cancerous tumors in humans in Chile. It is well-accepted that a diet rich in antioxidant plants could help in fighting cancer. Blueberry is a fruit crop with a high content of antioxidants. Methyl jasmonate (MeJA) [...] Read more.

Gastric cancer is the third main cause of cancerous tumors in humans in Chile. It is well-accepted that a diet rich in antioxidant plants could help in fighting cancer. Blueberry is a fruit crop with a high content of antioxidants. Methyl jasmonate (MeJA) is a phytohormone involved in plant defenses under stress conditions. The exogenous application of MeJA can improve the antioxidant properties in plants. We studied in vitro and in vivo anticancer action on human gastric cancer (cell line AGS) and the antioxidant properties of extracts from blueberry plants untreated and treated with MeJA. The results demonstrated that leaf extracts displayed a higher inhibition of cancer cell viability as well as greater antioxidant properties compared to fruit extracts. Besides, MeJA applications to plants improved the antioxidant properties of leaf extracts (mainly anthocyanins), increasing their inhibition levels on cell viability and migration. It is noteworthy that leaf extract from MeJA-treated plants significantly decreased cancer cell migration and expression of gastric cancer-related proteins, mainly related to the mitogen-activating protein kinase (MAPK) pathway. Interestingly, in all cases the anticancer and antioxidant properties of leaf extracts were strongly related. Despite highlighted outcomes, in vivo results did not indicate significant differences in Helicobacter pylori colonization nor inflammation levels in Mongolian gerbils unfed and fed with blueberry leaf extract. Our findings demonstrated that MeJA increased antioxidant compounds, mainly anthocyanins, and decreased the viability and migration capacity of AGS cells. In addition, leaf extracts from MeJA-treated plants were also able to decrease the expression of gastric cancer-related proteins. Our outcomes also revealed that the anthocyanin-rich fraction of blueberry leaf extracts showed higher in vitro antiproliferative and anti-invasive effects than the crude leaf extracts. However, it is still uncertain whether the leaf extracts rich in anthocyanins of blueberry plants are capable of exerting a chemopreventive or chemoprotective effect against gastric cancer on an in vivo model. Full article

(This article belongs to the Special Issue Dietary Antioxidants in Cancer Chemoprevention)

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16 pages, 4693 KiB

Open AccessArticle

Endoplasmic Reticulum Stress-Induced Resistance to Doxorubicin Is Reversed by Mulberry Leaf Polyphenol Extract in Hepatocellular Carcinoma through Inhibition of COX-2

by Mon-Yuan Yang, Cheng-Hsun Wu, Tung-Wei Hung and Chau-Jong Wang

Antioxidants 2020, 9(1), 26; https://doi.org/10.3390/antiox9010026 - 26 Dec 2019

Cited by 14 | Viewed by 3913

Abstract

Mulberry (Morus alba L.) leaves are used in Chinese medicine to treat metabolic disorders. Mulberry leaf polyphenol extracts (MLPE) have recently been shown to exhibit anticancer properties. Endoplasmic reticulum (ER) stress represents a pivotal obstacle in solid tumors, resulting in the antiapoptosis [...] Read more.

Mulberry (Morus alba L.) leaves are used in Chinese medicine to treat metabolic disorders. Mulberry leaf polyphenol extracts (MLPE) have recently been shown to exhibit anticancer properties. Endoplasmic reticulum (ER) stress represents a pivotal obstacle in solid tumors, resulting in the antiapoptosis of tumor cells and drug resistance. In this study, pretreatment with the ER stress inducer tunicamycin (TM) attenuated the percentage of apoptosis induced by doxorubicin (DOX). Cotreatment with tunicamycin and MLPE reversed apoptosis induced by DOX. Simultaneously, induction of ER stress with tunicamycin resulted in an increased expression of Cyclooxygenase 2 (COX-2) and Glucose-regulated protein (GRP78) concomitant with the activation of p38 MAPK/PI3K/Akt in HepG2 cells. Furthermore, the suppression of ER stress with celecoxib or p38 MAPK inhibitor successfully recovered DOX-induced apoptosis. Consistent with the inhibition of COX-2 or p38 MAPK, copretreatment with TM and MLPE drastically recovered cytotoxicity and caspase-3 activation in the presence of DOX. These results reveal that MLPE reduces ER stress-induced resistance to DOX in hepatocellular carcinoma (HCC) cells through downregulation of COX-2- or p38 MAPK-mediated PI3K/Akt pathway. Full article

(This article belongs to the Special Issue Dietary Antioxidants in Cancer Chemoprevention)

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14 pages, 3522 KiB

Open AccessArticle

Dietary Antioxidant Trans-Cinnamaldehyde Reduced Visfatin-Induced Breast Cancer Progression: In Vivo and In Vitro Study

by Yi-Fen Chiang, Hsin-Yuan Chen, Ko-Chieh Huang, Po-Han Lin and Shih-Min Hsia

Antioxidants 2019, 8(12), 625; https://doi.org/10.3390/antiox8120625 - 06 Dec 2019

Cited by 22 | Viewed by 3802

Abstract

Excessive growth of cancer cells is the main cause of cancer mortality. Therefore, discovering how to inhibit cancer growth is an important research topic. Recently, the newly discovered adipokine, known as nicotinamide phosphoribosyl transferase (NAMPT, visfatin), which has been associated with metabolic syndrome [...] Read more.

Excessive growth of cancer cells is the main cause of cancer mortality. Therefore, discovering how to inhibit cancer growth is an important research topic. Recently, the newly discovered adipokine, known as nicotinamide phosphoribosyl transferase (NAMPT, visfatin), which has been associated with metabolic syndrome and obesity, has also been found to be a major cause of cancer proliferation. Therefore, inhibition of NAMPT and reduction of Nicotinamide adenine dinucleotide (NAD) synthesis is one strategy for cancer therapy. Cinnamaldehyde (CA), as an antioxidant and anticancer natural compound, may have the ability to inhibit visfatin. The breast cancer cell line and xenograft animal models were treated under different dosages of visfatin combined with CA and FK866 (a visfatin inhibitor) to test for cell toxicity, as well as inhibition of tumor-related proliferation of protein expression. In the breast cancer cell and the xenograft animal model, visfatin significantly increased proliferation-related protein expression, but combination with CA or FK866 significantly reduced visfatin-induced carcinogenic effects. For the first time, a natural compound inhibiting extracellular and intracellular NAMPT has been demonstrated. We hope that, in the future, this can be used as a potential anticancer compound and provide further directions for research. Full article

(This article belongs to the Special Issue Dietary Antioxidants in Cancer Chemoprevention)

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16 pages, 3295 KiB

Open AccessArticle

Dietary Flavonoids Luteolin and Quercetin Inhibit Migration and Invasion of Squamous Carcinoma through Reduction of Src/Stat3/S100A7 Signaling

by Jhen-Jia Fan, Wen-Hsien Hsu, Kuen-Haur Lee, Ku-Chung Chen, Cheng-Wei Lin, Yu-Lin A Lee, Tzu-Ping Ko, Lang-Ta Lee, Ming-Ting Lee, Mau-Sun Chang and Chia-Hsiung Cheng

Antioxidants 2019, 8(11), 557; https://doi.org/10.3390/antiox8110557 - 15 Nov 2019

Cited by 63 | Viewed by 4051

Abstract

Flavonoids are well-known antioxidants and have shown the ability to prevent tumor formation and recurrence. Especially in dietary flavonoids, they have provided convenience and consistence of intake for long-term prevention of tumor formation. Previous reports suggested that S100 calcium-binding protein A7 (S100A7) might [...] Read more.

Flavonoids are well-known antioxidants and have shown the ability to prevent tumor formation and recurrence. Especially in dietary flavonoids, they have provided convenience and consistence of intake for long-term prevention of tumor formation. Previous reports suggested that S100 calcium-binding protein A7 (S100A7) might activate epithelial–mesenchymal transition (EMT) signaling and promote the metastasis of tumor cells; however, the regulatory signaling was unclear. In this study, we found that S100A7 was highly expressed in cancer cells and could be reduced by luteolin (Lu) and quercetin (Qu) through Src/Stat3 signaling. We found that the protein levels of S100A7, phosphorylated Src (p-Src), and p-Stat3 were increased in A431-III cells. Flavonoids Lu and Qu reduce protein levels of p-Src, p-Stat3 and S100A7 in A431-III cells. Treatment of A431-III cells with Src inhibitor SU6656 and Stat3 inhibitor S3I-201 also reduced the protein levels of S100A7. Transactivation activity of 5′-upstream regions of S100A7 was activated by Stat3 but was reduced by treatment with Lu, Qu, SU6656 and S3I-201. The treatment also reduced the migratory and invasive abilities of A431-III cells. In a further analysis of EMT markers, the protein level of E-cad increased and that of Twist decreased after treatment with the inhibitors and flavonoids. Overexpression of S100A7 decreased the protein level of E-cad and increased the Twist level, whereas knockdown of S100A7 had the opposite effects. Treatment with S3I-201, Lu and Qu, compared to the control, were found to decrease metastasis of tumor cells in zebrafish larvae. These results suggest that Lu and Qu may inhibit Src/Stat3/S100A7 signaling to reduce tumorigenesis of cancer cells. Full article

(This article belongs to the Special Issue Dietary Antioxidants in Cancer Chemoprevention)

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15 pages, 1162 KiB

Open AccessArticle

Screening of In Vitro Health Benefits of Tangerine Tomatoes

by Hartono Tanambell, Siew Young Quek and Karen Suzanne Bishop

Antioxidants 2019, 8(7), 230; https://doi.org/10.3390/antiox8070230 - 19 Jul 2019

Cited by 11 | Viewed by 3968

Abstract

Tomatoes have been associated with various health benefits, including the prevention of chronic diseases. The cis-isomers of lycopene occurring in tangerine tomatoes were, through clinical trials, proven to be more bioavailable than the all-trans lycopene found in red tomatoes. Nonetheless, scientific [...] Read more.

Tomatoes have been associated with various health benefits, including the prevention of chronic diseases. The cis-isomers of lycopene occurring in tangerine tomatoes were, through clinical trials, proven to be more bioavailable than the all-trans lycopene found in red tomatoes. Nonetheless, scientific evidence regarding the bioactivities of the tangerine tomatoes is lacking. In this article, the antioxidant, anticancer, and anti-inflammatory properties of extracts prepared from four different tomato varieties, namely Alfred, Olga’s Round Golden Chicken Egg, Golden Green, and Golden Eye, were investigated. While the antioxidant capacities of the extracts were measured through the ferric reducing antioxidant power (FRAP) and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays, their anti-proliferative properties in prostate cancer cell lines were examined through the Sulforhodamine-B (SRB) assay. The anti-inflammatory activities of the extracts were assessed through the toll-like receptor (TLR)2, TLR4, and nucleotide-binding oligomerization domain containing protein 2 (NOD2)-mediated inflammatory pathways. Our results show that the tangerine tomatoes had lower IC50 values in both the anticancer and anti-inflammatory assays compared to the red tomatoes. Specifically, the half-maximal inhibitory concentration (IC50) values of the tangerine tomatoes in LNCaP cells were approximately two to three fold lower than the red tomato (IC50: 14.46, 5.62, and 8.08 mg dry tomato equivalent/mL from Alfred hexane-acetone, Olga’s Round Golden Chicken Egg hexane, and Golden Green hexane, respectively). These findings indicate that the tangerine varieties, Olga’s Round Golden Chicken Egg and Golden Green, possess greater potential to be used in conjunction with treatment and for the prevention of cancer and inflammatory-related diseases than the Alfred (red) and Golden Eye (high beta-carotene) varieties. Full article

(This article belongs to the Special Issue Dietary Antioxidants in Cancer Chemoprevention)

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12 pages, 623 KiB

Open AccessArticle

Assessment of In Vitro Bioactivities of Polysaccharides Isolated from Hericium Novae-Zealandiae

by Zhixia (Grace) Chen, Karen Suzanne Bishop, Hartono Tanambell, Peter Buchanan and Siew Young Quek

Antioxidants 2019, 8(7), 211; https://doi.org/10.3390/antiox8070211 - 08 Jul 2019

Cited by 8 | Viewed by 3652

Abstract

The objective of this study was to investigate the potential effect of the polysaccharides isolated from Hericium novae-zealandiae, a native New Zealand fungus, on the in vitro proliferation of prostate cancer cell lines, gene expression, acetylcholinesterase (AChE) activity, and oxidation. One water-soluble [...] Read more.

The objective of this study was to investigate the potential effect of the polysaccharides isolated from Hericium novae-zealandiae, a native New Zealand fungus, on the in vitro proliferation of prostate cancer cell lines, gene expression, acetylcholinesterase (AChE) activity, and oxidation. One water-soluble and two alkali-soluble polysaccharide fractions were isolated from H. novae-zealandiae. The proliferation of the prostate cancer cell lines DU145, LNCaP, and PC3 was evaluated following treatment with these polysaccharide fractions. It was found that the polysaccharides possess anti-proliferative activity on LNCaP and PC3 cells, with a 50% growth inhibition (IC₅₀) value as low as 0.61 mg/mL in LNCaP. Subsequently, it was determined through via RT-qPCR assay that apoptosis was one of the possible mechanisms responsible for the anti-proliferative activity in LNCaP. This was supported by the up-regulation of CASP3, CASP8, and CASP9. An alternative, discovered in PC3, was revealed to be anti-inflammation, which was hinted at by the down-regulation of IL6 and up-regulation of IL24. The polysaccharides also exhibited antioxidant and weak AChE inhibitory activities. This is the first report on the potential health benefits of polysaccharides prepared from the New Zealand fungus, H. novae-zealandiae. Full article

(This article belongs to the Special Issue Dietary Antioxidants in Cancer Chemoprevention)

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12 pages, 2150 KiB

Open AccessArticle

Novel Docosahexaenoic Acid Ester of Phloridzin Inhibits Proliferation and Triggers Apoptosis in an In Vitro Model of Skin Cancer

by Theodora Mantso, Dimitrios T. Trafalis, Sotiris Botaitis, Rodrigo Franco, Aglaia Pappa, H. P. Vasantha Rupasinghe and Mihalis I. Panayiotidis

Antioxidants 2018, 7(12), 188; https://doi.org/10.3390/antiox7120188 - 11 Dec 2018

Cited by 9 | Viewed by 3924

Abstract

Skin cancer is among the most common cancer types accompanied by rapidly increasing incidence rates, thus making the development of more efficient therapeutic approaches a necessity. Recent studies have revealed the potential role of decosahexaenoic acid ester of phloridzin (PZDHA) in suppressing proliferation [...] Read more.

Skin cancer is among the most common cancer types accompanied by rapidly increasing incidence rates, thus making the development of more efficient therapeutic approaches a necessity. Recent studies have revealed the potential role of decosahexaenoic acid ester of phloridzin (PZDHA) in suppressing proliferation of liver, breast, and blood cancer cell lines. In the present study, we investigated the cytotoxic potential of PZDHA in an in vitro model of skin cancer consisting of melanoma (A375), epidermoid carcinoma (A431), and non-tumorigenic (HaCaT) cell lines. Decosahexaenoic acid ester of phloridzin led to increased cytotoxicity in all cell lines as revealed by cell viability assays. However, growth inhibition and induction of both apoptosis and necrosis was more evident in melanoma (A375) and epidermoid carcinoma (A431) cells, whereas non-tumorigenic keratinocytes (HaCaT) appeared to be more resistant as detected by flow cytometry. More specifically, PZDHA-induced cell cycle growth arrest at the G2/M phase in A375 and A431 cells in contrast to HaCaT cells, which were growth arrested at the G0/G1 phase. Elevated intracellular generation of reactive oxygen species ROS was detected in all cell lines. Overall, our findings support the potential of PZDHA as a novel therapeutic means against human skin cancer. Full article

(This article belongs to the Special Issue Dietary Antioxidants in Cancer Chemoprevention)

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