Anticancer Activity of Essential Oils and Other Extracts from Aromatic Plants Grown in Greece
Abstract
:1. Introduction
2. Methods
3. Results
Family | Species | Extract | Major Components | Collection Location | Type of Cell | Dose/ Concentration | Effect | Ref. |
---|---|---|---|---|---|---|---|---|
Anacard-iaceae | Pistacia lentiscus var. Chia | Essential oil | α-Pinene (67.71%) Myrcene (18.81%) | Commercial | Colon carcinomas Caco2 and HT-29 Mouse colon carcinoma CT-26 | 0.000445–0.89 mg/mL | Caco2 EC50 48 h = 0.0368 ± 0.0225 mg/mL EC50 72 h = 0.0176 ± 0.0035 mg/mL HΤ-29 ΕC50 48 h = 0.1751 ± 0.0028 mg/mL ΕC50 72 h = 0.0762 ± 0.0057 mg/mL CT26 EC50 48 h = 0.1335 ± 0.054 mg/mL ΕC50 72 h = 0.0104 ± 0.0004 mg/mL | [18] |
Colon cancer mouse model (in vivo) | 0.58 g/kg b.w. | 44–52% tumor volume inhibition Cancer cell migration attenuation Downregulation in the expression levels of Ki-67 and survivin | ||||||
Essential oil | α-Pinene (72.93%) Myrcene (13.57%) | Commercial | Ovarian adenocarcinoma 2008 breast adenocarcinoma MCF-7 colon carcinoma LoVo | -- | EC50 > 500 μg/mL | [13] | ||
Essential oil | − | Commercial | chronic myelogenous leukemia K562 Mouse B16 melanoma | 0.01–0.1% v/v | K562: Reduction of viability. Induction of apoptosis; Reduction of VEGF release levels; Inhibition of endothelial cells proliferation and neovascularization; Erk1/2 reduction B16: Reduction of VEGF release levels | [14] | ||
Essential oil | α-Pinene (~70%) | Commercial | Mouse Lewis lung carcinoma | 0.01–0.02% v/v | Cell proliferation suppression; VEGF release reduction; Chemokine release reduction; GTPases Ras, RhoA and NF-κB-dependent reporter gene expression decrease | [16] | ||
Lung cancer mouse model (in vivo) | 45 mg/Kg b.w. | Tumor growth suppression; Apoptosis induction; Neovascularization reduction; Chemokine expression reduction GTPases, Ras, RhoA and NF-κB-dependent reporter gene expression decrease | ||||||
Essential oil | − | − | Mouse Lewis lung carcinoma | 0.01% v/v | PTEN, E2F7, HMOX1 increase; NOD1 decrease; Apoptosis induction; Inflammation decrease | [17] | ||
Essential oil | − | Commercial | Mouse Lewis lung carcinoma | 0.01–0.04% v/v | Reduction of MMP-2, ICAM-1 and VCAM-1 expression levels; attenuation of f-actin fiber formation; limitation of cell invasiveness; impairment of tumor cell adhesive interactions and neovascularization potential | [15] | ||
Mastic gum hexane extract | Caryophyllene | − | Colon carcinoma HCT116 | 25–100 µg/mL | Dose-dependent growth inhibition G1 cell cycle arrest Induction of apoptosis Activation of caspases 3, 8, 9 PARP degradation | [20] | ||
Mastic gum hexane extract | − | − | Colon cancer mouse model (in vivo) | 200 mg/Kg b.w. | Tumor growth suppression | [21] | ||
Mastic gum ethanol extract | − | − | Colon carcinoma HCT116 | 0.2–0.6% v/v | Dose-dependent inhibition of cell growth G1 cell cycle arrest cell death is independent of p53, Bcl-2 and FADD Induction of apoptosis Activation of caspases 3, 8, 9 PARP degradation | [19] | ||
Iridaceae | Crocus sativus L. | Ethanolic extract | trans-crocin 1 (56.4%) trans-crocin 2 (19.2%) cis-crocin 1 (6.8%) | Commercial (Association of Crocus Producers) | Rat glioma C6 | 0.5–10 mg/mL | EC50 = 3 mg/mL No apoptosis induction Colony formation impairment Calpain-dependent cell death, possibly autophagy Synergistic effect with temozolomide at certain combinations | [22] |
Verbena-ceae | Lippia citriodora | Essential oil | Neral (cis-citral) (17.2%) Geranial (trans-citral) (26.4%) | Athens | Hepatocellular carcinoma HepG2 Breast adenocarcinoma MCF-7 Colon adenocarcinoma Caco2 Leukemic monocytes THP-1 Malignant melanoma A375 | 0.64–920 µg/mL | HepG2 EC50 = 74 ± 2.8 μg/mL MCF-7 EC50 = 89 ± 1.4 μg/mL Caco2 EC50 = 71 ± 2.6 μg/mL THP-1 EC50 = 111 ± 3.6 μg/mL A375 EC50 = 9.1 ± 0.6 μg/mL | [23] |
Rutaceae | Citrus medica | Essential oil | Limonene (64.35%) | − | hepatocellular carcinoma HepG2 breast adenocarcinoma MCF-7 colon adenocarcinoma Caco2 Leukemic monocytes THP-1 malignant melanoma A375 immortal keratinocytes HaCat | 0.00063–0.9 mg/mL | HepG2: EC50 = 0.091 ± 0.012 mg/mL MCF-7: EC50 = 0.16 ± 0.012 mg/mL Caco2:EC50 = 0.013 ± 0.00001 mg/mL A375:EC50 = 0.0057 ± 0.0019 mg/mL HaCat:EC50 = 0.024 ± 0.0014 mg/mL | [24] |
Fortunella margarita | Essential oil | Limonene (93.78%) | Corfu Island | hepatocellular carcinoma HepG2 breast adenocarcinoma MCF-7 colon adenocarcinoma Caco2 leukemic monocytes THP-1 | 0.0006–0.86 mg/mL | HepG2 EC50 = n.d. MCF-7 EC50 = n.d. Caco2 EC50 = 0.1 ± 0.027 mg/mL THP-1 EC50 = 0.1 ± 0.0023 mg/mL | [25] | |
Apiaceae | Pimpinella anisum | Essential oil | trans-Anethole (88.13%) | − | 0.00068–0.97 mg/mL | HepG2 EC50 = 0.39 ± 0.0282 mg/mL MCF-7 EC50 = 0.3 ± 0.01 mg/mL Caco2 EC50 = 0.25 ± 0.04 mg/mL THP-1 EC50 =0.11 ± 0.0001 mg/mL | ||
Lamiaceae | Mentha spicata | Essential oil | Carvone (85.41%) | − | 0.00067–0.96 mg/mL | HepG2 EC50 = 0.22 ± 0.038 mg/mL MCF-7 EC50 = 0.284 ± 0.02 mg/mL Caco2 EC50 = 0.162 ± 0.0035 mg/mL THP-1 EC50 = 0.71 ± 0.004 mg/mL | ||
Ocimum basilicum | Essential oil | Methyl chavicol (74.92%) Linalool (18.4) | − | 0.00068–0.98 mg/mL | HepG2 EC50 = 0.18 ± 0.028 mg/mL MCF-7 EC50 = 0.17 ± 0.022 mg/mL Caco2 EC50 = 0.071 ± 0.003 mg/mL THP-1 EC50 =0.67 ± 0.0021 mg/mL | |||
Ethanolic extract | Rosmarinic and caffeic acid | Ioannina | cervix adenocarcinoma HeLa melanoma FemX chronic myelogenous leukaemia K562 ovary adenocarcinoma SKOV3 | 12.5–200 μg/mL | HeLa: EC50 = 164.61 ± 2.58 μg/mL FemX: EC50 = 191.36 ± 2.42 μg/mL K562: EC50 = 157.03 ± 2.25 μg/mL SKOV3: EC50 >200 μg/mL | [26] | ||
Essential oil | Eugenol, Isoeugenol, Linalool | Donation from greenhouse | HeLa: EC50=86.11±0.82 μg/mL FemX: EC50=96.72±0.65 μg/mL K562: EC50=159.78±1.89 μg/mL SKOV3: EC50 >200 μg/mL | |||||
Marrubium thessalum Boiss. & Heldr | Methanolic extract | Mainly Phenylethanoid glycosides and flavonoids | Thessalia | Breast adenocarcinoma MCF-7 cervix adenocarcinoma HeLa Colon carcinoma HCT116 Melanoma FM3 PBMCs | 50–750 μg/mL | MCF-7: EC50 = 417.53 ± 53.4 μg/mL HeLa: EC50 = 218.07 ± 64.1 μg/mL HCT116:EC50 = 474.07 ± 23.14 μg/mL FM3: EC50 = 453.15 ± 37.91 μg/mL 62.20% growth inhibition of PBMCs at 300 μg/mL | [27] | |
Satureja parnassica spp. parnassica | Essential oil | Carvacrol (33.72%) Thymol (17.82%) p-Cymene (10.32%) γ-Terpinene (15.47%) | Mt Parnon, Peloponnese | Breast adenocarcinoma MCF-7 | 0.00000025–0.25% v/v | EC50 = 0.08 ± 0.03% v/v | [28] | |
Satureja thymbra | Carvacrol (39.1%) Thymol (12.59%) p-Cymene (8.83%) γ-Terpinene (10.61%) | Mt Immitos, Attiki | EC50 = 0.002 ± 0.00038% | |||||
Origanum vulgare sub. hirtum | Essential oil | Carvacrol (79.58%) | Euboea | Larynx carcinoma Hep-2 Cervix adenocarcinoma HeLa African green monkey kidney Vero Rabbit skin RSC | -- | Complete cell death in all cell lines at 0.0001% v/v Reduction of Vero viability at 0.00002% v/v (EC50 = 0.000027% v/v) | [29] | |
Origanum Onites L | Essential oil | Carvacrol (48%) | Northern Greece | Hepatocellular carcinoma HepG2 Breast adenocarcinoma MCF-7 Colon adenocarcinoma HT-29 Malignant melanoma A375 Mouse colon carcinoma CT-26 | 0.0000589–0.842 mg/mL | EC50 48 h HT-29: 58.00 ± 0.70 µg/mL CT26: 71.70 ± 1.20 µg/mL EC50 72 h A375: 8.90 ± 0.70 µg/mL MCF-7: 10.00 ± 1.70 µg/mL HepG2: 23.00 ± 4.20 µg/mL HT-29: 0.35 ± 0.20 µg/mL CT26: 1.10 ± 0.30 µg/mL Attenuation of colon cancer cell migration Induction of Apoptosis-Related Morphological Changes | [30] | |
Colon cancer mouse model (in vivo) | 0.370 g/kg b.w | 52% lower mean tumor volume | ||||||
Hyperi-caceae | Origanum dictamnus (dittany) | Essential oil | Carvacrol (52.18%) γ-terpinene (8.4%) | Crete | Hepatocellular carcinoma HepG2 | 0.00007–0.1% v/v | EC50 = 0.0069 ± 0.00014% v/v | [31] |
Essential oil | p-cymene (32.7%) γ-terpinene (12.4%) | Crete | Colon carcinoma LoVo Hepatocellular carcinoma HepG2 | 2.5–100 µg/mL | LoVo: EC50 24 h = 84.76 ± 1.03 μg/mL EC50 48 h = 72.26 ± 1.05 μg/mL HepG2: Reduction of cell viability | [32] | ||
Dichloromethane residue | Ursolic acid | Crete | Mouse leukemia P-388 Non-small cell lung carcinoma NSCLC-N6 | -- | P-388: EC50 = 8 μg/mL NSCLC-N6: EC50 = 14 μg/mL | [33] | ||
Ethanolic extract | − | Almost inactive | ||||||
Infusion | Carvacrol 3745.3 μg/cup (200 mL) Rosmarinic acid 7244 | Crete | Colon carcinoma HT-29 Prostate adenocarcinoma PC-3 | 0.2, 0.6, 1 μg/μL | PC3 antiproliferative activity: Origanum dictamnus >marjoram>sage> rosemary>St John’s wort>thyme HT-29 antiproliferative activity: Origanum dictamnus >rosemary> thyme>sage>marjoram>St John’s wort IL-8 decrease in HT-29: sage> Origanum dictamnus >thyme> marjoram>St John’ s wort> rosemary IL-8 decrease in PC-3: Thyme>sage > Origanum dictamnus >marjoram > rosemary> St John’s wort Reduced levels of the p65 NF-kB subunit by St John’s Wort in HT29 and thyme in PC3 | [34] | ||
Rosmarinus officinalis (rosemary) | Rosmarinic acid 669 Carvacrol 362.3 | |||||||
Thymus Vulgaris (thyme) | Carvacrol 182,138 Thymol 80,655 | |||||||
Origanum majorana (marjoram) | Rosmarinic acid 9674.4 Carvacrol 2796 | |||||||
Salvia officinalis (sage) | Rosmarinic acid 8082.7 Carvacrol 3745 | |||||||
Hypericum perforatum (St John’s Wort) | Epicatechin 29,275.4 Catechin 3448.2 Quercetin 3134 | Central Macedonia | ||||||
Methanolic extract | Hypericin hyperforin | Wild collected 38/15, 41/15: North-West Macedonia 43/15: North–Central Macedonia | Colon adenocarcinoma Caco2 | 0.01–100 μg/mL | 38/15 & 41/15: Did not affect cell viability 43/15: Reduced viability to 82.04% only at the highest concentration | [35] | ||
Cultivated NAT, D-4: North Greece | NAT: Reduced viability to 41.14% only at the highest concentration D-4: Did not affect cell viability | |||||||
Aqueous solution (AS) | − | Ioannina | Urinary bladder carcinoma T24 Rat urinary bladder carcinoma NBT-II | AS and MS: 0.63-20 μL/mL ME: 13-40 μg/mL PEE: 2–12 μg/mL | T24:AS EC50 = 4.7 μL/mL MS EC50 = 1.1 μL/mL ME EC50 = 18 μg/mL PEE EC50 = 5 μg/mL NBT-II: ME EC50 = 13 μg/mL PEE EC50 = 7 μg/mL Indication of apoptosis induction in T24 and NBT-II cells by PEE extract | [36] | ||
Methanolic solution (MS) | − | |||||||
Methanolic extract (ME) | Hyperforin (7.62%) | |||||||
Petroleum ether extract (PEE) | Hyperforin (18.9%) | |||||||
Methanolic extract | − | Monodendrι, Epirus | Colon carcinoma Caco2 Hepatocellular carcinoma HepG2 | 10–100 mg/mL | EC50 of all extracts against all cell cancer lines > 100 mg/mL, apart from: H. empetrifolium Wild Parnitha: Caco2 EC50 = 51.3 mg/mL HepG2 EC50 = 43.7 mg/mL H. empetrifolium Wild Hymettus: Caco2 EC50 = 54.2 mg/mL HepG2 EC50 = 45.8 mg/mL H. empetrifolium Wild Parnon: Caco2 EC50 = 29 mg/mL HepG2 EC50 = 25.1 mg/mL | [37] | ||
Hypericumempetrifolium Wild | − | Mt. Parnitha, Attiki Mt.Hymettos, Attiki Parnon, Arkadia | ||||||
Hypericum rumeliacum Boiss. | − | Mt. Parnassos, Viotia | ||||||
Hypericum perfoliatum L. | − | Korinthos Preveza | ||||||
Hypericum triquetrifolium Turra | − | Rafina, Attiki Lakonia Crete | ||||||
Lamiaceae | Teucrium brevifolium | Essential oil | Spathulenol (9%) δ-cadinene (4.2%) | Karpathos Island | Lung carcinoma COR-L23 Colorectal adenocarcinoma Caco2 Amelanotic melanoma C32 | 5–200 μg/mL | COR-L23: EC50 = 80.7 ± 2.1μg/mL Caco2: EC50 = 164 ± 2.1 μg/mL C32: EC50 >200 μg/mL | [38] |
Teucrium flavum | Essential oil | caryophyllene (12.2%) 4-vinyl guaiacol (9.7%) caryophyllene oxide (7.9%) | Pelion mountain | COR-L23: EC50 = 104 ± 2.1 μg/mL Caco2: EC50 >200 μg/mL C32: EC50 >200 μg/mL | ||||
Teucrium montbretii ssp. heliotropiifolim | Essential oil | Carvacrol (13.9%) caryophyllene oxide (12.7%) | Karpathos Island | COR-L23: EC50 = 143 ± 2.1 μg/mL Caco2: EC50 = 92.2 ± 2.1 μg/mL C32: EC50 = 135 ± 2.1 μg/mL | ||||
Teucrium polium ssp. capitatum | Essential oil | Carvacrol (10.1%), caryophyllene (9.8%) torreyol (7.6%) | Crete | COR-L23: EC50 = 104 ± 2.1 μg/mL Caco2: EC50 = 52.7 ± 2.1 μg/mL C32: EC50 = 91.2 ± 2.1 μg/mL | ||||
Asteraceae | Matriacaria chamomilla (chamomile) | infusion | Carvacrol 9321.5 μg/cup (200 mL) Chlorogenic acid 4800.34 | Crete | Colon carcinoma HT-29 Prostate adenocarcinoma PC-3 | 0.2, 0.6, 1 μg/μL | HT-29: Pink savory most effective, chamomile least cytotoxic PC-3: Pink savory most effective, chamomile and mountain tea least cytotoxic IL-8 decrease in HT-29: mountain tea > pennyroyal > chamomile > Origanum microphyllum > pink savory> Origanum vulgare IL-8 decrease in PC-3: Origanum microphyllum > pennyroyal > pink savory > Origanum vulgare > chamomile > mountain tea Reduction of p65 NF-kB subunit only by chamomile in HT-29 cells | [39] |
Lamiaceae | Origanum microphyllum | Carvacrol 23,274 | ||||||
Sideritis syriaca (mountain tea) | Carvacrol 1220 Chlorogenic acid 828.49 | |||||||
Origanum vulgare | Carvacrol 177,855 Thymol 2545 | |||||||
Satureja thymbra (pink savory) | Carvacrol 87,814 Thymol 34,382 | |||||||
Mentha pulegium (pennyroyal) | Carvacrol 3755 Thymol 1727 | |||||||
- | Lesvos Island | Breast adenocarcinoma MCF-7 Colon carcinoma Caco2 Hepatocellular carcinoma HepG2 Normal mouse adipose areolar cells | 10–100 μg/mL | EC50 of all extracts against all cell cancer lines > 75 μg/mL, apart from: Clinopodium vulgare: MCF-7 EC50 = 60.4 μg/mL Rosmarinus officinalis: MCF-7 EC50 = 42.6 μg/mL Thymus parnassicus Halácsy: Caco2 EC50 = 44.6 μg/mL HepG2 EC50 = 50.3 μg/mL MCF-7 EC50 = 54.7 μg/mL Rosmarinus officinalis was the most cytotoxic against a normal mouse adipose arelar cell lines at 100 μg/mL | [40] | |||
Micromeria juliana (L.) Bentham ex Reinchenb. | Methanolic extract | - | Mt Parnassos, Viotia | |||||
Nepeta argolica Bory et Chaub. subsp. argolica | - | Mt. Parnitha, Attiki | ||||||
Phlomis pungens Willd. | - | Mt Parnassos, Viotia | ||||||
Rosmarinus officinalis L. | - | Zante Island | ||||||
Satureja graeca L | - | Mt. Penteli, Attiki | ||||||
Scutellaria rupestris Boiss. & Heldr | - | Mt. Parnitha, Attiki | ||||||
Sideritis sipylea Boiss | - | Lesvos Island | ||||||
Stachys spruneri Boiss. | - | Mt. Parnitha, Attiki | ||||||
- | Mt. Pateras, Attiki | |||||||
Teucrium divaricatum Heldr. ssp. divaricatum | - | Mt.- Pateras, Attiki | ||||||
Teucrium polium L. | - | Mt.Hymettus, Attiki | ||||||
Thymus atticus Celak. | - | Mt. Parnitha, Attiki | ||||||
Thymus longicaulis C. Presl | - | Trikala | ||||||
Thymus parnassicus Halacsy | - | Mt. Kitheron, Attiki | ||||||
Thymus samius Ronniger & Rech | - | Samos Island | ||||||
Thymus teucrioides Boiss. & Spruner | - | Domokos, Fthiotida | ||||||
Clinopodium vulgare L | - | Mt. Parnitha, Attiki | ||||||
Lavandula stoechas L. | - | Lesvos Island |
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Fitsiou, E.; Pappa, A. Anticancer Activity of Essential Oils and Other Extracts from Aromatic Plants Grown in Greece. Antioxidants 2019, 8, 290. https://doi.org/10.3390/antiox8080290
Fitsiou E, Pappa A. Anticancer Activity of Essential Oils and Other Extracts from Aromatic Plants Grown in Greece. Antioxidants. 2019; 8(8):290. https://doi.org/10.3390/antiox8080290
Chicago/Turabian StyleFitsiou, Eleni, and Aglaia Pappa. 2019. "Anticancer Activity of Essential Oils and Other Extracts from Aromatic Plants Grown in Greece" Antioxidants 8, no. 8: 290. https://doi.org/10.3390/antiox8080290