Promising Anticancer Potential of Herbal Compounds against Breast Cancer: A Systemic Review


  • R.K. University, School of Pharmacy, Rajkot, Gujarat, 360020, India


Breast cancer (BC) exhibit a high level of mortality rate and incidence but a comprehensive treatment is unavailable, which can successfully eradicate this fatal disease. Novel therapeutic strategies have been intensively studied to eradicate BC, including the use of traditional medicines and phytochemical (herbal compounds). These compounds have been studied in many aspects, such as targeting cell cycle and key tumor-associated metabolic pathways. In this study, we reviewed the literature for the potential therapeutic application of herbal compounds against breast cancer. Several terms, including “Herbal compoundsâ€, “Breast Cancer†and “Traditional medicinesâ€, were searched in PubMed and Web of Science databases. The search results were narrowed down using many filters and the resultant literature was critically analyzed. The enormous number of articles showed the promising potential of herbal compounds as anticancer therapy. The comprehensive evaluation of the literature suggested the anti-angiogenic, anti-proliferative, anticancer stem cells, anti-inflammatory/antioxidant, anti-metastatic, and epigenetic effects of herbal compounds as anticancer effects against BC. Despite this enormous data, there is lack of sufficient demonstration of the consumption of herbal compounds in a regular as anticancer strategy in clinical trials. Therefore, given its promising anticancer potential, focus should be shifted towards the regular use of herbal compounds in anticancer strategies.


Anticancer Strategy, Breast Cancer, Herbal Compounds, Traditional Medicines

Subject Discipline

Pharmacology and cancer

Full Text:


Golubnitschaja O, Debald M, Yeghiazaryan K, Kuhn W, Pesˇta M, Costigliola V, et al. Breast cancer epide micin the early 21st century: evaluation of risk factors, cumulative questionnaires and recommendations for preventive measures. Tumor Biol. 2016;37(10):1294112957. PMid:27448308.

Liu RH. Dietary bioactive compounds and their health implications. J Food Sci 2013;78(s1):A18-A25. PMid:23789932.

Liu RH. Health-promoting components of fruits and vegetables in the diet. Adv Nutr. 2013;4(3):384S-392S. PMid:236748 08 PMCid:PMC3650511.

Yiannakopoulou EC. Effect of green tea catechins on breast carcinogenesis: a systematic review of in-vitro and in-vivo experimental studies. Eur J Cancer Prev. 2014;23(2):84-89. 328364f23e. PMid:23939462.

Kapinova A, Stefanicka P, Kubatka P, Zubor P, Uramova S, Kello M, et al. Are plant-based functional foods better choice against cancer than single phyto chemicals? A critical review of current breast cancer research. BiomedPharmacother. 2017;96:1465-1477. PMid:2 9198744.

Kulkarni AD, Sundaresan A, Rashid MJ, Yamamoto S, Karkow F. Application of diet-derived taste active components for clinical nutrition: perspectives from ancient Ayurvedic medical science, space medicine, and modern clinical nutrition. Curr Pharm Des. 2014;20(16):2791-2796. 6128113199990571. PMid:23886389.

Wang CY, Bai XY, Wang CH. Traditional Chinese medicine: a treasured natural resource of anticancer drug research and development. Am J Chin Med. 2014;42(03):543-559. S0192415X14500359. PMid:24871650.

Singletary K, MacDonald C, Wallig M. Inhibition by rosemary and carnosol of 7,12dimethylbenz [a] anthracene (DMBA)-induced rat mammary tumor igenesis and in vivo DMBA-DNA adduct forma-tion. Cancer Lett. 1996;104(1):43-48. 16/0304-3835(96)04227-9.

Jeyabalan J, Aqil F, Munagala R, Annamalai L, Vadhanam MV, Gupta RC. Chemopreventive and therapeuticactivity of dietaryblueberry against estrogen-mediated breast cancer. J Agric Food Chem. 2014;62(18):3963-3971. 734j. PMid:24245576 PMCid:PMC4334276.

Adams LS, Kanaya N, Phung S, Liu Z, Chen S. Whole blueberry powder modulates growth and metastasis of MDA-MB-231 triple negative breast tumors in nude mice. J Nutr. 2011;141(10):1805-1812. PMid:21880954 PMC id:PMC3174855.

Ravoori S, Vadhanam MV, Aqil F, Gupta RC. Inhibition of estrogen-mediated mammary tumorigenesis by blueberry and black raspberry. J Agric Food Chem. 2012;60(22):5547-5555. PMid:22571764.

Mandal A, Bishayee A. Mechanism of breast cancer preventive action of pomegranate: disruption of estrogen receptor and Wnt/β-catenin signaling pathways. Molecules. 2015;20(12):22315-22328. PMid:2 6703530 PMCid:PMC6332439.

Bishayee A, Mandal A, Bhattacharyya P, Bhatia D. Pomegranate exerts chemoprevention of experi mentally induced mammary tumorigenesis by suppression of cell proliferation and induction of apoptosis. Nutr Cancer. 2015;68(1):120-130. PMid:2669 9876 PMCid:PMC4784500.

Nassan MA, Soliman MM, Ismail SA, El-Shazly SA. Effect of Taraxacumofficinale extract on PI3K/Akt pathway in DMBA induced breast cancer in albino rats. Biosci Rep. 2018;38(6). BSR20180334. PMid:30126855 PMCid:PMC6435453.

Kubatka P, Kapinová A, Kružliak P, Kello M, Výbohová D, Kajo K, et al. Antineoplastic effects of Chlorella pyrenoidosa in the breast cancer model. Nutrition. 2015; 31(4):560-569. PMid:25770318.

Kubatka P, Kello M, Kajo K, Kruzliak P, Výbohová D, Smejkal K, et al. Young barley indicates antitumor effects in experimental breast cancer in vivo and in vitro. Nutr Cancer. 2016;68(4):611-621. PMid:27042893.

Kubatka P, Kapinová A, Kello M, Kruzliak P, Kajo K, Výbohová D. et al, Fruit peel polyphenols demonstrate substantial anti-tumour effects in the model of breast cancer. Eur J Nutr. 2016;55(3):955-965. PMid:25930965.

Kubatka P, Kello M, Kajo K, Kruzliak P, Výbohová D, Mojžiš J, et al., Oregano demonstrates distinct tumour-suppressive effects in the breast carcinoma model. Eur J Nutr. 2017;56(3):1303-1316. PMid:26907089.

Kubatka, P., Uramova, S., Kello, M., Kajo, K., Kruzliak, P., Mojzis, J., et al., Antineoplastic effects of clove buds (Syzygiumaromaticum L.) in the model of breast carcinoma. J Cell Mol Med. 2017;21(11):2837-2851. PMid:28524540 PMCid:PMC5661249.

Liu X, Lv K. Cruciferous vegetables intake is inversely associated with risk of breast cancer: a meta-analysis. Breast. 2013;22(3):309-313. PMid:22877795.

Fung TT, Chiuve SE, WillettWC, Hankinson SE, Hu FB, Holmes MD. Intake of specific fruits and vegetables in relation to risk of estrogen receptor-negative breast cancer among postmenopausal women. Breast Cancer Res Treat. 2013;138(3):925-930. https://doi. org/10.1007/s10549-013-2484-3. PMid:23532538 PM Cid:PMC3641647.

Butler LM, Wu AH, Wang R, Koh WP, Yuan JM, Yu MC. A vegetable-fruit-soy dietary pattern protects against breast cancer among postmenopausal Singapore Chinese women. Am J Clin Nutr. 2010;91(4):10131019. PM id:20181808 PMCid:PMC2844682.

Ko KP, Kim SW, Ma SH, Park B, Ahn Y, Lee JW, et al. Dietary intake and breast cancer among carriers and noncarriers of BRCA mutations in the Korean Hereditary Breast Cancer Study. Am J Clin Nutr. 2013; 98(6):1493-1501. 12.057760. PMid:24153343.

Li M, Tse LA, Chan WC, Kwok CH, Leung SL, Wu C, et al. Evaluation of breast cancer risk associated with tea consumption by menopausal and estrogen receptor status among Chinese women in Hong Kong. Cancer Epidemiol. 2016;40:73-78. PMid:26680603 PMCid:PMC671 9777.

Kumar N, Titus-Ernstoff L, Newcomb PA, Tren tham-Dietz A, Anic G, Egan KM. Tea consumption and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2009;18(1):341-345. PMid:1912451 8 PMCid:PMC3156033.

Sangaramoorthy M, Koo J, John EM. Intake of bean fiber, beans, and grains and reduced risk of hormone receptor-negative breast cancer: The San Francisco Bay Area Breast Cancer Study. Cancer Med. 2018; 7(5):2131-2144. PMid:29573201 PMCid:PMC5943543.

Pourzand A, Tajaddini A, Pirouzpanah S, AsghariJafarabadi M, Samadi N, Ostadrahimi AR, et al. Associations between dietary allium vegetables and risk of breast cancer: a hospital-based matched case-control study. Breast Cancer. 2016;19(3), 292-300. PMid:27721879 PMC id:PMC5053314.

Castello' A, Polla'n M, Buijsse B, Ruiz A, Casas AM, Baena-CanËœada JM, et al. Spanish Mediter-ranean diet and other dietary patterns and breast cancer risk: Case-control EpiGEICAM study. Br J Cancer. 2014; 111(7):1454-1462. PMid:25101568 PMCid:PMC4183855.

Cottet V, Touvier M, Fournier A, Touillaud MS, Lafay L, Clavel-Chapelon F, et al. Postmenopausal breast cancer risk and dietary patterns in the E3N-EPIC prospective cohort study. Am J Epidemiol. 2009; 170(10):12571267. PMid:1982 8509.

Bahadoran Z, Mirmiran P, Azizi F. Dietary polyphenols as potential nutraceuticals in management of diabetes: A review. J Diabetes MetabDisord. 2013;12(1):43. PMid:2393 8049.

Baglietto L, Krishnan K, Severi G, Hodge A, Brinkman M, English DR, et al. Dietary patterns and risk of breast cancer. Br J Cancer. 2011;104(3):524-31. PMid:21157446 PMCid: PMC3049555.

Rugo H, Shtivelman E, Perez A, Vogel C, Franco S, Tan Chiu E, et al. Phase I trial and antitumor effects of BZL101 for patients with advanced breast cancer. Breast Cancer Res Treat. 2007;105(1):17-28. https:// PMid:17111207.

Perez AT, Arun B, Tripathy D, Tagliaferri MA, Shaw HS, Kimmick GG, et al. A phase 1B dose escalation trial of Scutellariabarbata (BZL101) for patients with metastatic breast cancer. Breast Cancer Res Treat. 2010;120(1):111-118. s10549-009-0678-5. PMid:20054647.

Mao Y, Hao J, Jin ZQ, Niu YY, Yang X, Liu D, et al. Network pharmacology-based and clinically relevant prediction of the active ingredients and potential targets of Chinese herbs in metastatic breast cancer patients. Oncotarget. 2017;8(16):27007-27021. PMid:28212580 PM Cid:PMC5432314.

Manni A, Richie JP, Schetter SE, Calcagnotto A, Trushin N, Aliaga C, et al. Stearoyl-CoA desaturase-1, a novel target of omega-3 fatty acids for reducing breast cancer risk in obese postmenopausal women.

Eur J ClinNutr. 2017; 71(6):762-765. PMid:28145413.

Zou M, Xu C, Li H, Zhang X, Fan W. 3,3'-Diindoly lmethane suppresses ovarian cancer cell viability and metastasis and enhances chemotherapy sensitivity via STAT3 and Akt signaling in vitro and in vivo. Arch BiochemBiophys. 2018; S0003-9861(18):3008730090.

Park S, Cho DH, Andera L, Suh N, Kim I. Curcumin enhances TRAIL-induced apoptosis of breast cancer cells by regulating apoptosis-related proteins. Mol Cell Biochem. 2013;383(1-2):39-48. PMid:23846485.

Manouchehri JM, Turner KA, Kalafatis M. TRAILInduced Apoptosis in TRAIL-Resistant Breast Carcinoma Through Quercet in Cotreatment. Breast Cancer (Auckl). 2018;12:1-12. PMid:29434473 PMCid:P MC5802616.

Tseng HS, Wang YF, Tzeng YM, Chen DR, Liao YF, Chiu HY, et al. Aloe-Emodin Enhances Tamoxifen Cytotoxicity by Suppressing Ras/ERK and PI3K/mTOR in Breast Cancer Cells. Am J Chin Med.

;45(2):337-350. 5X17500215. PMid:28231748.

Diaz-Chavez J, Fonseca-Sanchez MA, ArechagaOcampo E, Flores-Perez A, Palacios-Rodriguez Y, Dominguez-Gomez G, et al. Proteomic profiling reveals that resveratrol inhibits HSP27 expression and sensitizes breast cancer cells to doxorubicin therapy. PLoS One. 2013;8(5):e64378. journal.pone.0064378. PMid:23724044 PMCid:PMC 3664632.

Ito Y, Mitani T, Harada N, Isayama A, Tanimori S, Takenaka S, et al. Identification of carbonyl reductase 1 as a resveratrol-binding protein by affinity chromatography using 4'-amino-3,5-dihydroxy-trans-stilbene. J Nutr Sci Vitaminol (Tokyo). 2013; 59(4):358-364. PMid:24064738.

Richards CE, Vellanki SH, Smith YE, Hopkins AM. Diterpenoid natural compound C4 (Crassin) exerts cytostatic effects on triple-negative breast cancer cells via a pathway involving reactive oxygen species. Cell Oncol (Dordr). 2018; 41(1):35-46. PMid:29134467.

Di Y, De Silva F, Krol ES, Alcorn J. Flaxseed Lignans Enhance the Cytotoxicity of Chemotherapeutic Agents against Breast Cancer Cell Lines MDA-MB-231 and SKBR3. Nutr Cancer. 2018; 70(2):306-315. PMid:29303360.

Mundhe NA, Kumar P, Ahmed S, Jamdade V, Mundhe S, Lahkar M. Nordihydroguaiaretic acid ameliorates cisplatin induced nephrotoxicity and potentiates its anti-tumor activity in DMBA induced breast cancer in female Sprague-Dawley rats. Int. Immunopharmacol. 2015; 28(1):634-642. PMid:26247680.

Hanušová V, Caltová K, Svobodová H, Ambrož M, Skarka A, Murínová N et al. The effects of β-caryophyllene oxide and trans -nerolidol on the efficacy of doxorubicin in breast cancer cells and breast tumor-bearing mice. Biomed Pharmacother. 2017;95:828-836. 17.09.008. PMid:28903178.

Zhong Y, Zhang F, Sun Z, Zhou W, Li ZY, You QD, et al. Drug resistance associates with activation of Nrf2 in MCF-7/DOX cells, and wogonin reverses it by downregulating Nrf2-mediated cellular defense response. MolCarcinog. 2013; 52(10):824-834. PMid:22593043.

Zhang S, Sagawa K, Arnold RD, Tseng E, Wang X, Morris ME. Interactions between the flavonoid biochanin A and P-glycoprotein substrates in rats: In vitro and in vivo. J Pharm Sci. 2010;99(1):430-441. PMid:19499569.

Qian J, Xia M, Liu W, Li L, Yang J, Mei Y, et al. Glabr idinresensitizes p-glycoprotein-overexpressing multi drug-resistant cancer cells to conventional chemo therapeutic agents. Eur J Pharmacol. 2019;852:231243. PM id:30959046.

Zong L, Cheng G, Liu S, Pi Z, Liu Z, Song F. Reversal of multidrug resistance in breast cancer cells by a combination of ursolic acid with doxorubicin. J Pharm Biomed Anal. 2019;165:268-275. PMid:30572191.

Louisa M, Soediro TM, Suyatna FD. In vitro modulation of P-glycoprotein, MRP-1 and BCRP expression by mangiferin in doxorubicin-treated MCF-7 cells. Asian Pac J Cancer Prev. 2014; 15(4):1639-1642. PMid:24641 381.

Li YH, Niu YB, Sun Y, Zhang F, Liu CX, Fan L, Mei QB. Role of phytochemicals in colorectal cancer prevention. World J Gastroenterol. 2015;21(31):92629272. PM id:26309353 PMCid:PMC4541379.

Geng Y, Zhou Y, Wu S, Hu Y, Lin K, Wang Y, et al. Sulforaphane induced apoptosis via promotion of mitochondrial fusion and ERK1/2-mediated 26S proteasome degrada-tion of novel pro-survival bim and upregulation of bax in human non-small cell lung cancer cells. J Cancer. 2017;8(13):2456-2470. PMid:28900483 PMCid:P MC5595075.

Singh SK, Banerjee S, Acosta EP, Lillard JW, Singh R. Resveratrol induces cell cycle arrest and apoptosis with docetaxel in prostate cancer cells via a p53/ p21WAF1/CIP1 and p27KIP1 pathway. Oncotarget. 2017;8(10):17216-17228. oncotarget.15303. PMid:28212547 PMCid:PMC53700 34.

Agarwal A, Kasinathan A, Ganesan R, Balasub ramanian A, Bhaskaran J, Suresh S, et al. Curcumin induces apoptosis and cell cycle arrest via the activation of reactive oxygen species-independent mitochondrial apoptotic pathway in Smad4 and p53 mutated colon adenocarcinoma HT29 cells.

Nutr Res. 2018;51:67-81. PMid:29673545.

Zhang Y, Chen S, Wei C, Rankin GO, Ye X, Chen YC. Flavonoids from Chinese bayberry leaves induced apoptosis and G1 cell cycle arrest via Erk pathway in ovarian cancer cells. Eur J Med Chem. 2018; 147:218226. PMid:29438890 PMCid:PMC5823286.

Sabarwal A, Agarwal R, Singh RP. Fisetin inhibits cellular proliferation and induces mitochondria-dependent apoptosis in human gastric cancer cells. MolCar cinog. 2017;56(2):499-514. PMid:27254419.

Cheng YM, Tsai CC, Hsu YC. Sulforaphane, a dietary isothiocyanate, induces G2/M arrest in cervical cancer cells through cyclinB1 downregulation and GADD45 β/CDC2 association. Int J MolSci. 2016;17(9):1530. PMid:276264 12 PMCid:PMC5037805.

Zhang L, Cheng X, Gao Y, Bao J, Guan H, Lu R, et al. Induction of ROS-independent DNA damage by curcumin leads to G2/M cell cycle arrest and apoptosis in human papillary thyroid carcinoma BCPAP cells. Food Funct. 2016;7(1):315-325. PMid:26442630.

Jeong JW, Park S, Park C, Chang YC, Moon DO, Kim SO, et al. N-benzyl-N-methyldecan-1-amine, a phenylamine derivative isolated from garlic cloves, induces G2/M phase arrest and apoptosis in U937 human leukemia cells. Oncol Rep. 2014;32(10):373381. PMid:248 59825.

Zhang Z, Wang CZ, Du GJ, Qi LW, Calway T, He TC, et al. Genistein induces G2/M cell cycle arrest and apoptosis via ATM/p53-dependent pathway in human colon cancer cells. Int J Oncol. 2013;43(1):289296. PMid:236 86257 PMCid:PMC3742162.

Chikara S, Nagaprashantha LD, Singhal J, Horne D, Awasthi S, Singhal SS. Oxidative stress and dietary phytochemicals: role in cancer chemoprevention and treatment. Cancer Lett. 2018;413:122-134. PMid:29113871.

Hwang KA, Choi KC. Anticarcinogenic effects of dietary phytoestrogens and their chemopreven-tive mechanisms. Nutr Cancer. 2015; 67(5):796-803.


Lou M, Zhang LN, Ji PG, Feng FQ, Liu JH, Yang C, et al. Quercetin nanoparticles induced autophagy and apoptosis through AKT/ERK/Caspase-3 signaling pathway in human neuro-glioma cells: in vitro and in vivo. Biomed Pharmacother. 2016;84:1-9. PMid:27621033.

Okubo S, Uto T, Goto A, Tanaka H, Nishioku T, Yamada K, et al. Berberine induces apoptotic cell death via activation of caspase-3 and-8 in HL-60 human leukemia cells: nuclear local-ization and structure-acti vity relationships. Am J Chin Med. 2017;45(7):14971511.


Yang Y, Wang T, Chen D, Ma Q, Zheng Y, Liao S, et al. Quercetin preferentially induces apoptosis in KRASmutant colorectal cancer cells via JNK signaling pathways. Cell Biol 2018;43(2):117-124. PMid:30203888.

Satonaka H, Ishida K, Takai M, Koide R, Shigemasa R, Ueyama J, et al. (-)-Epigallocatechin-3-gallate downregulates doxorubicin-induced overexpres-sion of P-glycoprotein through the coordinate inhibition of PI3K/Akt and MEK/ERK signaling path-ways. Anticancer Res. 2017; 37(11):6071-6077.

Alrawaiq N, Abdullah A. Dietary phytochemicals activate the redox-sensitive transcription factor Nrf2. Int J Pharm PharmSci. 2014;6:11-16.

Chen JC, Hsieh MC, Lin SH, Lin CC, Hsi YT, Lo YS, et al. Coronarin D induces reactive oxygen speciesmediated cell death in human nasopharyngeal cancer cells through inhibition of p38 MAPK and activation of JNK. Oncotarget. 2017;8(64):108006108019.

PMid:29296219 PMCid:PMC5746121.

Chen XX, Lam KH, Chen QX, Leung GP, Tang SCW, Sze SC, et al. Ficusvirensproanthocyanidins induced apoptosis in breast cancer cells concomitantly ameliorated 5-fluorouracil induced intestinal mucositis in rats. Food ChemToxicol. 2017;110:49-61. PMid:2903 0256.

Azqueta A, Collins A. Polyphenols and DNA damage: A mixed blessing. Nutrients. 2016;8(12):785. PMid:27918471 PMCid:PMC5188440.

Mirossay L, Varinska, L, Mojzˇisˇ J. Antiangiogenic effect of flavonoids and chalcones: an update. Int J MolSci. 2017; 19(1):27. ijms19010027. PMid:29271940 PMCid:PMC5795978.

Mojzis J, Varinska L, Mojzisova G, Kostova I, Mirossay L. Antiangiogenic effects of flavonoids and chalcones. Pharmacol Res. 2008;57(4):259-265. PMid:18387817.

Wong JC, Fiscus RR. Resveratrol at anti-angiogenesis/ anticancer concentrations suppresses pro-tein kinase G signaling and decreases IAPs expression in HUVECs. Anticancer Res. 2015; 35(1):273-281.

Varinska L, Mirossay L, Mojzisova G, Mojzis J. Antiangogenic effect of selected phytochemicals.

Pharmazie. 2010;65(1):57-63.

Varinska L, Kubatka P, Mojzis J, Zulli A, Gazdikova K, Zubor P, et al. Angio-modulators in cancer therapy: new perspectives. Biomed. Pharmacother. 2017;89:578590. PM id:28258040.

Park SY, Lee HE, Li H, Shipitsin M, Gelman R, Polyak K. Heterogeneity for stemcell-related markers according to tumor subtype and histologic stage in breast cancer. Clin Cancer Res. 2010;16(3):876-887. PMid:20103682 PMCid:PMC2818503.

Klonisch T, Wiechec E, Hombach-Klonisch S, Ande SR, Wesselborg S, Schulze-Osthoff K, et al. Cancer stem cellmarkers in common cancers-therapeutic implications. Trends Mol Med. 2008;14(10):450460. PMid:18775674.

Choi HS, Kim SL, Kim JH, Deng, HY, Yun BS, Lee DS. Triterpene Acid (3-O-p-coumaroyltormentic acid) isolated from aronia extracts inhibits breast cancerstem cell formation through downregulation of c-myc protein. Int J MolSci. 2018;19(9):25-28. PMid:30149665 PMCid:PMC6164992.

Soltanian S, Riahirad H, Pabarja A, Jafari E, Khandani BK. Effect of Cinnamic acid and FOLFOX in diminishing side population and downregulating cancer stem cell markers in colon cancer cell line HT-29. DARU. 2018;26(1):19-29. PMid:30209760 PMCid:PMC6154487.

Aliebrahimi S, Kouhsari SM, Arab SS, Shadboorestan A, Ostad SN. Phytochemicals, witha-ferin A and carnosol, overcome pancreatic cancer stem cells as c-Met inhibitors. Biomed Pharmacother. 2018;106:1527-1536. a.2018.07.055. PMid:30119228.

Hermawan A, Putri H. Current report of natural product development against breast cancer stem cells. Int J Biochem Cell Biol. 2018;104:114-132. PMid:30266524.

Khan S, Shukla S, Sinha S, Meeran SM. Epigenetic targets in cancer and aging: dietary and therapeutic interventions. Expert OpinTher Targets. 2016;20(6):689-703. 2.2016.1132702. PMid:26667209.

Uramova S, Kubatka P, Dankova Z, Kapinova A, Zolakova B, Samec M, et al. Plant natural modulators in breast cancer prevention: status quo and future perspectives reinforced by predictive, preventive and personalised medical approach. EPMA J. 2018;9(4):403-419. PMid:30538792 PMCid:PMC6261910.

Dagdemir A, Durif J, Ngollo M, Bignon YJ, BernardGallon D. Histone lysine trimethylation or acetylation can be modulated by phytoestrogen, estrogen or antiHDAC in breast cancer cell lines. Epigenomics. 2013; 5(1):51-63. PMid:2 3414320.

Attoub S, Hassan AH, Vanhoecke B, Iratni R, Takahashi T, Gaben AM, et al. Inhibition of cell survival, invasion, tumor growth and histone deacetylase activity by the dietary flavonoid luteolin in human epithelioid cancer cells. Eur J Pharmacol. 2011;651(1-3):18-25. PMid:21074525.

Ng JM, Yu J. Promoter hypermethylation of tumour suppressor genes as potential biomarkers in colorectal cancer Int J MolSci. 2015;16(2):2472-2496. PMid:25622259 PMCid:P MC4346847.

Abu-Serie MM, Habashy NH, Attia WE. In vitro evaluation of the synergistic antioxidant and antiinflammatory activities of the combined extracts from Malaysian Ganodermalucidum and Egyptian Chlorella vulgaris. BMC Complement Altern Med. 2018;18(1):154. PMid:29747629 PMCid:PMC5946467.

Jayshree A, Jayashree S, Thangaraju N. Chlorella vulgaris and Chlamydomonasreinhardtii: effective antioxidant, antibacterial and anticancer mediators. Indian J Pharm Sci. 2016;78:575-581.

Kunte M, Desai K. The protein extract of Chlorella minutissima inhibits the expression of MMP1, MMP-2 and MMP-9 in cancer cells through upregulation of TIMP-3 and down regulation of c-Jun. Cell J. 2018;20(2):211-219.

Meng TX, Irino N, Kondo R. Melanin biosynthesis inhibitory activity of a compound isolated from young green barley (Hordeumvulgare L.) in B16 melanoma cells. J Nat Med. 2015;69(3):427-431. https://doi.

org/10.1007/s11418-015-0902-z. PMid:25827948.

Czerwonka A. Kawka K. Cykier K. Lemieszek MK, Rzeski W. Evaluation of anticancer activity of water and juice extracts of young Hordeumvulgare in human cancer cell lines HT-29 and A549. Ann Agric Environ Med. 2017;24(2):345-349. PMid:28664721.

Fang YAO, Zhang JY, Xiang XIAO, Ying DONG, Zhou XH. Antitumor activities and apoptosis-regulated mechanisms of fermented barley extract in the transplantation tumor model of human HT-29 cells in nude mice. Biomed Environ Sci. 2017;30(1):10-21.

Woo SM, Kwon SC, Ko SG, Cho SG. Barley grass extract causes apoptosis of cancer cells by increasing intracellular reactive oxygen species production. Biomed Rep. 2017;6(6):681-685. PMid:28584641 PMCid:PM C5449973.

VaÅ¡ko L, VaÅ¡ková J, FejerÄáková A, MojžiÅ¡ová G, PoráÄová J. Comparison of some antioxidant properties of plant extracts from Origanumvulgare, Salvia officinalis, Eleutherococcussenticosus and Stevia rebaudiana. In Vitro Cell Dev BiolAnim. 2014;50(7):614-622. PMid:24737278.

Zhang XL, Guo YS, Wang CH, Li GQ, Xu JJ, Chung HY, et al. Phenolic compounds from Origanumvulgare and their antioxidant and antiviral activities. Food Chem. 2014;152:300-306. PMid:24444941.

Rubin B, Manso J, Monticelli H, Bertazza L, Redaelli M, Sensi F, et al. Crude extract of Origanumvulgare L. induced cell death and suppressed MAPK and PI3/ Akt signaling pathways in SW13 and H295R cell lines. Nat Prod Res. 2019;33(11):1646-1649. PMid:29334260.

Makrane H, El Messaoudi M, Melhaoui A, El Mzibri M, Benbacer L, Aziz M. Cytotoxicity of the aqueous extract and organic fractions from Origanummajorana on human breast cell line MDA-MB-231 and human colon cell line HT-29. Adv Pharmacol Sci. 2018; 2018:3297193. PMid:30210537 PMCid:P MC6126111.

Al Dhaheri Y, Eid A, AbuQamar S, Attoub S, Khasawneh M, Aiche G, et al. Mitotic arrest and apoptosis in breast cancer cells induced by Origanum majorana extract: upregulation of TNF-α and down regulation of survivin and mutant p53. PLoS One. 2013;8(2):e56649. ne.0056649. PMid:23451065 PMCid:PMC3579842.

Al Dhaheri Y, Attoub S, Arafat K, Abuqamar S, Viallet J, Saleh A, et al. Anti-metastatic and anti-tumor growth effects of Origanummajorana on highly metastatic human breast cancer cells: inhi-bition of NFκB signaling and reduction of nitric oxide production. PLoS One. 2013;8(7):e68808. PMid:23874773 PMCid:PMC3707896.

Cortés-Rojas DF, de Souza CR, Oliveira WP. Clove (Syzygiumaromaticum): A precious spice. Asian Pac J Trop Biomed. 2014;4(2):90-96.

Dwivedi V, Shrivastava R, Hussain S, Ganguly C, Bharadwaj M. Comparative anticancer poten-tial of clove (Syzygiumaromaticum)--an Indian spiceagainst cancer cell lines of various anatomical origin. Asian Pac J Cancer Prev. 2011;12(8):1989-1993.

Aisha AF, Abu-Salah KM, Alrokayan SA, Siddiqui MJ, Ismail Z, Majid AM. Syzygiumaromaticum extracts as good source of betulinic acid and potential anti-breast cancer. Rev Bras Farmacogn. 2012;22(2):335-343.

Pilátová M, Stupáková V, Varinská L, Sarisský M, Mirossay L, Mirossay A, et al. Effect of selected flavones on cancer and endothelial cells. Gen Physiol Biophys. 2010;29(2):134-43. 0.4149/gpb_2010_02_134. PMid:20577025.

Kim MY, Bo HH, Choi EO, Kwon DH, Kim HJ, Ahn KI, et al. Induction of apoptosis by Citrus unshiu peel in human breast cancer MCF-7 cells: Involvement of ROS-dependent activation of AMPK. Biol Pharm Bull. 2018;41(5):713-721. b.b17-00898. PMid:29709909.

Kello M, Kulikova L, Vaskova J, Nagyova A, Mojzis J. Fruit peel polyphenolic extract-induced apoptosis in human breast cancer cells is associated with ROS production and modulation of p38MAPK/ Erk1/2 and the Akt signaling pathway. Nutr Cancer. 2017;69(6):920-931. 81.2017.1339819. PMid:28718669.

Shanmugapriya, Chen Y, Kanwar JR, Sasidharan S. Anticancer activity and molecular mechanism of polyphenol rich calophylluminophyllum fruit extract in MCF-7 breast cancer cells. Nutr Cancer. 2017;69(8):1308-1324. 5581.2017.1367944. PMid:29068745.

Hirsch K, Danilenko M, Giat J, Miron T, Rabinkov A, Wilchek M, et al. Effect of purified allicin, the major ingredient of freshly crushed garlic, on cancer cell proliferation. Nutr Cancer. 2000;38(2):245254. PMid:11525603.

El Khalki L, Tilaoui M, Jaafari A, Ait Mouse H, Zyad A. Studies on the dual cytotoxicity and anti-oxidant properties of Berberis vulgaris extracts and its main constituent berberine. Adv Pharmacol Sci. 2018; 2018: 3018498. PM id:29805448 PMCid:PMC5817274.

Haba R, Watanabe S, Wada M, Udaka S. Effects of lactoferrin, soya germ and polyamine on 2-amino1-methyl-6-phenylimidazo [4,5-b]-pyridine(PhIP)induced breast carcinogenesis in rats. Biofactors. 2004;22(1-4):127-31. 20220125. PMid:15630267.

Oyenihi OR, Krygsman A, Verhoog N, de Beer D, Saayman MJ, Mouton TM, et al. Chemoprevention of LA7-induced mammary tumor growth by SM6Met, a well-characterized Cyclopia extract. Front Pharmacol. 2018;9:650. PMid:29973879 PMCid:PMC6019492.

Li J, Liu X, Chen H, Sun Z, Chen H, Wang L, et al. Multi-targeting chemoprevention of Chinese herb formula YangheHuayan decoction on experimentally induced mammary tumorigenesis. BMC Complement Altern Med. 2019;19(1):48. PMid:30760265 PMCid:PMC6373088.