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Current Cancer Therapy Reviews


ISSN (Print): 1573-3947
ISSN (Online): 1875-6301

Review Article

Recent Advances of Novel Therapeutic Agents from Botanicals for Prevention and Therapy of Breast Cancer: An Updated Review

Author(s): Namrata Singh, Poonam Kushwaha*, Amresh Gupta and Om Prakash

Volume 16 , Issue 1 , 2020

Page: [5 - 18] Pages: 14

DOI: 10.2174/1573394715666181129101502

Price: $65


Breast cancer is among the foremost common malignancies and the second leading cause for cancer-related deaths in females. Varied treatment approaches are projected to cause a subject matter reduction in the fatality rate. Carcinoma treatment is highly challenging due to therapeutic resistance and reoccurrence. Several studies have revealed that bioactive compounds isolated from natural products such as plants, vegetables, and marine origins have a therapeutic and preventive role in breast carcinoma. Utilization of these bioactive agents in amelioration of cancer as complementary and alternative therapy increases day by day due to growing scientific shreds of evidence of the biomedical innovation and clinical trials. Due to the safe nature of these photochemical investigators are focusing on the investigation of lead compounds from traditional herbal medicine to discover new lead anticancer agents in the single pure compound. This review highlights the mechanism of action and future prospects of novel medicinal agents from botanical sources that have chemoprevention activity against breast carcinoma together with other types of body cancer. The major bioactive, which are used as a remedy for the prevention and treatment of breast cancer, is summarized and explored here.

Keywords: Breast cancer, chemotherapy, natural products, anticancer agents, carcinogenesis, carcinoma.

Graphical Abstract
World health organization. Media center: Cancer. Available from: (Accessed on: 23 April 2018)
Mitra S, Dash R. Natural products for the management and prevention of breast cancer. Evid Based Complement Alternat Med 2018; 20188324696
Doyle LA, Yang W, Abruzzo LV, et al. A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci USA 1998; 95(26): 15665-70.
Ullah MF. Cancer multidrug resistance (MDR): A major impediment to effective chemotherapy. APJCP 2008; 9(1): 1-6.
Eliyatkin N, Yalcin N, Zengel B, Aktaş S, Vardar E. Molecular classification of breast carcinoma: from traditional, old-fashioned way to a new age. J Breast Health 2015; 11(2): 59-66.
Esteva FJ, Gutiérrez C. Nonepithelial Malignancies of the Breast. In: Harris JR, Lippman ME, Morrow M, Osborne CK, Eds. Diseases of the Breast. 5th ed. Lippincott-Williams & Wilkins: Philadelphia, PA 2014.
Tromberg BJ, Shah N, Lanning R, et al. Non-invasive in vivo characterization of breast tumors using photon migration spectroscopy. Neoplasia 2000; 2(1-2): 26-40.
Sandra M. Swain. Ductal carcinoma in situ. Cancer Invest 1992; 10(5): 443-54.
Van Zee KJ, White J, Morrow M, Harris JR. Ductal carcinoma in situ and microinvasive carcinoma. In: Harris JR, Lippman ME, Morrow M, Osborne CK, Eds. Diseases of the Breast. 5th ed. Lippincott-Williams & Wilkins: Philadelphia, PA 2014.
Haagensen CD, Lane N, Lattes R, Bodian C. Lobular neoplasia (so called lobular carcinoma in situ) of the breast. Cancer 1978; 42: 737-69.
Afonso N, Bouwman D. Lobular carcinoma in situ. Eur J Cancer Prev 2008; 17(4): 312-6.
Salvadori B, Cusumano F, Del BR, et al. Surgical treatment of phyllodes tumors of the breast. Cancer 1989; 63: 2532-6.
Calhoun KE, Allison KH, Kim JN, et al. Phyllodes tumors. In: Harris JR, Lippman ME, Morrow M, Osborne CK, Eds. Diseases of the breast. 5th ed. Lippincott-Williams & Wilkins: Philadelphia, PA 2014.
Jensen RA, Page DL, Dupont WD, Rogers LW. Invasive breast cancer risk in women with sclerosing adenosis. Cancer 1983; 64(10): 1977-83.
Visscher DW, Nassar A, Degnim AC, et al. Sclerosing adenosis and risk of breast cancer. Breast Cancer Res Treat 2014; 144: 205-12.
Carter D. Intraductal papillary tumors of the breast. A study of 78 cases. Cancer 1977; 39(4): 1689-92.
Ohuchi N, Abe R, Kasai K. Possible cancerous change of intraductal papillomas of the breast. A 3- D reconstruction study of 25 cases. Cancer 1984; 54: 605-11.
Das D, Panda SK, Jena B, Sahoo AK. Somatic cell count: A biomarker for early diagnosis and therapeutic evaluation in bovine mastitis. IJCMAS 2018; 7(3): 1459-63.
Jahanfar S, Jenn NGC, Lieng TC. Antibiotics for mastitis in breastfeeding women. Sao Paulo Med J 2018; 134(1): 273.
Haagensen CD. Mammary‐duct ectasia. A disease that may simulate carcinoma. Cancer 1951; 4(4): 749-61.
Dixon JM. Periductal mastitis/duct ectasia. World J Surg 1989; 13(6): 715-20.
Dillon DA, Guidi AJ, Schnitt SJ. Pathology of invasive breast cancer. In: Harris JR, Lippman ME, Morrow M, Osborne CK, Eds. Diseases of the breast. 5th ed. Lippincott-Williams & Wilkins: Philadelphia, PA 2014.
Almutlaq BA, Almuazzi RF, Almuhayfir AA, et al. Breast cancer in Saudi Arabia and its possible risk factors. J Cancer Policy 2017; 12: 83-9.
National breast cancer foundation, INC. Media center: Risk factors. Available from: (Assessed on: 30 May 2018)
Lynch BM, Neilson HK, Friedenreich CM. Physical activity and breast cancer prevention. Recent Results Cancer Res 2011; 186: 13-42.
Chowdhury R, Sinha B, Sankar MJ. Breastfeeding and maternal health outcomes: A systematic review and meta-analysis. Acta Paediatr 2015; 104(467): 96-113.
Collaborative Group on Hormonal Factors in Breast Cancer. Menarche, menopause, and breast cancer risk: Individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies. Lancet Oncol 2012; 13(11): 1141-51.
Hortobagyi GN. Treatment of breast cancer. N Engl J Med 1998; 339(14): 974-84.
Maughan KL, Lutterbie MA, Ham PS. Treatment of breast cancer. Am Fam Physician 2010; 81(11): 1339-46.
Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: Role of ATP-dependent transporters. Nat Rev Cancer 2002; 2(1): 48-58.
Fumoleau P, Largillier R, Clippe C. Multicentre, phase II study evaluating capecitabine monotherapy in patients with anthracycline- and taxane-pretreated metastatic breast cancer. Eur J Cancer 2004; 40(4): 536-42.
Love RR, Leventhal H, Easterling DV, Nerenz DR. Side effects and emotional distress during cancer chemotherapy. Cancer 1989; 63(3): 604-12.
Bishayee A, Sethi G. Bioactive natural products in cancer prevention and therapy: Progress and promise. Semin Cancer Biol 2016; 40-41: 1-3.
Mehta RG, Murillo G, Naithani R, Peng X. Cancer chemoprevention by natural products: How far have we come? Pharm Res 2010; 27(6): 950-61.
Wang H, Khor TO, Shu L, et al. Plants against cancer: A review on natural phytochemicals in preventing and treating cancers and their druggability. Anticancer Agents Med Chem 2012; 12(10): 1281-305.
Mondal S, Bandyopadhyay S, Ghosh MK, Mukhopadhyay S, Roy S, Mandal C. Natural products: Promising resources for cancer drug discovery. Anticancer Agents Med Chem 2012; 12(1): 49-75.
Rane R, Karpoormath R. Discovery and development of new anticancer drugs inspired from natural product leads, Part 2. Anticancer Agents Med Chem 2015; 15(8): 932.
Seca AML, Pinto DCGA. Plant secondary metabolites as anticancer agents: Successes in clinical trials and therapeutic application. Int J Mol Sci 2018; 19(1): 263.
Zhang L, Hung MC, Chang CJ, Bacus SS. Suppressed transformation and induced differentiation of HER2/neu-overexpressing breast cancer cells by emodin. Cancer Res 1995; 55(17): 3890-6.
Kawiak A, Zawacka PJ, Lojkowska E. Plumbagin induces apoptosis in Her2-overexpressing breast cancer cells through the mitochondrial-mediated pathway. J Nat Prod 2012; 75(4): 747-51.
Wang Y, Gho WM, Chan FL, Chen S, Leung LK. The red clover (Trifolium pratense) isoflavone biochanin A inhibits aromatase activity and expression. Br J Nutr 2008; 99(2): 303-10.
Kim HY, Choi TW, Kim HJ, et al. A methylene chloride fraction of Saururus chinensis induces apoptosis through the activation of caspase-3 in prostate and breast cancer cells. Phytomedicine 2011; 18: 567-74.
Bae HB, Li M, Son JK, et al. Sauchinone, a lignan from Saururus chinensis, reduces tumor necrosis factor-alpha production through the inhibition of c-raf/MEK1/2/ ERK 1/2 pathway activation. Int Immunopharmacol 2010; 10: 1022-8.
Kim ES, Jeong CS, Moon A. Genipin, a constituent of Gardenia jasminoides Ellis, induces apoptosis and inhibits invasion in MDA-MB-231 breast cancer cells. Oncol Rep 2012; 27: 567-72.
Pons DG, Nadal-Serrano M, Torrens-Mas M, Valle A, Oliver J, Roca P. UCP2 inhibition sensitizes breast cancer cells to therapeutic agents by increasing oxidative stress. Free Radic Biol Med 2015; 86: 67-77.
Lee JS, Lee MS, Oh WK, Sul JY. Fatty acid synthase inhibition by amentoflavone induces apoptosis and antiproliferation in human breast cancer cells. Biol Pharm Bull 2009; 32(8): 1427-32.
Monteiro R, Faria A, Azevedo I, Calhau C. Modulation of breast cancer cell survival by aromatase inhibiting hop (Humulus lupulus L.) flavonoids. J Steroid Biochem Mol Biol 2007; 105(1-5): 124-30.
Ko EY, Moon A. Natural products for chemoprevention of breast cancer. J Cancer Prevent 2015; 20(4): 223-31.
Choudhuri T, Pal S, Agwarwal ML, Das T, Sa G. Curcumin induces apoptosis in human breast cancer cells through p53-dependent Bax induction. FEBS Lett 2002; 512: 1-3. 334-40.
Takeshima M, Ono M, Higuchi T, Chen C, Hara T, Nakano S. Anti-proliferative and apoptosis-inducing activity of lycopene against three subtypes of human breast cancer cell lines. Cancer Sci 2014; 105(3): 252-7.
Miller PE, Snyder DC. Phytochemicals and cancer risk: A review of the epidemiological evidence. Nutr Clin Pract 2012; 27(5): 599-612.
Lau TY, Leung LK. Soya isofavones suppress phorbol 12-myristate 13-acetate-induced COX-2 expression in MCF-7 cells. Brit J Nutrition 2006; 96(1): 169-76.
Li Y, Zhang T, Korkaya H. Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells. Clin Cancer Res 2010; 16(9): 2580-90.
Sinha D, Sarkar N, Biswas J, Bishayee A. Resveratrol for breast cancer prevention and therapy: Preclinical evidence and molecular mechanisms. Semin Cancer Biol 2016; 40-41: 209-23.
Andreani C, Bartolacci C, Wijnant K, et al. Resveratrol fuels HER2 and ERα-positive breast cancer behaving as proteasome inhibitor. Aging (Albany NY) 2017; 9(2): 508-20.
Moongkarndi P, Kosem N, Kaslungka S, Luanratana O, Pongpan N, Neungton N. Antiproliferation, antioxidation and induction of apoptosis by Garcinia mangostana (mangosteen) on SKBR3 human breast cancer cell line. J Ethnopharmacol 2017; 90(1): 161-6.
Zhang Y, Qian RQ, Li PP. Shikonin, an ingredient of Lithospermum erythrorhizon, down-regulates the expression of steroid sulfatase genes in breast cancer cells. Cancer Lett 2009; 284(1): 47-54.
Siriwarin B, Weerapreeyakul N. Seasamaol induced apoptotic effect in lung adenocarcinoma cells through both intrinsic and extrinsic pathways. Chembiol Interact 2016; 254: 109-16.
Kakkar V, Kaur IP. Preparation, charecerization and scale up of sesamol loaded solid lipid nanopartic. Nanotechnol Develop 2012; 2(1): 2-e8.
Vaya J, Tamir S. The relation between the chemical structure of flavonoids and their estrogen like activities. Curr Med Chem 2004; 11: 1333-43.
Peralta EA, Murphy LL, Minnis J, Louis S, Dunnington GL. American ginseng inhibits induced COX-2 and NFKB activation in breast cancer cells. J Surg Res 2009; 157(2): 261-7.
Li JS, Wang WJ, Sun Y, Zhang YH, Zheng L. Ursolic acid inhibits the development of nonalcoholic fatty liver disease by attenuating endoplasmic reticulum stress. Food Funct 2015; 6: 1643-51.
Kim KH, Seo HS, Choi HS, Choi I, Shin YC, Ko SG. Induction of apoptotic cell death by ursolic acid through mitochondrial death pathway and extrinsic death receptor pathway in MDA-MB-231 cells. Arch Pharm Res 2011; 34: 1363-72.
Yeh CT, Wu CH, Yen GC. Ursolic acid, a naturally occurring triterpenoid, suppresses migration and invasion of human breast cancer cells by modulating c-Jun N-terminal kinase, Akt and mammalian target of rapamycin signaling. Mol Nutr Food Res 2010; 54: 1285-95.
Liu Z, Zhang B, Liu Ding Z, Hu X. Schisandrin B attenuates cancer invasion and metastasis via inhibiting epithelial-mesenchymal transition. Plos one 2012; 7(7) e40480
Nobili S, Landini I, Giglioni B, Mini E. Pharmacological strategies for overcoming multidrug resistance. Curr Drug Targets 2006; 7: 861-79.
Patil JB, Kim J, Jayaprakasha GK. Berberine induces apoptosis in breast cancer cells (MCF-7) through mitochondrial-dependent pathway. Eur J Pharmacol 2010; 645(1-3): 70-80.
Lee SK, Cui B, Mehta RR, Kinghorn AD, Pezzuto JM. Cytostatic mechanism and antitumor potential of novel 1H-cyclopenta (b) benzofuran lignans isolated from Aglaia elliptica. Chem Biol Interact 1998; 115: 215-28.
Bhui K, Tyagi S, Prakash B, Shukla Y. Pineapple bromelain induces autophagy, facilitating apoptotic response in mammary carcinoma cells. Biofactors 2010; 36(6): 474-82.
Dhandayuthapani S, Perez HD, Paroulek A, et al. Bromelain-induced apoptosis in GI-101A breast cancer cells. J Med Food 2012; 15(4): 344-9.
Ma G, Tabanca N, Baser KHC, et al. Inhibition of NF-kappaB-mediated transcription and induction of apoptosis in human breast cancer cells by epoxypseudoisoeugenol-2-methyl butyrate. Cancer Chemother Pharmacol 2009; 63(4): 673-80.
Lin YJ, Hou YC, Lin CH. Puerariae radix isoflavones and their metabolites inhibit growth and induce apoptosis in breast cancer cells. Biochem Biophys Res Commun 2009; 378(4): 683-8.
Hien TT, Kim HG, Han EH, Kang KW, Jeong HG. Molecular mechanism of suppression of MDR1 by puerarin from Pueraria lobata via NF-kappaB pathway and cAMP-responsive element transcriptional activity-dependent up-regulation of AMP-activated protein kinase in breast cancer MCF-7/adr cells. Mol Nutr Food Res 2010; 54(7): 918-28.
Degner SC, Papoutsis AJ, Selmin O, Romagnolo DF. Targeting of aryl hydrocarbon receptor-mediated activation of cyclooxygenase-2 expression by the indole-3-carbinol metabolite 3, 3′-diindolylmethane in breast cancer cells. J Nutr 2009; 139(1): 26-32.
Belguise K, Guo S, Sonenshein GE. Activation of FOXO3a by green tea polyphenol epigallocatechin-3-gallate induces estrogen receptor alpha expression reversing invasive phenotype of breast cancer cells. Cancer Res 2007; 67(12): 5763-70.
Zhang G, Wang Y, Zhang Y, et al. Anti-cancer activities of tea epigallocatechin-3-gallate in breast cancer patients under radiotherapy. Curr Mol Med 2012; 12(2): 163-76.
Farabegoli F, Papi A, Bartolini G, Ostan R, Orlandi M. (-)-Epigallocatechin-3-gallate downregulates Pg-P and BCRP in a tamoxifen resistant MCF-7 cell line. Phytomedicine 2010; 17(5): 356-62.
Filomeni G, Aquilano K, Rotilio G, Ciriolo MR. Reactive oxygen species-dependent c-Jun NH2-terminal kinase/c-Jun signaling cascade mediates neuroblastoma cell death induced by diallyl disulfide. Cancer Res 2003; 63(18): 5940-9.
Wang YB, Qin J, Zheng XY, Bai Y, Yang K, Xie LP. Diallyl trisulfide induces Bcl-2 and caspase-3-dependent apoptosis via downregulation of Akt phosphorylation in human T24 bladder cancer cells. Phytomedicine 2010; 17(5): 363-8.
Malki A, El-Saadani M, Sultan AS. Garlic constituent diallyl trisulfide induced apoptosis in MCF7 human breast cancer cells. Cancer Biol Ther 2009; 8(22): 2175-85.
Liu Y, Zhu P, Wang Y, et al. Antimetastatic therapies of the polysulfide diallyl trisulfide against triple-negative breast cancer (TNBC) via suppressing MMP2/9 by blocking NF-κB and ERK/MAPK signaling pathways. Plos One 2015; 10(4) e0123781
Hahm ER, Singh SV. Diallyl trisulfide inhibits estrogen receptor-α activity in human breast cancer cell. Breast Cancer Res Treat 2014; 144(1): 47-57.
Malki A, El-Saadani M, Sultan AS. Garlic constituent diallyl trisulfide induced apoptosis in MCF7 human breast cancer cells. Cancer Biol Ther 2009; 8(22): 2175-85.
Lee CC, Liu KJ, Wu YC, Lin SJ, Chang CC, Huang TS. Sesamin inhibits macrophage-induced vascular endothelial growth factor and matrix metalloproteinase-9 expression and proangiogenic activity in breast cancer cells. Inflammation 2011; 34(3): 209-21.
Chakraborty A, Gupta N, Ghosh K, Roy P. In vitro evaluation of the cytotoxic, anti-proliferative and anti-oxidant properties of pterostilbene isolated from Pterocarpus marsupium. Toxicol Invitro 2010; 24(4): 1215-28.
Casado P, Villar PZ, Carlos EDV, Campa M, Lazo PS, Ramos S. Vincristine regulates the phosphorylation of the antiapoptotic protein HSP27 in breast cancer cells. Cancer Lett 2007; 247(2): 273-82.
Oh M, Choi YH, Choi S, et al. Anti-proliferating effects of ginsenoside Rh2 on MCF-7 human breast cancer cells. Int J Oncol 1999; 14(5): 869-75.
Kim SJ, Kim AK. Anti-breast cancer activity of Fine Black ginseng (Panax ginseng Meyer) and ginsenoside Rg5. J Ginseng Res 2015; 39(2): 125-34.
Kim S, Moon A. Capsaicin-induced apoptosis of H-ras-transformed human breast epithelial cells is Rac-dependent via ROS generation. Arch Pharm Res 2004; 27: 845-9.
Thoennissen NH, O’Kelly J, Lu D, et al. Capsaicin causes cell-cycle arrest and apoptosis in ER-positive and -negative breast cancer cells by modulating the EGFR/HER-2 pathway. Oncogene 2010; 29: 285-96.
Shim Y, Song JM. Quantum dot nanoprobe-based high-content monitoring of notch pathway inhibition of breast cancer stemcell by capsaicin. Mol Cell Probes 2015; 29(6): 376-81.
Hsieh CJ, Kuo PL, Hsu YC, Huang YF, Tsai EM, Hsu YL. Arctigenin, a dietary phytoestrogen, induces apoptosis of estrogen receptor-negative breast cancer cells through the ROS/p38 MAPK pathway and epigenetic regulation. Free Radic Biol Med 2014; 67: 159-70.
Ci Y, Zhang Y, Liu Y, et al. Myricetin suppresses breast cancer metastasis through down regulating the activity of matrix metalloproteinase (MMP)-2/9. Pytother Res 2018; 32(7): 1373-81.
Lee CJ, Wilson L, Jordan MA, Nguyen V, Tang J, Smiyun G. Hesperidin suppressed proliferations of both human breast cancer and androgen-dependent prostate cancer cells. Phytother Res 2010; 24(Suppl. 1): S15-9.
Knickle A, Fernando W, Greenshields AL, et al. Myricetin-induced apoptosis of triple-negative breast cancer cells is mediated by the iron-dependent generation of reactive oxygen species from hydrogen peroxide. Food Chem Toxicol 2018; 118: 154-67.
Crown J, O’Leary M, Ooi WS. Docetaxel and paclitaxel in the treatment of breast cancer: A rewiew of clinical experience. Oncologist 2004; 9(2): 24-32.
Stumm S, Meyer A, Lindner M, Bastert G, Wallwiener D, Gückel B. Paclitaxel treatment of breast cancer cell lines modulates Fas/Fas ligand expression and induces apoptosis which can be inhibited through the CD40 receptor. Oncology 2004; 66(2): 101-11.
Bernard SA, Ayorinde O. Search for a novel antioxidant, antiinflammatory/analgesic or anti-proliferative drug: Cucurbitacins hold the ace. J Med Plants Res 2010; 4(25): 2821-6.
Cencic R, Carrier M, Vázquez GG, et al. Antitumor activity and mechanism of action of the cyclopenta(b)benzofuran, silvestrol. PLoS One 2009; 4(4)e5223
Akcakanat A, Hong DS, Bernstam FM. Targeting translation initiation in breast cancer. Translation (Austin) 2014; 2(1)e28968
Harmon AW, Patel YM. Naringenin inhibits glucose uptake in MCF-7 breast cancer cells: A mechanism for impaired cellular proliferation. Breast Cancer Res Treat 2004; 85: 103-10.
Ramos J, Hatkevich T, Eanes L, Sanchez IS, Patel YM. Naringenin inhibits proliferation and survival of tamoxifen-resistant breast cancer cells. IntechOpen: UK 2017; pp. 541-56.
Xue JP, Wang G, Zhao ZB, Wang Q, Shi Y. Synergistic cytotoxic efect of genistein and doxorubicin on drug-resistant human breast cancer MCF-7/Adr cells. Oncol Reports 2014; 32(4): 1647-53.
McGuire KP, Ngoubilly N, Neavyn M, Jacoby SL. 3, 3-Diindolylmethane and paclitaxel act synergistically to promote apoptosis in HER2/Neu human breast cancer cells. J Surg Res 2006; 132(2): 208-13.
Kars MD, Iseri OD, Gunduz U, Ural AU, Arpaci F, Molnar J. Development of rational in-vitro models for drug resistance in breast cancer and modulation of MDR by selected compounds. Anticancer Res 2006; 26(6): 4559-68.
Prakash O, Kumar A, Kumar P. Anticancer potential of plants and natural products: A review. Am J Pharmacol Sci 2013; 1: 104-15.

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