Therapeutic Strategies of Natural Agents on Triple-Negative Breast Cancer

  • Ashok Kumar PanduranganEmail author
  • Mohd Rais Mustafa


Triple-negative breast cancers (TNBC) are described as a human breast cancer subtype that does not express estrogen receptor (ER) and progesterone receptor (PR), and they lack overexpression and/or lack gene amplification of human epidermal growth factor receptor 2 (HER2). TNBC are highly aggressive, and they are present among 10–15% of all breast cancer subtypes which constitute about 80% of all basal-like tumours. Plants produce diverse number of organic compounds. Traditionally these natural products are known as secondary metabolites or phytometabolites. Bioactive natural products’ chemical structure and function have been studied since the 1850s. Comprehending these chemical structure and functions led to recognition of their biological properties as anticancer drugs. Among phytometabolites, phytoestrogens have been widely studied as a chemopreventive and chemotherapeutic agent due to their high affinity to interact with estrogen receptors. However, TNBC are indifferent to hormonal therapy, they became a therapeutic hurdle. The only systemic therapy currently left is chemotherapy which often fails due to ability of TNBC to develop resistance to chemotherapeutic drugs. Therefore, different theories exist, which suggest focusing on drugs that target TNBC survival-dependent molecular pathways instead. For instance, several studies reported TNBC depend on NF-κB to survive and avoid apoptosis. The aim of this chapter is to discuss the various bioactive natural products extracted from various parts of plants and mushrooms showing potential inhibitory effect against TNBC.


Chemotherapy Hormonal receptors Natural products Molecular pathway Triple-negative breast cancer 



We are thankful to Dr. Yamini Chandramohan, Centre for Biotechnology, Anna University, Chennai, India, for her critical comments to improve the quality of the manuscript.


  1. Ahmad FB, Holdsworth D (1995) Traditional medicinal plants of Sabah, Malaysia part III. The Rungus people of Kudat. Int J Pharmacogn 33:262–264CrossRefGoogle Scholar
  2. Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, Damanhouri ZA, Anwar F (2013) A review on therapeutic potential of Nigella sativa: a miracle herb. Asian Pac J Trop Biomed 3:337–352CrossRefPubMedPubMedCentralGoogle Scholar
  3. Ahn EM, Bang MH, Song MC, Park MH, Kim HY, Kwon BM, Baek NI (2006) Cytotoxic and ACAT-inhibitory sesquiterpene lactones from the root of Ixeris dentata forma albiflora. Arch Pharma Res 29:937–941CrossRefGoogle Scholar
  4. Ananda Sadagopan SK, Mohebali N, Looi CY, Hasanpourghadi M, Pandurangan AK, Arya A, Karimian H, Mustafa MR (2015) Forkhead box transcription factor (FOXO3a) mediates the cytotoxic effect of vernodalin in vitro and inhibits the breast tumor growth in vivo. J Exp Clin Cancer Res 34:147CrossRefPubMedPubMedCentralGoogle Scholar
  5. Arulselvan P, Wen CC, Lan CW, Chen YH, Wei WC, Yang NS (2012) Dietary administration of scallion extract effectively inhibits colorectal tumor growth: cellular and molecular mechanisms in mice. PLoS One 7:e44658CrossRefPubMedPubMedCentralGoogle Scholar
  6. Arulselvan P, Tan WS, Gothai S, Muniandy K, Fakurazi S, Esa NM, Alarfaj AA, Kumar SS (2016) Anti-inflammatory potential of ethyl acetate fraction of Moringa oleifera in down regulating the NF-kappaB signaling pathway in lipopolysaccharide-stimulated macrophages. Molecules 21:1452CrossRefGoogle Scholar
  7. Aziz MSA, Giribabu N, Rao PV, Salleh N (2017) Pancreatoprotective effects of Geniotrigona thoracica stingless bee honey in streptozotocin-nicotinamide-induced male diabetic rats. Biomed Pharmacother 89:135–145CrossRefPubMedGoogle Scholar
  8. Barkat MA, Abul H, Ahmad J, Khan MA, Beg S, Ahmad FJ (2018) Insights into the targeting potential of thymoquinone for therapeutic intervention against triple-negative breast cancer. Curr Drug Targets 19:70–80CrossRefPubMedGoogle Scholar
  9. Cai Y, Zhao B, Liang Q, Zhang Y, Cai J, Li G (2017) The selective effect of glycyrrhizin and glycyrrhetinic acid on topoisomerase II alpha and apoptosis in combination with etoposide on triple negative breast cancer MDA-MB-231 cells. Eur J Pharmacol 809:87–97CrossRefPubMedGoogle Scholar
  10. Cameron KS, Howard CB, Izevbigie EB, Hill BJ, Tchounwou PB (2013) Sensitivity and mechanisms of taxol-resistant prostate adenocarcinoma cells to Vernonia amygdalina extract. Exp Toxicol Pathol 65:759–765CrossRefPubMedGoogle Scholar
  11. Choi YK, Cho SG, Woo SM, Yun YJ, Park S, Shin YC, Ko SG (2014) Herbal extract SH003 suppresses tumor growth and metastasis of MDA-MB-231 breast cancer cells by inhibiting STAT3-IL-6 signaling. Mediat Inflam 2014:492173. CrossRefGoogle Scholar
  12. Ebrahim HY, Elsayed HE, Mohyeldin MM, Akl MR, Bhattacharjee J, Egbert S, El Sayed KA (2016) Norstictic acid inhibits breast cancer cell proliferation, migration, invasion, and in vivo invasive growth through targeting C-met. Phytother Res 30:557–566CrossRefPubMedPubMedCentralGoogle Scholar
  13. Foo JB, Yazan LS, Tor YS, Armania N, Ismail N, Imam MU, Yeap SK, Cheah YK, Abdullah R, Ismail M (2014) Induction of cell cycle arrest and apoptosis in caspase-3 deficient MCF-7 cells by Dillenia suffruticosa root extract via multiple signalling pathways. BMC Complement Altern Med 14:197CrossRefPubMedPubMedCentralGoogle Scholar
  14. Foo JB, Saiful Yazan LS, Tor YS, Wibowo A, Ismail N, Armania N, Cheah YK, Abdullah R (2016) Dillenia suffruticosa dichloromethane root extract induced apoptosis towards MDA-MB-231 triple-negative breast cancer cells. J Ethnopharmacol 187:195–204CrossRefPubMedGoogle Scholar
  15. Ganesan P, Arulselvan P, Choi DK (2017) Phytobioactive compound-based nanodelivery systems for the treatment of type 2 Diabetes mellitus-current status. Int J Nanomed 12:1097–1111CrossRefGoogle Scholar
  16. Giribabu N, Roslan J, Rekha SS, Salleh N (2016) Methanolic seed extract of Vitis vinifera ameliorates oxidative stress, inflammation and ATPase dysfunction in infarcted and non-infarcted heart of streptozotocin-nicotinamide induced male diabetic rats. Int J Cardiol 222:850–865CrossRefPubMedGoogle Scholar
  17. Giribabu N, Karim K, Kilari EK, Salleh N (2017) Phyllanthus niruri leaves aqueous extract improves kidney functions, ameliorates kidney oxidative stress, inflammation, fibrosis and apoptosis and enhances kidney cell proliferation in adult male rats with diabetes mellitus. J Ethnopharmacol 205:123–137CrossRefPubMedGoogle Scholar
  18. Gopinath K, Prakash D, Sudhandiran G (2011) Neuroprotective effect of naringin, a dietary flavonoid against 3-nitropropionic acid-induced neuronal apoptosis. Neurochem Int 59:1066–1073CrossRefPubMedGoogle Scholar
  19. Han S, Kim HM, Lee JM, Mok SY, Lee S (2010) Isolation and identification of polymethoxyflavones from the hybrid Citrus, hallabong. J Agric Food Chem 58:9488–9491CrossRefPubMedGoogle Scholar
  20. Hasanpourghadi M, Pandurangan AK, Karthikeyan C, Trivedi P, Mustafa MR (2017) Mechanisms of the anti-tumor activity of methyl 2-(−5-fluoro-2-hydroxyphenyl)-1 H-benzo[d]imidazole-5-carboxylate against breast cancer in vitro and in vivo. Oncotarget 8:28840–28853Google Scholar
  21. Hemmati AA, Olapour S, Varzi HN, Khodayar MJ, Dianat M, Mohammadian B, Yaghooti H (2017) Ellagic acid protects against arsenic trioxide-induced cardiotoxicity in rat. Hum Exp Toxicol (Online) 960327117701986.
  22. Herschkowitz JI, Simin K, Weigman VJ, Mikaelian I, Usary J, Hu Z, Rasmussen KE, Jones LP, Assefnia S, Chandrasekharan S, Backlund MG, Yin Y, Khramtsov AI, Bastein R, Quackenbush J, Glazer RI, Brown PH, Green JE, Kopelovich L, Furth PA, Palazzo JP, Olopade OI, Bernard PS, Churchill GA, Van Dyke T, Perou CM (2007) Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors. Genome Biol 8:R76CrossRefPubMedPubMedCentralGoogle Scholar
  23. Horie T, Tsukayama M, Yamada T, Miura I, Nakayama M (1986) Three flavone glycosides from Citrus sudachi. Phytochemistry 25:2621–2624CrossRefGoogle Scholar
  24. Howard C, Stevens J, Izevbigie E, Walker A, McDaniel O (2003) Time and dose-dependent modulation of phase 1 and phase 2 gene expression in response to treatment of MCF-7 cells with a natural anti-cancer agent. Cell Mol Biol 49:1057–1065PubMedGoogle Scholar
  25. Howard C, Cameron K, Gresham L, Zhang Y, Izevbigie E (2011) Environmental carcinogens and sensitization of paclitaxel and vincristine by Vernonia amygdalina extracts. Afr Environ Perspect 1:103–114Google Scholar
  26. Howard CB, McDowell R, Feleke K, Deer E, Stamps S, Thames E, Singh V, Pervin S (2016) Chemotherapeutic vulnerability of triple-negative breast cancer cell-derived tumors to pretreatment with Vernonia amygdalina aqueous extracts. Anticancer Res 36:3933–3943PubMedPubMedCentralGoogle Scholar
  27. Hsu RJ, Hsu YC, Chen SP, CL F, JC Y, Chang FW, Chen YH, Liu JM, Ho JY, CP Y (2015) The triterpenoids of Hibiscus syriacus induce apoptosis and inhibit cell migration in breast cancer cells. BMC Complement Altern Med 15:65. CrossRefPubMedPubMedCentralGoogle Scholar
  28. Huang YT, Wen CC, Chen YH, Huang WC, Huang LT, Lin WC, Arulselvan P, Liao JW, Lin SH, Hsiao PW, Kuo SC, Yang NS (2013) Dietary uptake of Wedelia chinensis extract attenuates dextran sulfate sodium-induced colitis in mice. PLoS One 8:e64152CrossRefPubMedPubMedCentralGoogle Scholar
  29. Ijeh II, Ejike CE (2011) Current perspectives on the medicinal potentials of Vernonia amygdalina del. J Med Plants Res 5:1051–1061Google Scholar
  30. Irvin WJ Jr, Carey LA (2008) What is triple-negative breast cancer. Eur J Cancer 44:2799–2805CrossRefPubMedGoogle Scholar
  31. Izevbigie EB (2003) Discovery of water-soluble anticancer agents (edotides) from a vegetable found in Benin City, Nigeria. Exp Biol Med 228:293–298CrossRefGoogle Scholar
  32. Izevbigie EB, Bryant JL, Walker A (2004) A novel natural inhibitor of extracellular signal-regulated kinases and human breast cancer cell growth. Exp Biol Med 229:163–169CrossRefGoogle Scholar
  33. Kalimutho M, Parsons K, Mittal D, Lopez JA, Srihari S, Khanna KK (2015) Targeted therapies for triple-negative breast cancer: combating a stubborn disease. Trends Pharmacol Sci 36:822–846CrossRefPubMedGoogle Scholar
  34. Kaplan HG, Malmgren JA, Atwood M (2009) T1N0 triple negative breast cancer: risk of recurrence and adjuvant chemotherapy. Breast J 15:454–460CrossRefPubMedGoogle Scholar
  35. Karthivashan G, Kura AU, Arulselvan Md Isa PN, Fakurazi S (2016) The modulatory effect of Moringa oleifera leaf extract on endogenous antioxidant systems and inflammatory markers in an acetaminophen-induced nephrotoxic mice model. Peer J 4:e2127CrossRefPubMedGoogle Scholar
  36. Katiyar SK, Pal HC, Prasad R (2017) Dietary proanthocyanidins prevent ultraviolet radiation-induced non-melanoma skin cancer through enhanced repair of damaged DNA-dependent activation of immune sensitivity. Semin Cancer Biol (Online) 46:138. CrossRefGoogle Scholar
  37. Khan RI, Bui MM (2010) A review of triple-negative breast cancer. Cancer Contr 17:173–176CrossRefGoogle Scholar
  38. Khan A, Chen H, Tania M, Zhang D (2011) Anticancer activities of Nigella sativa (black cumin). Afr J Trad Compl Altern Med 8:226–232Google Scholar
  39. Khokhar A (2012) Breast cancer in India: where do we stand and where do we go. Asian Pac J Cancer Prev 13:4861–4866CrossRefPubMedGoogle Scholar
  40. Kim SB, Kang OH, Joung DK, Mun SH, Seo YS, Cha MR, Ryu SY, Shin DW, Kwon DY (2013a) Anti-inflammatory effects of tectroside on UVB-induced HaCaT cells. Int J Mol Med 31:1471–1476CrossRefPubMedGoogle Scholar
  41. Kim DS, Ko JH, Jeon YD, Han YH, Kim HJ, Poudel A, Jung HJ, Ku SK, Kim SJ, Park SH (2013b) Ixeris dentata Nakai reduces clinical score and HIF-1 expression in experimental colitis in mice. Evid Based Complement Alternat Med 2013:671281. CrossRefPubMedPubMedCentralGoogle Scholar
  42. Kumari S, Badana AK, Mohan GM, Naik GS, Malla R (2017) Synergistic effects of coralyne and paclitaxel on cell migration and proliferation of breast cancer cells lines. Biomed Pharmacother 91:436–445CrossRefPubMedGoogle Scholar
  43. Kuriakose J, Lal Raisa H, Eldhose VAB, SLM (2017) Terminalia bellirica (Gaertn.) Roxb. fruit mitigates CCl4 induced oxidative stress and hepatotoxicity in rats. Biomed Pharmacother 93:327–333CrossRefPubMedGoogle Scholar
  44. Kwon MJ (2013) Emerging roles of claudins in human cancer. Int J Mol Sci 14:18148–18180CrossRefPubMedPubMedCentralGoogle Scholar
  45. Laraia L, Waldmann H (2017) Natural product inspired compound collections: evolutionary principle, chemical synthesis, phenotypic screening, and target identification. Drug Discov Today Technol 23:75–82CrossRefPubMedGoogle Scholar
  46. Lee HY, Lee GH, Kim HK, Kim SH, Park KP, Chae HJ, Kim HR (2013) Ixeris dentata induced regulation of amylase synthesis and secretion in glucose-treated human salivary gland cells. Food Chem Toxicol 62:739–749CrossRefPubMedGoogle Scholar
  47. Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA (2011) Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 121:2750–2767CrossRefPubMedPubMedCentralGoogle Scholar
  48. Li WW, Li BG, Chen YZ (1998) Flexuosol A, a new tetrastilbene from Vitis flexuosa. J Nat Prod 61:646–647CrossRefPubMedGoogle Scholar
  49. Li S, Pan MH, Lo CY, Tan D, Wang Y, Shahidi F, Ho CT (2009) Chemistry and health effects of polymethoxyflavones and hydroxylated polymethoxyflavones. J Funct Foods 1:2–12CrossRefGoogle Scholar
  50. Looi CY, Arya A, Cheah FK, Muharram B, Leong KH, Mohamad K, Wong WF, Rai N, Mustafa MR (2013) Induction of apoptosis in human breast cancer cells via caspase pathway by vernodalin isolated from Centratherum anthelminticum (L.) seeds. PLoS One 8:e56643CrossRefPubMedPubMedCentralGoogle Scholar
  51. Luan YY, Liu ZM, Zhong JY, Yao RY, HS Y (2015) Effect of grape seed proanthocyanidins on tumor vasculogenic mimicry in human triple-negative breast cancer cells. Asian Pac J Cancer Prev 16:531–535CrossRefPubMedGoogle Scholar
  52. Ma CX, Luo J, Ellis MJ (2010) Molecular profiling of triple negative breast cancer. Breast Dis 32:73–84CrossRefPubMedGoogle Scholar
  53. Mersin H, Yildirim E, Berberoglu U, Gulben K (2008) The prognostic importance of triple negative breast carcinoma. Breast 17:341–346CrossRefPubMedGoogle Scholar
  54. Montagna E, Maisonneuve P, Rotmensz N, Cancello G, Iorfida M, Balduzzi A, Galimberti V, Veronesi P, Luini A, Pruneri G (2013) Heterogeneity of triple-negative breast cancer: histologic subtyping to inform the outcome. Clin Breast Cancer 13:31–39CrossRefPubMedGoogle Scholar
  55. Muhammad AA, Arulselvan P, Cheah PS, Abas F, Fakurazi S (2016) Evaluation of wound healing properties of bioactive aqueous fraction from Moringa oleifera Lam on experimentally induced diabetic animal model. Drug Des Devel Ther 10:1715–1730CrossRefPubMedPubMedCentralGoogle Scholar
  56. Oh SH, Sung TH, Kim MR (2003) Ixeris dentata extract maintains glutathione concentrations in mouse brain tissue under oxidative stress induced by kainic acid. J Med Food 6:353–358CrossRefPubMedGoogle Scholar
  57. O’Reilly EA, Gubbins L, Sharma S, Tully R, Guang MH, Weiner-Gorzel K, McCaffrey J, Harrison M, Furlong F, Kell M, McCann A (2015) The fate of chemoresistance in triple negative breast cancer (TNBC). BBA Clin 3:257–275CrossRefPubMedPubMedCentralGoogle Scholar
  58. Oshima Y, Ueno Y (1993) Ampelopsins E,E,H and cis-ampelopsin E, oligostilbenes from Ampelopsis brevipedunculata var. Hancei roots. Phytochemistry 33:179–182CrossRefGoogle Scholar
  59. Padhye S, Banerjee S, Ahmad A, Mohammad R, Sarkar FH (2008) From here to eternity-the secret of pharaohs: therapeutic potential of black cumin seeds and beyond. Cancer Ther 6:495PubMedPubMedCentralGoogle Scholar
  60. Pan XB, Qu S, Jiang YM, Zhu XD (2015) Triple negative breast cancer versus non-triple negative breast cancer treated with breast conservation surgery followed by radiotherapy: a systematic review and meta-analysis. Breast Care 10:413–416CrossRefPubMedPubMedCentralGoogle Scholar
  61. Pandurangan AK, Ananda Sadagopan SK, Dharmalingam P, Ganapasam S (2014a) Luteolin, a bioflavonoid inhibits azoxymethane-induced colorectal cancer through activation of Nrf2 signaling. Toxicol Mech Methods 24:13–20CrossRefPubMedGoogle Scholar
  62. Pandurangan AK, Dharmalingam P, Sadagopan SK, Ganapasam S (2014b) Luteolin inhibits matrix metalloproteinase 9 and 2 in azoxymethane-induced colon carcinogenesis. Hum Exp Toxicol 33:1176–1185CrossRefPubMedGoogle Scholar
  63. Pandurangan AK, Kumar SA, Dharmalingam P, Ganapasam S (2014c) Luteolin, a bioflavonoid inhibits azoxymethane-induced colon carcinogenesis: involvement of iNOS and COX-2. Pharmacogn Mag 10:S306–S310CrossRefPubMedPubMedCentralGoogle Scholar
  64. Pandurangan AK, Mohebali N, Esa NM, Looi CY, Ismail S, Saadatdoust Z (2015a) Gallic acid suppresses inflammation in dextran sodium sulfate-induced colitis in mice: possible mechanisms. Int Immunopharmacol 28:1034–1043CrossRefPubMedGoogle Scholar
  65. Pandurangan AK, Mohebali N, Esa NM, Looi CY (2015b) Gallic acid attenuates dextran sulfate sodium-induced experimental colitis in BALB/c mice. Drug Des Devel Ther 9:3923–3934CrossRefPubMedPubMedCentralGoogle Scholar
  66. Pandurangan AK, Mohebali N, Hasanpourghadi M, Looi CY, Mustafa MR, Esa NM (2016) Boldine suppresses dextran sulfate sodium-induced mouse experimental colitis: NF-kappa B and IL-6/STAT3 as potential targets. Biofactors 42:247–258PubMedGoogle Scholar
  67. Park JY, Shin MS, Kim SN, Kim HY, Kim KH, Shin KS, Kang KS (2016) Polysaccharides from Korean citrus hallabong peels inhibit angiogenesis and breast cancer cell migration. Int J Biol Macromol 85:522–529CrossRefPubMedGoogle Scholar
  68. Perou CM (2010) Molecular stratification of triple-negative breast cancers. Oncologist 15:S39–S48CrossRefGoogle Scholar
  69. Prakash D, Sudhandiran G (2015) Dietary flavonoid fisetin regulates aluminium chloride-induced neuronal apoptosis in cortex and hippocampus of mice brain. J Nutr Biochem 26:1527–1539CrossRefPubMedGoogle Scholar
  70. Prat A, Parker JS, Karginova O, Fan C, Livasy C, Herschkowitz JI, He X, Perou CM (2010) Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res 12:R68CrossRefPubMedPubMedCentralGoogle Scholar
  71. Qi ZH, Meng J, Wang ZL, Sun HZ, Gong Y (2016) Antitumor effect of Ganoderma lipsiense extract on triple-negative breast cancer model mice and mechanism study. Zhongguo Zhong Xi Yi Jie He Za Zhi 36:366–369PubMedGoogle Scholar
  72. Rahman NA, Yazan LS, Wibowo A, Ahmat N, Foo JB, Tor YS, Yeap SK, Razali ZA, Ong YS, Fakurazi S (2016) Induction of apoptosis and G2/M arrest by ampelopsin E from dryobalanops towards triple negative breast cancer cells, MDA-MB-231. BMC Complement Altern Med 16:354. CrossRefPubMedPubMedCentralGoogle Scholar
  73. Rebhun JF, Glynn KM, Missler SR (2015) Identification of glabridin as a bioactive compound in licorice (Glycyrrhiza glabra L.) extract that activates human peroxisome proliferator-activated receptor gamma (PPARγ). Fitoterapia 106:55–61CrossRefPubMedGoogle Scholar
  74. Reis-Filho JS, Tutt AN (2008) Triple negative tumours: a critical review. Histopathol 52:108–118CrossRefGoogle Scholar
  75. Robles AJ, Du L, Cichewicz RH, Mooberry SL (2016) Maximiscin induces DNA damage, activates DNA damage response pathways, and has selective cytotoxic activity against a subtype of triple-negative breast cancer. J Nat Prod 79:1822–1827CrossRefPubMedPubMedCentralGoogle Scholar
  76. Saadatdoust Z, Pandurangan AK, Ananda Sadagopan SK, Esa NM, Ismail A, Mustafa MR (2015) Dietary cocoa inhibits colitis associated cancer: a crucial involvement of the IL-6/STAT3 pathway. J Nutr Biochem 26:1547–1558CrossRefPubMedGoogle Scholar
  77. Salih B, Sipahi T, Dönmez EO (2009) Ancient Nigella seeds from Boyali Höyük in north-central Turkey. J Ethnopharmacol 124:416–420CrossRefPubMedGoogle Scholar
  78. Sandhu GS, Erqou S, Patterson H, Mathew A (2016) Prevalence of triple-negative breast cancer in India: systematic review and meta-analysis. J Globe Oncol 2:412–421CrossRefGoogle Scholar
  79. Shamaladevi N, Lyn DA, Shaaban KA, Zhang L, Villate S, Rohr J, Lokeshwar BL (2013) Ericifolin: a novel antitumor compound from allspice that silences androgen receptor in prostate cancer. Carcinogenesis 34:1822–1832CrossRefPubMedPubMedCentralGoogle Scholar
  80. Shin SA, Lee HN, Choo GS, Kim HJ, Che JH, Jung JY (2017) Ixeris dentata (Thunb ex Thunb) Nakai extract inhibits proliferation and induces apoptosis in breast cancer cells through Akt/NF-kappaB pathways. Int J Mol Sci 18:275CrossRefPubMedCentralGoogle Scholar
  81. Siegel RL, Miller KD, Jemal A (2015) Cancer statistics 2015. CA Cancer J Clin 65:5–29CrossRefPubMedGoogle Scholar
  82. Siegel RL, Miller KD, Jemal A (2016) Cancer statistics 2016. CA Cancer J Clin 66:7–30CrossRefGoogle Scholar
  83. Stockmans G, Deraedt K, Wildiers H, Moerman P, Paridaens R (2008) Triple-negative breast cancer. Curr Opin Oncol 20:614–620CrossRefPubMedGoogle Scholar
  84. Taiko A (2000) Differences in the metabolism of glycyrrhizin, glycyrrhetic acid and glycyrrhetic acid monoglucuronide by human intestinal flora. Biol Pharm Bull 23:1418–1423CrossRefGoogle Scholar
  85. Tan AR, Swain SM (2008) Therapeutic strategies for triple-negative breast cancer. Cancer J 14:343–351CrossRefPubMedGoogle Scholar
  86. Tan BL, Norhaizan ME, Pandurangan AK, Hazilawati H, Roselina K (2016) Brewers rice attenuated aberrant crypt foci developing in colon of azoxymethane-treated rats. Pak J Pharm Sci 29:205–212PubMedGoogle Scholar
  87. Tatum JH, Berry RE (1979) Coumarins and psoralens in grapefruit peel oil. Phytochemistry 18:500–502CrossRefGoogle Scholar
  88. Tor YS, Yazan LS, Foo JB, Armania N, Cheah YK, Abdullah R, Imam MU, Ismail N, Ismail M (2014) Induction of apoptosis through oxidative stress-related pathways in MCF-7, human breast cancer cells, by ethyl acetate extract of Dillenia suffruticosa. BMC Complement Altern Med 14:55. CrossRefPubMedPubMedCentralGoogle Scholar
  89. Torki S, Soltani A, Shirzad H, Esmaeil N, Ghatrehsamani M (2017) Synergistic antitumor effect of NVP-BEZ235 and CAPE on MDA-MB-231 breast cancer cells. Biomed Pharmacother 92:39–45CrossRefPubMedGoogle Scholar
  90. Tzankova V, Aluani D, Kondeva-Burdina M, Yordanov Y, Odzhakov F, Apostolov A, Yoncheva K (2017) Hepatoprotective and antioxidant activity of quercetin loaded chitosan/alginate particles in vitro and in vivo in a model of paracetamol-induced toxicity. Biomed Pharmacother 92:569–579CrossRefPubMedGoogle Scholar
  91. White PA, Oliveira RC, Oliveira AP, Serafini MR, Araujo AA, Gelain DP, Moreira JC, Almeida JR, Quintans JS, Quintans-Junior LJ, Santos MR (2014) Antioxidant activity and mechanisms of action of natural compounds isolated from lichens: a systematic review. Molecules 19:14496–14527CrossRefPubMedGoogle Scholar
  92. Wibowo A, Ahmat N, Hamzah A, Latif F, Norrizah J, Khong H, Takayama H (2014) Identification and biological activity of secondary metabolites from Dryobalanops beccarii. Phytochem Lett 9:117–122CrossRefGoogle Scholar
  93. Woo SM, Kim AJ, Choi YK, Shin YC, Cho SG, Ko SG (2016) Synergistic effect of SH003 and doxorubicin in triple-negative breast cancer. Phytother Res 30:1817–1823CrossRefPubMedGoogle Scholar
  94. Wu CH, Chen AZ, Yen GC (2015) Protective effects of glycyrrhizic acid and 18β-glycyrrhetinic acid against cisplatin-induced nephrotoxicity in BALB/c mice. J Agric Food Chem 63:1200–1209CrossRefPubMedGoogle Scholar
  95. Yam C, Mani SA, Moulder SL (2017) Targeting the molecular subtypes of triple negative breast cancer: understanding the diversity to progress the field. Oncologist 22:1086. CrossRefPubMedPubMedCentralGoogle Scholar
  96. Yang X, Liu T, Chen B, Wang F, Yang Q, Chen X (2017) Grape seed proanthocyanidins prevent irradiation induced differentiation of human lung fibroblasts by ameliorating mitochondrial dysfunction. Sci Rep 7:62. CrossRefPubMedPubMedCentralGoogle Scholar
  97. Yao K, Shao J, Zhou K, Qiu H, Cao F, Li C, Dai D (2016) Grape seed proanthocyanidins induce apoptosis through the mitochondrial pathway in nasopharyngeal carcinoma CNE-2 cells. Oncol Rep 36:771–778CrossRefPubMedGoogle Scholar
  98. Yi JM, Hong SH, Lee HJ, Won JH, Kim JM, Jeong DM, Baek SH, Lim JP, Kim HM (2002) Ixeris dentata green sap inhibits both compound 48/80-induced aanaphylaxis like response and IgE-mediated anaphylactic response in murine model. Biol Pharma Bull 25:5–9CrossRefGoogle Scholar
  99. Yip CH, Taib NA, Mohamed I (2006) Epidemiology of breast cancer in Malaysia. Asian Pac J Cancer Prev 7:369–374PubMedGoogle Scholar
  100. Yip CH, Taib NA, Choo WY, Rampal S, Thong MK, Teo SH (2009) Clinical and pathologic differences between BRCA1, BRCA2, and non-BRCA associated breast cancers in a multiracial developing country. World J Surg 33:2077–2081CrossRefPubMedGoogle Scholar
  101. Yip CH, Bhoo PN, Teo S (2014) Review of breast cancer research in Malaysia. Med J Malaysia 69:8–12PubMedGoogle Scholar
  102. Yoon SW, Lee KP, Kim DY, Hwang DI, Won KJ, Lee DW, Lee HM (2017) Effect of absolute from Hibiscus syriacus L. flower on wound healing in keratinocytes. Pharmacogn Mag 13:85–89PubMedPubMedCentralGoogle Scholar
  103. Zhang L, Lokeshwar BL (2012) Medicinal properties of the Jamaican pepper plant Pimenta dioica and allspice. Curr Drug Targ 13:1900–1906CrossRefGoogle Scholar
  104. Zhang L, Shamaladevi N, Jayaprakasha GK, Patil BS, Lokeshwar BL (2015) Polyphenol-rich extract of Pimenta dioica berries (allspice) kills breast cancer cells by autophagy and delays growth of triple negative breast cancer in athymic mice. Oncotarget 6:16379–16395PubMedPubMedCentralGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.School of Life SciencesB. S. Abdur Rahman Crescent Institute of Science and TechnologyChennaiIndia
  2. 2.Faculty of Medicine, Centre for Natural Products and Drug Discovery (CENAR)University of MalayaKuala LumpurMalaysia

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