Generic placeholder image

Recent Patents on Anti-Cancer Drug Discovery


ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

Research Article

Inhibitory Effect of Hydroxysafflor Yellow B on the Proliferation of Human Breast Cancer MCF-7 Cells

Author(s): Chuanjun Qu, Weiwei Zhu, Kaijie Dong, Zhaohai Pan, Ying Chen, Xiaoyu Chen, Xiaona Liu, Wenjuan Xu, Haiyan Lin, Qiusheng Zheng* and Defang Li*

Volume 14, Issue 2, 2019

Page: [187 - 197] Pages: 11

DOI: 10.2174/1574891X14666190516102218

Price: $65


Background: A recent patent has been issued for hydroxysafflor yellow A (HSYA) as a drug to prevent blood circulation disorders. Hydroxysafflor yellow B (HSYB), an isomer of HSYA with antioxidative effects, has been isolated from the florets of Carthamus tinctorius. The effects of HSYB on the proliferation of cancer cells and its mechanism of action have not been investigated.

Objective: The aims of this study were to investigate the anti-cancer effects and the molecular mechanism of HSYB for breast cancer MCF-7 cells.

Methods: MTT assays and colony formation assays were used to assess the survival and proliferation of MCF-7 cells, respectively. Hoechst 33258 and flow cytometry were used to measure cell apoptosis and flow cytometry to determine effects on the cell cycle. Western blots were used to measure protein levels.

Results: Treatment with HSYB reduced survival and proliferation of human breast cancer MCF-7 cells in a dose-dependent manner. Furthermore, HSYB arrested the MCF-7 cell cycle at the S phase and downregulated cyclin D1, cyclin E, and CDK2. Compared with a control group, HSYB suppressed the protein levels of p-PI3K, PI3K, AKT, and p-AKT in MCF-7 cells. In addition, HSYB decreased the levels of Bcl- 2, increased the levels of Bax, cleaved caspase-3 and caspase-9, and subsequently induced MCF-7 cell apoptosis.

Conclusion: These data demonstrate that HSYB arrests the MCF-7 cell cycle at the S phase and induces cell apoptosis. Patent US20170246228 indicates that HSYB can be potentially used for the prevention and treatment of human breast cancer.

Keywords: Breast cancer, cell apoptosis, cell cycle arrest, cell proliferation, hydroxysafflor yellow B, MCF-7 cells.

Yamaguchi M, Shizuoka JP. Method for suppressing proliferation and/or inducing apoptosis of cancer cells. US20170246228 (2017).
Buxant F, Kindt N, Laurent G, Noel JC, Saussez S. Antiproliferative effect of dexamethasone in the MCF-7 breast cancer cell line. Mol Med Rep 2015; 12(3): 4051-4.
Song QK, Wang XL, Zhou XN, Yang HB, Li YC, Wu JP, et al. Breast cancer challenges and screening in China: Lessons from Current registry data and population screening studies. Oncologist 2015; 20(7): 773-9.
Catherine AS, Dennis CS, Yi Z, Brock S, Mark GE. Predicting breast cancer recurrence. US20150203921 (2015).
Debeb BG, Gong Y, Atkinson RL, Sneige N, Huo L, Gonzalez-Angulo AM, et al. EZH2 expression correlates with locoregional recurrence after radiation in inflammatory breast cancer. J Exp Clin Cancer Res 2014; 33(1): 58-62.
Jo-Anne de la M, Lara C, Morgan CH, Buhle M, Jason NS, Karim CH, et al. Breast cancer: Current developments in molecular approaches to diagnosis and treatment. Recent Patents Anticancer Drug Discov 2014; 9(2): 153-75.
Brenda E, Karen SA. Immunotherapy for the treatment of breast cancer. Curr Oncol Rep 2015; 17(2): 5.
Raewyn CP, Andrew JC, Philippa AH. Cell proliferation is a key determinant of the outcome of FOXO3a activation. Biochem Biophys Res Commun 2015; 462(1): 78-84.
Shao JW, Chuan HW, Hai WX, Cong JZ, Zheng QY. Effect of optogenetic stimulus on the proliferation and cell cycle progression of neural stem cells. J Membr Biol 2014; 247(6): 493-500.
Khan Z, Khan AA, Yadav H, Prasad G, Bisen PS. Survivin, a molecular target for therapeutic interventions in squamous cell carcinoma. Cell Mol Biol Lett 2017; 22: 8-15.
Jun Q, Ni F, Jin NL, Wen JZ, Shi QX, Hong LL, et al. TRB3 is involved in free fatty acid-induced INS-1-derived cell apoptosis via the protein kinase C-δ pathway. PLoS One 2014; 9(5)e96089
Jiayi L, Qiang X, Ping L, Xue YZ, Yun XC. Mitochondrial estrogen receptor β inhibits cell apoptosis via interaction with bad in a ligand-independent manner. Mol Cell Biochem 2015; 401(1-2): 71-86.
Andrew AP, Jennifer R, Dawn C. Treatment of breast cancer. US20140296312 (2016).
Srivastava S, Athavale M, Shukre K, More G. Cancer stem cell targeting compounds. US20180169100 (2016).
Zhao X, Zhao J, Hu R, Yao Q, Zhang G, Shen H, et al. Ruanjian sanjie decoction exhibits antitumor activity by inducing cell apoptosis in breast cancer. Oncol Lett 2017; 13(5): 3071-9.
Zhou J, You W, Sun G, Li Y, Chen B, Ai J. The marine-derived oligosaccharide sulfate MS80, a novel transforming growth factor beta1 Inhibitor, reverses epithelial mesenchymal transition induced by transforming growth factor-beta1 and suppresses tumor metastasis. J Pharmacol Exp Ther 2016; 359(1): 54-61.
Cyril S, Florian M, Claudia C, Mario D, Marc D. Celecoxib prevents curcumin-induced apoptosis in a hematopoietic cancer cell model. Mol Carcinog 2015; 54(10): 999-1013.
Xu Y, Wang N, Shi ZX, Li YB, Zhou XQ, Sun ZW. In vitro mechanistic study of endosulfan-induced spermatogenic cell apoptosis in the mouse. Toxicol Ind Health 2016; 32(9): 1550-63.
Zhu PT, Mao M, Liu ZG, Tao L, Yan BC. Scutellarin suppresses human colorectal cancer metastasis and angiogenesis by targeting ephrinb2. Am J Transl Res 2017; 9(11): 5094-104.
Fanli K, Feng EL, Zhong MH, Yong J, Rruo YH, Xin S, et al. Anti-tumor and macrophage activation induced by alkali-extracted polysaccharide from Pleurotus ostreatus. Int J Biol Macromol 2014; 69: 561-6.
Lyu M, Yan CL, Liu HX, Wang TY, Shi XH, Liu JP, et al. Network pharmacology exploration reveals endothelial inflammation as a common mechanism for stroke and coronary artery disease treatment of Danhong injection. Sci Rep 2017; 7(1): 15427-34.
Zhou X, Siu WS, Fung CH, Cheng L, Wong CW, Zhang C, et al. Pro-angiogenic effects of Flos carthami whole extract in human microvascular endothelial cells in vitro and in zebrafish in vivo. Phytomedicine 2014; 21(11): 1256-63.
Feng Y, Ben C, Min L, Yongling C. Hydroxysafflor yellow A sodium and preparation as well as application thereof. US9243019 (2016).
Wang YQ, Tang X, Li JF, Wu YL, Sun YY, Fang MJ, et al. Development of an on-line mixed-mode gel liquid chromatography / reversed phase liquid chromatography method for separation of water extract from Flos carthami. J Chromatogr A 2017; 1519: 145-51.
Zhong BL, Hong XZ, Yong QY, Lian BL, Shao JL, Jun YZ, et al. Safflower polysaccharide inhibits the proliferation and metastasis of MCF-7 breast cancer cell. Mol Med Rep 2015; 11(6): 4611-6.
Yue S, Tang Y, Xu C, Li S, Zhu Y, Duan JA. Two new quinochalcone C-glycosides from the florets of Carthamus tinctorius. Int J Mol Sci 2014; 15(9): 16760-71.
Yue SJ, Tang YP, Wang LY, Tang H, Li SJ. Liu, P Su, et al. Separation and evaluation of antioxidant constituents from Carthamus tinctorius. Zhongguo Zhongyao Zazhi 2014; 39(17): 3295-300. [in Chinese].
Shan MX, Min XC, Wen BC, Jun GH, Jian SJ, Shu PH, et al. Chemopreventive effect of chalcone derivative, L2H17, in colon cancer development. BMC Cancer 2015; 15: 870.
Fang FY, Jing ML, Jin HZ, Dong W, Shao SC, Xian YB. Hydroxysafflor yellow A inhibits angiogenesis of hepatocellular carcinoma via blocking ERK/MAPK and NF-κB signaling pathway in H22 tumor-bearing mice. Eur J Pharmacol 2015; 754: 105-14.
Cao YY, Yu J, Liu TT, Yang KX, Yang LY, Chen Q, et al. Plumbagin inhibits the proliferation and survival of esophageal cancer cells by blocking STAT3-PLK1-AKT signaling. Cell Death Dis 2018; 9(2): 17-25.
Yan Z, Feng J, Peng J, Lai Z, Zhang L, Jin Y, et al. Chloroform extract of Hedyotis diffusa Willd inhibits viability of human colorectal cancer cells via suppression of AKT and ERK signaling pathways. Oncol Lett 2017; 14(6): 7923-30.
Sze-Ue IL, Hui X, Hong WC, Dong L, Peter WG, Ladan F, et al. The BIRC6 gene as a novel target for therapy of prostate cancer: Dual targeting of inhibitors of apoptosis. Oncotarget 2014; 5(16): 6896-908.
Wen SW, Li HS, Wei DX, Hua Y. Essential role of angiotensin receptors in the modulation of intestinal epithelial cell apoptosis. J Pediatr Gastroenterol Nutr 2013; 57(5): 562-9.
Chun HC, Zhao J, Jun HY, Lei Y, Ke W, Ying YC, et al. The involvement of programmed cell death 5 (PDCD5) in the regulation of apoptosis in cerebral ischemia/reperfusion injury. CNS Neurosci Ther 2013; 19(8): 566-76.
Mark GE, Xiao JM, Dennis CS. Grading of breast cancer. US20090092973 (2009).
Liu M, Yin H, Qian X, Dong J, Qian Z, Miao J. Xanthohumol, a prenylated chalcone from hops, inhibits the viability and stemness of doxorubicin-resistant MCF-7/ADR cells. Molecules 2016; 22(1): 45-53.
Shrivastava S, Jeengar MK, Thummuri D, Koval A, Katanaev VL, Marepally S, et al. Cardamonin, a chalcone, inhibits human triple negative breast cancer cell invasiveness by downregulation of Wnt/beta-catenin signaling cascades and reversal of epithelial-mesenchymal transition. Biofactors 2017; 43(2): 152-69.
Kang TH, Seo JH, Oh H, Yoon G, Chae JI, Shim JH. Licochalcone A suppresses specificity protein 1 as a novel target in human breast cancer cells. J Cell Biochem 2017; 118(12): 4652-63.
Yu L, Ma J, Han J, Wang B, Chen X, Gao C, et al. Licochalcone B arrests cell cycle progression and induces apoptosis in human breast cancer MCF-7 cells. Recent Patents Anticancer Drug Discov 2016; 11(4): 444-52.
Zilla MK, Nayak D, Amin H, Nalli Y, Rah B, Chakraborty S, et al. 4′-Demethyl-deoxypodophyllotoxin glucoside isolated from Podophyllum hexandrum exhibits potential anticancer activities by altering Chk-2 signaling pathway in MCF-7 breast cancer cells. Chem Biol Interact 2014; 224: 100-7.
Ahmed H, Moawad A, Owis A, AbouZid S, Ahmed O. Flavonoids of Calligonum polygonoides and their cytotoxicity. Pharm Biol 2016; 54(10): 2119-26.
Devi PS, Kumar MS, Das SM. Evaluation of antiproliferative activity of red sorghum bran anthocyanin on a human breast cancer cell line (MCF-7). Int J Breast Cancer 2011; 891481-9.
Keswani T, Mitra S, Bhattacharyya A. Copper-induced immunotoxicity involves cell cycle arrest and cell death in the liver. Environ Toxicol 2015; 30(4): 411-21.
Wang X, Sun YY, Zhao C, Qu FZ, Zhao YQ. 12-Chloracetyl-PPD, a novel dammarane derivative, shows anti-cancer activity via delay the progression of cell cycle G2/M phase and reactive oxygen species-mediate cell apoptosis. Eur J Pharmacol 2017; 798: 49-56.
Tsai TC, Huang HP, Chang KT, Wang CJ, Chang YC. Anthocyanins from roselle extract arrest cell cycle G2/M phase transition via ATM/Chk pathway in p53-deficient leukemia HL-60 cells. Environ Toxicol 2017; 32(4): 1290-304.
Li H, Peng X, Wang Y, Gao S, Xiong L, Fan J, et al. Atg5-mediated autophagy deficiency in proximal tubules promotes cell cycle G2/M arrest and renal fibrosis. Autophagy 2016; 12(9): 1472-86.
Hilakivi-Clarke L, Wang C, Kalil M, Riggins R, Pestell RG. Nutritional modulation of the cell cycle and breast cancer. Endocr Relat Cancer 2004; 11(4): 603-22.
Li T, Zhao X, Mo Z, Huang W, Yan H, Ling Z, et al. Formononetin promotes cell cycle arrest via downregulation of Akt/Cyclin D1/CDK4 in human prostate cancer cells. Cell Physiol Biochem 2014; 34(4): 1351-8.
Sebti SM, Lawrence NJ, Turkson J. Platinum compounds that inhibit constitutive STAT3 signaling and induce cell cycle AR malignant cells. US20180256564 (2018).
Wang B, Zhou X, Wang Y, Li R. Trifluoperazine inhibits mesangial cell proliferation by arresting cell cycle-dependent mechanisms. Med Sci Monit 2017; 23: 3461-9.
Wang HY, Xiong GF, Zhang JX, Xu H, Guo WH, Xu JJ, et al. The role of XPD in cell apoptosis and viability and its relationship with p53 and CDK2 in hepatoma cells. Med Oncol 2012; 29(1): 161-7.
Huang SY, Hsieh MJ, Chen CY, Chen YJ, Chen JY, Chen MR, et al. Epstein-Barr virus Rta-mediated transactivation of p21 and 14-3-3σ arrests cells at the G1/S transition by reducing cyclin E/CDK2 activity. J Gen Virol 2012; 93(Pt 1): 139-49.
Kim SA, Ryu HW, Lee KS, Cho JW. Application of platelet-rich plasma accelerates the wound healing process in acute and chronic ulcers through rapid migration and upregulation of cyclin A and CDK4 in HaCaT cells. Mol Med Rep 2013; 7(2): 476-80.
Yang H, Zhao X, Zhao L, Liu L, Li J, Jia W, et al. PRMT5 competitively binds to CDK4 to promote G1-S transition upon glucose induction in hepatocellular carcinoma. Oncotarget 2016; 7(44): 72131-47.
Park MA, Hwang KA, Lee HR, Yi BR, Jeung EB, Choi KC. Cell growth of BG-1 ovarian cancer cells is promoted by di-n-butyl phthalate and hexabromocyclododecane via upregulation of the cyclin D and cyclin-dependent kinase-4 genes. Mol Med Rep 2012; 5(3): 761-6.
Corin I, Larsson L, Bergstrom J, Gustavsson B, Derwinger K. A study of the expression of Cyclin E and its isoforms in tumor and adjacent mucosa, correlated to patient outcome in early colon cancer. Acta Oncol 2010; 49(1): 63-9.
Mitchell D, Rodgers K, Hanly J, McMahon B, Brady HR, Martin F, et al. Lipoxins inhibit Akt / PKB activation and cell cycle progression in human mesangial cells. Am J Pathol 2004; 164(3): 937-46.
Liu Y, Qi Y, Bai ZH, Ni CX, Ren QH, Xu WH, et al. A novel matrine derivate inhibits differentiated human hepatoma cells and hepatic cancer stem-like cells by suppressing PI3K/AKT signaling pathways. Acta Pharmacol Sin 2017; 38(1): 120-32.
Munugalavadla V, Mariathasan S, Slaga D, Du C, Berry L, Del Rosario G, et al. The PI3K inhibitor GDC-0941 combines with existing clinical regimens for superior activity in multiple myeloma. Oncogene 2014; 33(3): 316-25.
Liao CL, Lin JH, Lien JC, Hsu SC, Chueh FS, Yu CC, et al. The crude extract of Corni fructus inhibits the migration and invasion of U-2OS human osteosarcoma cells through the inhibition of matrix metalloproteinase-2/-9 by MAPK signaling. Environ Toxicol 2015; 30(1): 53-63.
Guo D, Ye J, Dai J, Li L, Chen F, Ma D, et al. Notch-1 regulates Akt signaling pathway and the expression of cell cycle regulatory proteins cyclin D1, CDK2 and p21 in T-ALL cell lines. Leuk Res 2016; 33(4): 678-85.
Parekh P, Motiwale L, Naik N, Rao KV. Downregulation of cyclin D1 is associated with decreased levels of p38 MAP kinases, Akt/PKB and Pak1 during chemopreventive effects of resveratrol in liver cancer cells. Exp Toxicol Pathol 2011; 63(1-2): 167-73.
Guzzo MF, Carvalho LR, Bronstein MD. Apoptosis: Its role in pituitary development and neoplastic pituitary tissue. Pituitary 2014; 17(2): 157-62.
Scatena R. Mitochondria and cancer: A growing role in apoptosis, cancer cell metabolism and dedifferentiation. Adv Exp Med Biol 2012; 942: 287-308.
You MK, Kim HJ, Kook JH, Kim HASt. John’s Wort regulates proliferation and apoptosis in MCF-7 human breast cancer cells by inhibiting AMPK/mTOR and activating the mitochondrial pathway. Int J Mol Sci 2018; 19(4): 87-95.
Sun Y, Lin Y, Li H, Liu J, Sheng X, Zhang W. 2,5-Hexanedione induces human ovarian granulosa cell apoptosis through BCL-2, BAX, and CASPASE-3 signaling pathways. Arch Toxicol 2012; 86(2): 205-15.
Wang P, Xu J, Zhang C. CREB, a possible upstream regulator of Bcl-2 in trichosanthin-induced HeLa cell apoptosis. Mol Biol Rep 2010; 37(4): 1891-6.
Jin S, Zhang QY, Kang XM, Wang JX, Zhao WH. Daidzein induces MCF-7 breast cancer cell apoptosis via the mitochondrial pathway. Ann Oncol 2010; 21(2): 263-8.
Azimian H, Bahreyni-Toossi MT, Rezaei AR, Rafatpanah H, Hamzehloei T, Fardid R. Up-regulation of Bcl-2 expression in cultured human lymphocytes after exposure to low doses of gamma radiation. J Med Phys 2015; 40(1): 38-44.
Hasenjager A, Gillissen B, Muller A, Normand G, Hemmati PG, Schuler M, et al. Smac induces cytochrome c release and apoptosis independently from Bax / Bcl-x(L) in a strictly caspase-3-dependent manner in human carcinoma cells. Oncogene 2004; 23(26): 4523-35.
Yu FS, Yu CS, Chen JC, Yang JL, Lu HF, Chang SJ, et al. Tetrandrine induces apoptosis Via caspase-8, -9, and -3 and poly (ADP ribose) polymerase dependent pathways and autophagy through beclin-1/ LC3-I, II signaling pathways in human oral cancer HSC-3 cells. Environ Toxicol 2016; 31(4): 395-406.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy