Anticancer effects of liriodenine on the cell growth and apoptosis of human breast cancer MCF-7 cells through the upregulation of p53 expression

Li,Zhi‑Hua; Gao,Jin; Hu,Ping‑Hua; Xiong,Jian‑Ping

doi:10.3892/ol.2017.6418

Anticancer effects of liriodenine on the cell growth and apoptosis of human breast cancer MCF-7 cells through the upregulation of p53 expression

Authors:
- Zhi‑Hua Li
- Jin Gao
- Ping‑Hua Hu
- Jian‑Ping Xiong
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Affiliations: Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330009, P.R. China, Department of Breast Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, P.R. China, Prevention and Cure Center of Breast Disease, Third Hospital of Nanchang, Nanchang, Jiangxi 330009, P.R. China
Published online on: June 19, 2017 https://doi.org/10.3892/ol.2017.6418
Pages: 1979-1984
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Liriodenine has wide pharmacological functions in phytochemistry, pharmacology and antitumor activities. The anticancer effects of liriodenine on the cell growth and apoptosis of human breast cancer MCF‑7 cells, and the underlying mechanisms, are yet to be elucidated. Therefore, the present study investigated the anticancer effects of liriodenine on the cell growth and apoptosis of human breast cancer MCF‑7 cells. We used MTT assay to measure cell growth, and flow cytometer and DAPI staining was used to analyze cell apoptosis. Then, Western blot analysis was executed to measure B‑cell lymphoma‑2 protein (Bcl‑2), cyclin D1, vascular endothelial growth factor (VEGF), and p53 protein expression. The effect of liriodenine induced significant apoptosis and suppression of cell growth of the MCF‑7 cells. Furthermore, the potential mechanism underlying its antitumor effect on MCF‑7 cells may result from activation of caspase‑3 activity, Bcl‑2, cyclin D1 and VEGF, and promotion of p53 protein expression in MCF‑7 cells. Therefore, the present results indicated that the anticancer effects of liriodenine suppress cell growth and induce the apoptosis of human breast cancer MCF‑7 cells through inhibition of Bcl‑2, cyclin D1 and VEGF expression, and upregulation of p53 expression. Therefore, liriodenine may be a potential therapy for the treatment of human breast cancer.

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1	Metzger-Filho O, de Azambuja E, Bradbury I, Saini KS, Bines J, Simon SD, Dooren VV, Aktan G, Pritchard KI, Wolff AC, et al: Analysis of regional timelines to set up a global phase III clinical trial in breast cancer: The adjuvant lapatinib and/or trastuzumab treatment optimization experience. Oncologist. 18:134–140. 2013. View Article : Google Scholar : PubMed/NCBI
2	Bower JE, Greendale G, Crosswell AD, Garet D, Sternlieb B, Ganz PA, Irwin MR, Olmstead R, Arevalo J and Cole SW: Yoga reduces inflammatory signaling in fatigued breast cancer survivors: A randomized controlled trial. Psychoneuroendocrinology. 43:20–29. 2014. View Article : Google Scholar : PubMed/NCBI
3	Buckley A, McQuaid S, Johnson P and Buggy DJ: Effect of anaesthetic technique on the natural killer cell anti-tumour activity of serum from women undergoing breast cancer surgery: A pilot study. Br J Anaesth. 113 Suppl 1:i56–i62. 2014. View Article : Google Scholar : PubMed/NCBI
4	Ansari M, Porouhan P, Mohammadianpanah M, Omidvari S, Mosalaei A, Ahmadloo N, Nasrollahi H and Hamedi SH: Efficacy of ginger in control of chemotherapy induced nausea and vomiting in breast cancer patients receiving doxorubicin-based chemotherapy. Asian Pac J Cancer Prev. 17:3877–3880. 2016.PubMed/NCBI
5	Mrózek E, Layman R, Ramaswamy B, Lustberg M, Vecchione A, Knopp MV and Shapiro CL: Phase II trial of neoadjuvant weekly nanoparticle albumin-bound paclitaxel, carboplatin, and biweekly bevacizumab therapy in women with clinical stage II or III HER2-negative breast cancer. Clin Breast Cancer. 14:228–234. 2014. View Article : Google Scholar : PubMed/NCBI
6	Pu Z, Zhang X, Chen Q, Yuan X and Xie H: Establishment of an expression platform of OATP1B1 388GG and 521CC genetic polymorphism and the therapeutic effect of tamoxifen in MCF-7 cells. Oncol Rep. 33:2420–2428. 2015.PubMed/NCBI
7	Hu D, Su C, Jiang M, Shen Y, Shi A, Zhao F, Chen R, Shen Z, Bao J and Tang W: Fenofibrate inhibited pancreatic cancer cells proliferation via activation of p53 mediated by upregulation of LncRNA MEG3. Biochem Biophys Res Commun. 471:290–295. 2016. View Article : Google Scholar : PubMed/NCBI
8	Shokouh TZ, Ezatollah A and Barand P: Interrelationships Between Ki67, HER2/neu, p53, ER, and PR status and their associations with tumor grade and lymph node involvement in breast carcinoma subtypes: Retrospective-observational analytical study. Medicine (Baltimore). 94:e13592015. View Article : Google Scholar : PubMed/NCBI
9	Antony ML, Kim SH and Singh SV: Critical role of p53 upregulated modulator of apoptosis in benzyl isothiocyanate-induced apoptotic cell death. PLoS One. 7:e322672012. View Article : Google Scholar : PubMed/NCBI
10	Wong FC, Woo CC, Hsu A and Tan BK: The anti-cancer activities of Vernonia amygdalina extract in human breast cancer cell lines are mediated through caspase-dependent and p53-independent pathways. PLoS One. 8:e780212013. View Article : Google Scholar : PubMed/NCBI
11	Ali A, Shah AS and Ahmad A: Gain-of-function of mutant p53: Mutant p53 enhances cancer progression by inhibiting KLF17 expression in invasive breast carcinoma cells. Cancer Lett. 354:87–96. 2014. View Article : Google Scholar : PubMed/NCBI
12	Hsieh TJ, Liu TZ, Chern CL, Tsao DA, Lu FJ, Syu YH, Hsieh PY, Hu HS, Chang TT and Chen CH: Liriodenine inhibits the proliferation of human hepatoma cell lines by blocking cell cycle progression and nitric oxide-mediated activation of p53 expression. Food Chem Toxicol. 43:1117–1126. 2005. View Article : Google Scholar : PubMed/NCBI
13	Nordin N, Majid NA, Hashim NM, Rahman MA, Hassan Z and Ali HM: Liriodenine, an aporphine alkaloid from Enicosanthellum pulchrum, inhibits proliferation of human ovarian cancer cells through induction of apoptosis via the mitochondrial signaling pathway and blocking cell cycle progression. Drug Des Devel Ther. 9:1437–1448. 2015.PubMed/NCBI
14	Hufford CD, Sharma AS and Oguntimein BO: Antibacterial and antifungal activity of liriodenine and related oxoaporphine alkaloids. J Pharm Sci. 69:1180–1183. 1980. View Article : Google Scholar : PubMed/NCBI
15	De la Cruz-Chacón I, González-Esquinca AR, Fefer P Guevara and Garcia LF Jimenez: Liriodenine, early antimicrobial defence in Annona diversifolia. Z Naturforsch C. 66:377–384. 2011. View Article : Google Scholar : PubMed/NCBI
16	Li L, Xu Y and Wang B: Liriodenine induces the apoptosis of human laryngocarcinoma cells via the upregulation of p53 expression. Oncol Lett. 9:1121–1127. 2015.PubMed/NCBI
17	Zuo S, Liu C, Wang J, Wang F, Xu W, Cui S, Yuan L, Chen X, Fan W, Cui M and Song G: IGFBP-rP1 induces p21 expression through a p53-independent pathway, leading to cellular senescence of MCF-7 breast cancer cells. J Cancer Res Clin Oncol. 138:1045–1055. 2012. View Article : Google Scholar : PubMed/NCBI
18	Verma S and Rao BJ: p53 suppresses BRCA2-stimulated ATPase and strand exchange functions of human RAD51. J Biochem. 154:237–248. 2013. View Article : Google Scholar : PubMed/NCBI
19	Chang HC, Chang FR, Wu YC and Lai YH: Anti-cancer effect of liriodenine on human lung cancer cells. Kaohsiung J Med Sci. 20:365–371. 2004. View Article : Google Scholar : PubMed/NCBI
20	Saxena NK, Vertino PM, Anania FA and Sharma D: Leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 promoter via activation of Stat3. J Biol Chem. 282:13316–13325. 2007. View Article : Google Scholar : PubMed/NCBI
21	Feldt M, Bjarnadottir O, Kimbung S, Jirström K, Bendahl PO, Veerla S, Grabau D, Hedenfalk I and Borgquist S: Statin-induced anti-proliferative effects via cyclin D1 and p27 in a window-of-opportunity breast cancer trial. J Transl Med. 13:1332015. View Article : Google Scholar : PubMed/NCBI
22	Mohammadizadeh F, Hani M, Ranaee M and Bagheri M: Role of cyclin D1 in breast carcinoma. J Res Med Sci. 18:1021–1025. 2013.PubMed/NCBI
23	Gonzalez-Sarrias A, Ma H, Edmonds ME and Seeram NP: Maple polyphenols, ginnalins A-C, induce S- and G2/M-cell cycle arrest in colon and breast cancer cells mediated by decreasing cyclins A and D1 levels. Food Chem. 136:636–642. 2013. View Article : Google Scholar : PubMed/NCBI
24	Coates AS, Millar EK, O'Toole SA, Molloy TJ, Viale G, Goldhirsch A, Regan MM, Gelber RD, Sun Z, Castiglione-Gertsch M, et al: Prognostic interaction between expression of p53 and estrogen receptor in patients with node-negative breast cancer: Results from IBCSG Trials VIII and IX. Breast Cancer Res. 14:R1432012. View Article : Google Scholar : PubMed/NCBI
25	Zhang Z, Wang CZ, Du GJ, Qi LW, Calway T, He TC, Du W and Yuan CS: Genistein induces G2/M cell cycle arrest and apoptosis via ATM/p53-dependent pathway in human colon cancer cells. Int J Oncol. 43:289–296. 2013.PubMed/NCBI
26	Liu S and Qian W: Need for clarification of data in a recent meta-analysis on vascular endothelial growth factor (VEGF) and risk of breast cancer. Cytokine. 60:5962012. View Article : Google Scholar : PubMed/NCBI
27	Groves MD, Hess KR, Puduvalli VK, Colman H, Conrad CA, Gilbert MR, Weinberg J, Cristofanilli M, Yung WK and Liu TJ: Biomarkers of disease: Cerebrospinal fluid vascular endothelial growth factor (VEGF) and stromal cell derived factor (SDF)-1 levels in patients with neoplastic meningitis (NM) due to breast cancer, lung cancer and melanoma. J Neurooncol. 94:229–234. 2009. View Article : Google Scholar : PubMed/NCBI