Enhanced anticancer effect of ABT-737 in combination with naringenin on gastric cancer cells

Zhang,Haiyang; Zhong,Xia; Zhang,Xiao; Shang,Deya; Zhou,Yi; Zhang,Chunqing

doi:10.3892/etm.2015.2912

Enhanced anticancer effect of ABT-737 in combination with naringenin on gastric cancer cells

Authors:
- Haiyang Zhang
- Xia Zhong
- Xiao Zhang
- Deya Shang
- Yi Zhou
- Chunqing Zhang
View Affiliations

Affiliations: Department of Emergency, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Shandong Center for Disease Control and Prevention, Jinan, Shandong 250014, P.R. China, Division of Hepatogastroenterology, Department of Internal Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
Published online on: December 4, 2015 https://doi.org/10.3892/etm.2015.2912
Pages: 669-673

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Gastric cancer is the second leading cause of cancer‑associated mortality and is a frequently occurring cancer worldwide. Multiple drug resistance of gastric cancer cells leads to the poor prognosis. In addition, overexpression of anti-apoptotic protein B-cell lymphoma (Bcl)-2 have been demonstrated in various cancer cells and is closely associated with drug resistance and poor prognosis. Naringenin is a flavonoid that has antimutagenic and anticarcinogenic activities in numerous cancer types. In the present study, naringenin and a Bcl‑2 inhibitor, ABT‑737, were used to investigate their combinative anticancer effect in the SGC7901 gastric cancer cell line. The results revealed that naringenin and ABT‑737 were able to inhibit SGC7901 cell growth and colony formation, alone or in combination. Furthermore, the combination of these drugs was found to further increase the cleavage of caspase‑3 and poly ADP‑ribose polymerase. Naringenin and ABT‑737 also decreased Akt activation and increased p53 expression, suggesting the involvement of these pathways in the inhibition of gastric cell growth.

View Figures

View References

1	Li Y, Yan PW, Huang XE and Li CG: MDR1 gene C3435T polymorphism is associated with clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy. Asian Pac J Cancer Prev. 12:2405–2409. 2011.PubMed/NCBI
2	Ferro A, Peleteiro B, Malvezzi M, Bosetti C, Bertuccio P, Levi F and Negri E: LaV ecchia C and Lunet N: Worldwide trends in gastric cancer mortality (1980-2011), with predictions to 2015, and incidence by subtype. Eur J Cancer. 50:1330–1344. 2014. View Article : Google Scholar : PubMed/NCBI
3	American Cancer Society Survival rates for stomach cancer by stage. https://www.cancer.org/cancer/stomach-cancer/detection-diagnosis-staging/survival-rates.htmlAccessed. June 24–2014
4	Shan YS, Hsu HP, Lai MD, Yen MC, Luo YP and Chen YL: Increased expression of argininosuccinate synthetase protein predicts poor prognosis in human gastric cancer. Oncology Rep. 33:49–57. 2015.
5	Yuan J, Li W, Tian Y and Wang X: Anti-proliferative effect of Flos Albiziae flavonoids on the human gastric cancer SGC-7901 cell line. Exp Ther Med. 5:51–56. 2013.PubMed/NCBI
6	Romagnolo DF and Selmin OI: Flavonoids and cancer prevention: A review of the evidence. J Nutr Gerontol Geriatr. 31:206–238. 2012. View Article : Google Scholar : PubMed/NCBI
7	Ekambaram G, Rajendran P, Magesh V and Sakthisekaran D: Naringenin reduces tumor size and weight lost in N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric carcinogenesis in rats. Nutr Res. 28:106–112. 2008. View Article : Google Scholar : PubMed/NCBI
8	Liao AC, Kuo CC, Huang YC, Yeh CW, Hseu YC, Liu JY and Hsu LS: Naringenin inhibits migration of bladder cancer cells through downregulation of AKT and MMP2. Mol Med Rep. 10:1531–1536. 2014.PubMed/NCBI
9	Hatkevich T, Ramos J, Santos-Sanchez I and Patel YM: A naringenin-tamoxifen combination impairs cell proliferation and survival of MCF-7 breast cancer cells. Exp Cell Res. 327:331–339. 2014. View Article : Google Scholar : PubMed/NCBI
10	Ahamad MS, Siddiqui S, Jafri A, Ahmad S, Afzal M and Arshad M: Induction of apoptosis and antiproliferative activity of naringenin in human epidermoid carcinoma cell through ROS generation and cell cycle arrest. PloS one. 9:e1100032014. View Article : Google Scholar : PubMed/NCBI
11	Arul D and Subramanian P: Naringenin (citrus flavonone) induces growth inhibition cell cycle arrest and apoptosis in human hepatocellular carcinoma cells. Pathol Oncol Res. 19:763–770. 2013. View Article : Google Scholar : PubMed/NCBI
12	Kang MH and Reynolds CP: Bcl-2 inhibitors: Targeting mitochondrial apoptotic pathways in cancer therapy. Clin Cancer Res. 15:1126–1132. 2009. View Article : Google Scholar : PubMed/NCBI
13	Tahir SK, Yang X, Anderson MG, Morgan-Lappe SE, Sarthy AV, Chen J, Warner RB, Ng SC, Fesik SW, Elmore SW, et al: Influence of Bcl-2 family members on the cellular response of small-cell lung cancer cell lines to ABT-737. Cancer Res. 67:1176–1183. 2007. View Article : Google Scholar : PubMed/NCBI
14	Konopleva M, Contractor R, Tsao T, Samudio I, Ruvolo PP, Kitada S, Deng X, Zhai D, Shi YX, Sneed T, et al: Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell. 10:375–388. 2006. View Article : Google Scholar : PubMed/NCBI
15	Bodet L, Gomez-Bougie P, Touzeau C, Dousset C, Descamps G, Maïga S, Avet-Loiseau H, Bataille R, Moreau P, Le Gouill S, et al: ABT-737 is highly effective against molecular subgroups of multiple myeloma. Blood. 118:3901–3910. 2011. View Article : Google Scholar : PubMed/NCBI
16	van Delft MF, Wei AH, Mason KD, Vandenberg CJ, Chen L, Czabotar PE, Willis SN, Scott CL, Day CL, Cory S, et al: The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized. Cancer cell. 10:389–399. 2006. View Article : Google Scholar : PubMed/NCBI
17	Sun XP, Zhang X, He C, Qiao H, Jiang X, Jiang H and Sun X: ABT-737 synergizes with arsenic trioxide to induce apoptosis of gastric carcinoma cells in vitro and in vivo. J Int Med Res. 40:1251–1264. 2012. View Article : Google Scholar : PubMed/NCBI
18	Li RF, Feng YQ, Chen JH, Ge LT, Xiao SY and Zuo XL: Naringenin suppresses K562 human leukemia cell proliferation and ameliorates Adriamycin-induced oxidative damage in polymorphonuclear leukocytes. Exp Ther Med. 9:697–706. 2015.PubMed/NCBI
19	Park JH, Jin CY, Lee BK, Kim GY, Choi YH and Jeong YK: Naringenin induces apoptosis through downregulation of Akt and caspase-3 activation in human leukemia THP-1 cells. Food Chem Toxicol. 46:3684–3690. 2008. View Article : Google Scholar : PubMed/NCBI
20	Parrondo R: deL as Pozas A, Reiner T and Perez-Stable C: ABT-737, a small molecule Bcl-2/Bcl-xL antagonist, increases antimitotic-mediated apoptosis in human prostate cancer cells. PeerJ. 1:e1442013. View Article : Google Scholar : PubMed/NCBI
21	Cristofanon S and Fulda S: ABT-737 promotes tBid mitochondrial accumulation to enhance TRAIL-induced apoptosis in glioblastoma cells. Cell Death Dis. 3:e4322012. View Article : Google Scholar : PubMed/NCBI
22	Yu DH, Ma CH, Yue ZQ, Yao X and Mao CM: Protective effect of naringenin against lipopolysaccharide-induced injury in normal human bronchial epithelium via suppression of MAPK signaling. Inflammation. 38:195–204. 2015. View Article : Google Scholar : PubMed/NCBI
23	Kapoor R, Rizvi F and Kakkar P: Naringenin prevents high glucose-induced mitochondria-mediated apoptosis involving AIF, Endo-G and caspases. Apoptosis. 18:9–27. 2013. View Article : Google Scholar : PubMed/NCBI
24	Kruiswijk F, Labuschagne CF and Vousden KH: p53 in survival, death and metabolic health, A lifeguard with a licence to kill. Nat Rev Mol Cell Biol. 16:393–405. 2015. View Article : Google Scholar : PubMed/NCBI
25	Warfel NA and Kraft AS: PIM kinase (and Akt) biology and signaling in tumors. Pharmacol Ther. 151:41–49. 2015. View Article : Google Scholar : PubMed/NCBI
26	Alam MA, Subhan N, Rahman MM, Uddin SJ, Reza HM and Sarker SD: Effect of citrus flavonoids, naringin and naringenin, on metabolic syndrome and their mechanisms of action. Adv Nutr. 5:404–417. 2014. View Article : Google Scholar : PubMed/NCBI
27	Sabarinathan D, Mahalakshmi P and Vanisree AJ: Naringenin promote apoptosis in cerebrally implanted C6 glioma cells. Mol Cell Biochem. 345:215–222. 2010. View Article : Google Scholar : PubMed/NCBI
28	Ekambaram G, Rajendran P, Devaraja R, Muthuvel R and Sakthisekaran D: Impact of naringenin on glycoprotein levels in N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric carcinogenesis in rats. Anticancer Drugs. 19:885–890. 2008. View Article : Google Scholar : PubMed/NCBI