Survivin suppression through STAT3/β-catenin is essential for resveratrol-induced melanoma apoptosis

Habibie,Habibie; Yokoyama,Satoru; Abdelhamed,Sherif; Awale,Suresh; Sakurai,Hiroaki; Hayakawa,Yoshihiro; Saiki,Ikuo

doi:10.3892/ijo.2014.2480

Survivin suppression through STAT3/β-catenin is essential for resveratrol-induced melanoma apoptosis

Authors:
- Habibie Habibie
- Satoru Yokoyama
- Sherif Abdelhamed
- Suresh Awale
- Hiroaki Sakurai
- Yoshihiro Hayakawa
- Ikuo Saiki
View Affiliations

Affiliations: Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan, Frontier Research Core for Life Sciences, University of Toyama, Toyama 930-0194, Japan
Published online on: June 3, 2014 https://doi.org/10.3892/ijo.2014.2480
Pages: 895-901

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

Although many chemotherapies have been developed for melanomas, successful therapy would be aided by the identification of intrinsic mechanisms that are crucial for melanoma survival. Here, we used resveratrol, a phytoalexin, as an anti-melanoma reagent. Applying resveratrol to various human and murine melanoma cell lines, we show that survivin is essential for melanoma survival in vitro and in vivo and is targeted by resveratrol. Furthermore, we identify the downregulation of survivin transcription by resveratrol through the suppression of β-catenin and STAT3. In addition, overexpression of survivin protects melanoma cells from resveratrol-induced apoptosis. Collectively, these studies establish that targeting survivin could provide an opportunity to treat melanoma patients.

View Figures

View References

1	Chudnovsky Y, Khavari PA and Adams AE: Melanoma genetics and the development of rational therapeutics. J Clin Invest. 115:813–824. 2005. View Article : Google Scholar : PubMed/NCBI
2	Jemal A, Devesa SS, Fears TR and Hartge P: Cancer surveillance series: changing patterns of cutaneous malignant melanoma mortality rates among whites in the United States. J Natl Cancer Inst. 92:811–818. 2000. View Article : Google Scholar
3	Jemal A, Devesa SS, Hartge P and Tucker MA: Recent trends in cutaneous melanoma incidence among whites in the United States. J Natl Cancer Inst. 93:678–683. 2001. View Article : Google Scholar : PubMed/NCBI
4	Jemal A, Siegel R, Ward E, Hao Y, Xu J and Thun MJ: Cancer statistics, 2009. CA Cancer J Clin. 59:225–249. 2009. View Article : Google Scholar
5	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar
6	Flaherty KT, Puzanov I, Kim KB, et al: Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 363:809–819. 2010. View Article : Google Scholar : PubMed/NCBI
7	Nashan D, Muller ML, Grabbe S, Wustlich S and Enk A: Systemic therapy of disseminated malignant melanoma: an evidence-based overview of the state-of-the-art in daily routine. J Eur Acad Dermatol Venereol. 21:1305–1318. 2007. View Article : Google Scholar : PubMed/NCBI
8	Petrovski G, Gurusamy N and Das DK: Resveratrol in cardiovascular health and disease. Ann NY Acad Sci. 1215:22–33. 2011. View Article : Google Scholar : PubMed/NCBI
9	Szkudelska K and Szkudelski T: Resveratrol, obesity and diabetes. Eur J Pharmacol. 635:1–8. 2010. View Article : Google Scholar : PubMed/NCBI
10	Signorelli P and Ghidoni R: Resveratrol as an anticancer nutrient: molecular basis, open questions and promises. J Nutr Biochem. 16:449–466. 2005. View Article : Google Scholar : PubMed/NCBI
11	Aggarwal BB, Bhardwaj A, Aggarwal RS, Seeram NP, Shishodia S and Takada Y: Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Anticancer Res. 24:2783–2840. 2004.PubMed/NCBI
12	Niles RM, McFarland M, Weimer MB, Redkar A, Fu YM and Meadows GG: Resveratrol is a potent inducer of apoptosis in human melanoma cells. Cancer Lett. 190:157–163. 2003. View Article : Google Scholar : PubMed/NCBI
13	Fulda S and Debatin KM: Sensitization for anticancer drug-induced apoptosis by the chemopreventive agent resveratrol. Oncogene. 23:6702–6711. 2004. View Article : Google Scholar : PubMed/NCBI
14	Ivanov VN, Partridge MA, Johnson GE, Huang SX, Zhou H and Hei TK: Resveratrol sensitizes melanomas to TRAIL through modulation of antiapoptotic gene expression. Exp Cell Res. 314:1163–1176. 2008. View Article : Google Scholar : PubMed/NCBI
15	Fulda S and Debatin KM: Sensitization for tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by the chemopreventive agent resveratrol. Cancer Res. 64:337–346. 2004. View Article : Google Scholar : PubMed/NCBI
16	Fang Y, Bradley MJ, Cook KM, Herrick EJ and Nicholl MB: A potential role for resveratrol as a radiation sensitizer for melanoma treatment. J Surg Res. 183:645–653. 2013. View Article : Google Scholar : PubMed/NCBI
17	Kim MY: Nitric oxide triggers apoptosis in A375 human melanoma cells treated with capsaicin and resveratrol. Mol Med Rep. 5:585–591. 2012.PubMed/NCBI
18	Osmond GW, Augustine CK, Zipfel PA, Padussis J and Tyler DS: Enhancing melanoma treatment with resveratrol. J Surg Res. 172:109–115. 2012. View Article : Google Scholar : PubMed/NCBI
19	Tak JK, Lee JH and Park JW: Resveratrol and piperine enhance radiosensitivity of tumor cells. BMB Rep. 45:242–246. 2012. View Article : Google Scholar : PubMed/NCBI
20	Sakurai H, Suzuki S, Kawasaki N, et al: Tumor necrosis factor-alpha-induced IKK phosphorylation of NF-kappaB p65 on serine 536 is mediated through the TRAF2, TRAF5, and TAK1 signaling pathway. J Biol Chem. 278:36916–36923. 2003. View Article : Google Scholar : PubMed/NCBI
21	Haq R, Yokoyama S, Hawryluk EB, et al: BCL2A1 is a lineage-specific antiapoptotic melanoma oncogene that confers resistance to BRAF inhibition. Proc Natl Acad Sci USA. 110:4321–4326. 2013. View Article : Google Scholar : PubMed/NCBI
22	Trapp V, Parmakhtiar B, Papazian V, Willmott L and Fruehauf JP: Anti-angiogenic effects of resveratrol mediated by decreased VEGF and increased TSP1 expression in melanoma-endothelial cell co-culture. Angiogenesis. 13:305–315. 2010. View Article : Google Scholar : PubMed/NCBI
23	Altieri DC: Survivin, cancer networks and pathway-directed drug discovery. Nat Rev Cancer. 8:61–70. 2008. View Article : Google Scholar : PubMed/NCBI
24	Zhang J, Chiu J, Zhang H, et al: Autophagic cell death induced by resveratrol depends on the Ca(2+)/AMPK/mTOR pathway in A549 cells. Biochem Pharmacol. 86:317–328. 2013. View Article : Google Scholar : PubMed/NCBI
25	Jiang H, Shang X, Wu H, et al: Resveratrol downregulates PI3K/Akt/mTOR signaling pathways in human U251 glioma cells. J Exp Ther Oncol. 8:25–33. 2009.PubMed/NCBI
26	Vaira V, Lee CW, Goel HL, Bosari S, Languino LR and Altieri DC: Regulation of survivin expression by IGF-1/mTOR signaling. Oncogene. 26:2678–2684. 2007. View Article : Google Scholar : PubMed/NCBI
27	Zhao W, Bao P, Qi H and You H: Resveratrol down-regulates survivin and induces apoptosis in human multidrug-resistant SPC-A-1/CDDP cells. Oncol Rep. 23:279–286. 2010.PubMed/NCBI
28	Hayashibara T, Yamada Y, Nakayama S, et al: Resveratrol induces downregulation in survivin expression and apoptosis in HTLV-1-infected cell lines: a prospective agent for adult T cell leukemia chemotherapy. Nutr Cancer. 44:193–201. 2002. View Article : Google Scholar : PubMed/NCBI
29	Shankar S, Siddiqui I and Srivastava RK: Molecular mechanisms of resveratrol (3,4,5-trihydroxy-trans-stilbene) and its interaction with TNF-related apoptosis inducing ligand (TRAIL) in androgen-insensitive prostate cancer cells. Mol Cell Biochem. 304:273–285. 2007. View Article : Google Scholar
30	Singh SK, Moretta D, Almaguel F, Wall NR, De Leon M and De Leon D: Differential effect of proIGF-II and IGF-II on resveratrol induced cell death by regulating survivin cellular localization and mitochondrial depolarization in breast cancer cells. Growth Factors. 25:363–372. 2007. View Article : Google Scholar
31	Singh RP, Tyagi A, Sharma G, Mohan S and Agarwal R: Oral silibinin inhibits in vivo human bladder tumor xenograft growth involving down-regulation of survivin. Clin Cancer Res. 14:300–308. 2008. View Article : Google Scholar : PubMed/NCBI
32	Talantov D, Mazumder A, Yu JX, et al: Novel genes associated with malignant melanoma but not benign melanocytic lesions. Clin Cancer Res. 11:7234–7242. 2005. View Article : Google Scholar : PubMed/NCBI
33	Velculescu VE, Madden SL, Zhang L, et al: Analysis of human transcriptomes. Nat Genet. 23:387–388. 1999. View Article : Google Scholar
34	Adhami VM, Afaq F and Ahmad N: Suppression of ultraviolet B exposure-mediated activation of NF-kappaB in normal human keratinocytes by resveratrol. Neoplasia. 5:74–82. 2003. View Article : Google Scholar : PubMed/NCBI
35	Widlund HR, Horstmann MA, Price ER, et al: Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor. J Cell Biol. 158:1079–1087. 2002. View Article : Google Scholar