Dihydromyricetin induces cell cycle arrest and apoptosis in melanoma SK-MEL-28 cells

Zeng,Guofang; Liu,Jie; Chen,Hege; Liu,Bin; Zhang,Qingyu; Li,Mingyi; Zhu,Runzhi

doi:10.3892/or.2014.3160

Dihydromyricetin induces cell cycle arrest and apoptosis in melanoma SK-MEL-28 cells

Authors:
- Guofang Zeng
- Jie Liu
- Hege Chen
- Bin Liu
- Qingyu Zhang
- Mingyi Li
- Runzhi Zhu
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Affiliations: Zhanjiang Key Laboratory of Hepatobiliary Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China, Laboratory of Urology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China
Published online on: April 25, 2014 https://doi.org/10.3892/or.2014.3160
Pages: 2713-2719

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Abstract

Dihydromyricetin (DHM) exhibits multiple pharmacological activities; however, the role of DHM in anti-melanoma activities and the underlying molecular mechanisms are unclear. The aim of the present study was to evaluate the effects of DHM on cell proliferation, cell cycle distribution and apoptosis in the human melanoma SK-MEL-28 cell line, and to explore the related mechanisms. The effect of DHM on cell proliferation was investigated by MTT assay, and cell cycle distribution was determined by flow cytometry. TUNEL assay was used to evaluate DHM-mediated apoptosis, and western blotting was applied to examine expression levels of p53, p21, Cdc25A, Cdc2, P-Cdc2, Bax, IKK-α, NF-κB p65, p38 and P-p38 proteins. The results revealed that DHM suppressed cell proliferation of SK-MEL-28 cells in a concentration- and time-dependent manner, and caused cell cycle arrest at the G1/S phase. DHM increased the production of p53 and p21 proteins and downregulated the production of Cdc25A, Cdc2 and P-Cdc2 proteins, which induced cell cycle arrest. Additionally, DHM significantly induced the apoptosis of SK-MEL-28 cells, and enhanced the expression levels of Bax proteins and decreased the protein levels of IKK-α, NF-κB (p65) and P-p38. The results suggest that DHM may be a novel and effective candidate agent to inhibit the growth of melanoma.

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1	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 62:10–29. 2012. View Article : Google Scholar
2	Gray-Schopfer V, Wellbrock C and Marais R: Melanoma biology and new targeted therapy. Nature. 445:851–857. 2007. View Article : Google Scholar : PubMed/NCBI
3	Miller AJ and Mihm MC Jr: Melanoma. N Engl J Med. 355:51–65. 2006. View Article : Google Scholar
4	Korn EL, Liu PY, Lee SJ, et al: Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials. J Clin Oncol. 26:527–534. 2008. View Article : Google Scholar : PubMed/NCBI
5	He GX, Pei G, Zhou TD and Zhou XX: Determination of total flavonoids and dihydromyricetin in Ampelopsis grossedentala(Hand-Mazz) (W.T. Wang). Zhongguo Zhong Yao Za Zhi. 25:423–425. 2000.(In Chinese).
6	Du Q, Cai W, Xia M and Ito Y: Purification of (+)-dihydromyricetin from leaves extract of Ampelopsis grossedentata using high-speed countercurrent chromatograph with scale-up triple columns. J Chromatogr A. 973:217–220. 2002.
7	Wang Y, Zhou L, Li R and Wang Y: Determination of ampelopsin in the different parts of Ampelopsis grossedentata in different seasons by RP-HPLC. Zhong Yao Cai. 25:23–24. 2002.(In Chinese).
8	Murakami T, Miyakoshi M, Araho D, et al: Hepatoprotective activity of tocha, the stems and leaves of Ampelopsis grossedentata, and ampelopsin. Biofactors. 21:175–178. 2004. View Article : Google Scholar : PubMed/NCBI
9	Shen Y, Lindemeyer AK, Gonzalez C, Shao XM, Spigelman I, OIsen RW and Liang J: Dihydromyricetin as a novel anti-alcohol intoxication medication. J Neurosci. 32:390–401. 2012. View Article : Google Scholar : PubMed/NCBI
10	Zhang YS, Ning ZX, Yang SZ and Wu H: Antioxidation properties and mechanism of action of dihydromyricetin from Ampelopsis grossedentata. Yao Xue Xue Bao. 38:241–244. 2003.PubMed/NCBI
11	He G, Du F, Yang W, Pei G and Zhu Y: Effects of tengcha flavonoids on scavenging oxygen free radicals and inhibiting lipid-peroxidation. Zhong Yao Cai. 26:338–340. 2003.(In Chinese).
12	Zhong ZX, Qin JP, Zhou GF and Chen XF: Experimental studies of hypoglycemic action on total flavone of Ampelopsis grossedentata from Guangxi. Zhongguo Zhong Yao Za Zhi. 27:687–689. 2002.(In Chinese).
13	Qi S, Xin Y, Guo Y, Diao Y, Kou X, Luo L and Yin Z: Ampelopsin reduces endotoxic inflammation via repressing ROS-mediated activation of PI3K/Akt/NF-κB signaling pathways. Int Immunopharmacol. 12:278–287. 2012.PubMed/NCBI
14	Ni F, Gong Y, Li L, Abdolmaleky HM and Zhou JR: Flavonoid Ampelopsin inhibits the growth and metastasis of prostate cancer in vitro and in mice. PloS One. 7:e388022012. View Article : Google Scholar : PubMed/NCBI
15	Zhang B, Dong S, Cen X, et al: Ampelopsin sodium exhibits antitumor effects against bladder carcinoma in orthotopic xenograft models. Anticancer Drugs. 23:590–596. 2012. View Article : Google Scholar : PubMed/NCBI
16	Zeng S, Liu D, Ye Y, Wang L and Wang W: Anti-tumor effects of ampelopsin on human lung cancer GLC-82 implanted in nude mice. Zhong Yao Cai. 27:842–845. 2004.(In Chinese).
17	Gao Q, Yang X and Ou M: Effect of serum containing tengcha total flavonoid and dihydromyricetin on proliferation and apoptosis of HepG2 cells. Zhongguo Zhong Yao Za Zhi. 36:500–503. 2011.(In Chinese).
18	Luo GQ, Zeng S and Liu DY: Inhibitory effects of ampelopsin on angiogenesis. Zhong Yao Cai. 29:146–150. 2006.(In Chinese).
19	Liu D and Luo M: Study on inhibitory effect of ampelopsin on melanoma by serologic pharmacological method. Zhong Yao Cai. 24:348–350. 2001.(In Chinese).
20	Zheng HQ and Liu DY: Anti-invasive and anti-metastatic effect of ampelopsin on melanoma. Ai Zheng. 22:363–367. 2003.(In Chinese).
21	Liu DY, Zheng HQ and Luo GQ: Effects of ampelopsin on invasion and metastasis of B16 mouse melanoma in vivo and in vitro. Zhongguo Zhong Yao Za Zhi. 28:957–961. 2003.(In Chinese).
22	Massaoka MH, Matsuo AL, Figueiredo CR, et al: Jacaranone induces apoptosis in melanoma cells via ROS-mediated downregulation of Akt and p38 MAPK Activation and displays antitumor activity in vivo. PLoS One. 7:e386982012. View Article : Google Scholar : PubMed/NCBI
23	Crighton D, Wilkinson S, O’Prey J, et al: DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Cell. 126:121–134. 2006. View Article : Google Scholar : PubMed/NCBI
24	Ferlay J, Parkin DM and Steliarova-Founcher E: Estimates of cancer incidence and mortatlity in Europe in 2008. Eur J Cancer. 46:765–781. 2010. View Article : Google Scholar : PubMed/NCBI
25	Sondak VK, Sabel MS and Mulé JJ: Allogeneic and autologous melanoma vaccines: where have we been and where are we going? Clin Cancer Res. 12:2337s–2341s. 2006. View Article : Google Scholar : PubMed/NCBI
26	Garbe C, Peris K, Hauschild A, et al: Diagnosis and treatment of melanoma: European Consensus-based interdisciplinary guideline. Eur J Cancer. 46:270–283. 2010. View Article : Google Scholar : PubMed/NCBI
27	Kruse JP and Gu W: Modes of p53 regulation. Cell. 137:609–622. 2009. View Article : Google Scholar
28	Tang Y, Luo J, Zhang W and Gu W: Tip60-dependent acetylation of p53 modulates the decision between cell-cycle arrest and apoptosis. Mol Cell. 24:827–839. 2006. View Article : Google Scholar : PubMed/NCBI
29	Sykes SM, Mellert HS, Holbert MA, Li K, Marmorstein R, Lane WS and McMahon SB: Acetylation of the p53 DNA-binding domain regulates apoptosis induction. Mol Cell. 24:841–851. 2006. View Article : Google Scholar : PubMed/NCBI
30	Armstrong MJ, Stang MT, Liu Y, et al: Interferon regulatory factor 1 (IRF-1) induces p21W^AF1/CIP1 dependent cell cycle arrest and p21^WAF1/CIP1 independent modulation of suivivin in cancer cells. Cancer Lett. 319:56–65. 2012. View Article : Google Scholar : PubMed/NCBI
31	Tu Ys, Kang XL, Zhou JG, Lv XF, Tang YB and Guan YY: Involvement of Chk1-Cdc25A-cyclin A/CDK2 pathway in simvastatin induced S-phase cell cycle arrest and apoptosis in multiple myeloma cells. Eur J Pharmacol. 670:356–364. 2011. View Article : Google Scholar : PubMed/NCBI
32	Bonnefont J, Laforge T, Plastre O, Beck B, Sorce S, Dehay C and Krause KH: Primate-specific RFPL1 gene controls cell-cycle progression through cyclin B1/Cdc2 degradation. Cell Death Differ. 18:293–303. 2011.
33	Watanabe G, Behrns KE, Kim JS and Kim RD: Heat shock protein 90 inhibition abrogates hepatocellular cancer growth through cdc2-mediated G₂/M cell cycle arrest and apoptosis. Cancer Chemother Pharmacol. 64:433–443. 2009. View Article : Google Scholar : PubMed/NCBI
34	Yonish-Rouach E, Resnitzky D, Lotem J, Sachs L, Kimchi A and Oren M: Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6. Nature. 352:345–357. 1991. View Article : Google Scholar : PubMed/NCBI
35	Donauer J, Schreck I, Liebel U and Weiss C: Role and interaction of p53, BAX and the stress-activated protein kinases p38 and JNK in benzo(a)pyrene-diolepoxide induced apoptosis in human colon carcinoma cells. Arch Toxical. 86:329–337. 2012. View Article : Google Scholar
36	Tomita Y, Marchenko N, Erster S, et al: WT p53, but not tumor-derived mutants, bind to Bcl2 via the DNA binding domain and induce mitochondrial permeabilization. J Biol Chem. 281:8600–8606. 2006. View Article : Google Scholar : PubMed/NCBI
37	Qin JZ, Ziffra J, Stennett L, Bodner B, Bonish BK, Chaturvedi V, et al: Proteasome inhibitors trigger NOXA-mediated apoptosis in melanoma and myeloma cells. Cancer Res. 65:6282–6293. 2005. View Article : Google Scholar : PubMed/NCBI
38	Escárcega RO, Fuentes-Alexandro S, Garcı́a-Carrasco M, Gatica A and Zamora A: The transcription factor nuclear factor-kappa B and cancer. Clin Oncol. 19:154–161. 2007.
39	Uchida S, Yoshioka K, Kizu R, et al: Stress-activated mitogen-activated protein kinase c-Jun NH2-terminal kinase and p38 target Cdc25B for degradation. Cancer Res. 69:6438–6444. 2009. View Article : Google Scholar : PubMed/NCBI