Piceatannol inhibits proliferation and induces apoptosis of bladder cancer cells through regulation of the PTEN/AKT signal pathway

Xun-gang Li; Wen-sheng Zhang; Xiao-ping Yan

doi:10.14715/cmb/2020.66.3.29

Issue

Vol. 66 No. 3: Issue 3

Issue Published : June 8, 2020

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Piceatannol inhibits proliferation and induces apoptosis of bladder cancer cells through regulation of the PTEN/AKT signal pathway

https://doi.org/10.14715/cmb/2020.66.3.29

Xun-gang Li

Department of Urologic Surgery, The First People's Hospital of Jiu Jiang City of Jiang Xi Province, Jiu Jiang Hospital Affiliated Medical School of Nanchang University, Jiu Jiang City, Jiang Xi Province 332000, China

Wen-sheng Zhang

Xiao-ping Yan

Corresponding Author(s) : Wen-sheng Zhang

mdnym1@163.com

Cellular and Molecular Biology, Vol. 66 No. 3: Issue 3
Article Published : June 5, 2020

Abstract

This study was aimed to investigate the effect of piceatannol (PIC) on the proliferation and apoptosis of bladder cancer cell line EJ, and the underlying mechanism. Bladder cancer cell line EJ was incubated with different concentrations of PIC, and CCK-8 method was used to determine the effect of the treatment on cell proliferation. The effect of PIC on cell cycle, apoptosis and the expressions of related signal pathway proteins were determined using Western blotting. Flow cytometry showed that PIC inhibited the proliferation of EJ cells in a concentration- and time-dependent fashion. Moreover, EJ cells were significantly blocked in G0/G1 phase, when compared with the blank control group (p < 0.05). In addition, PIC enhanced apoptosis of EJ cells in a concentration-dependent manner (p < 0.05). Results from western blotting showed that, compared with the control group, PIC upregulated the protein expression of PTEN, but downregulated Akt protein phosphorylation, relative to control cells. PIC significantly inhibits the proliferation of EJ cells and enhances their apoptosis through a mechanism related to the activation of PTEN/Akt signaling pathway.

Keywords

Bladder cancer Piceatannol PTEN / Akt signaling pathway.

Li, X.- gang, Zhang, W.- sheng, & Yan, X.- ping. (2020). Piceatannol inhibits proliferation and induces apoptosis of bladder cancer cells through regulation of the PTEN/AKT signal pathway. Cellular and Molecular Biology, 66(3), 181–184. https://doi.org/10.14715/cmb/2020.66.3.29

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References

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Nargund VH, Tanabalan C, Kabir M. Management of non–muscle-invasive (superficial) bladder cancer. Semin Oncol 2012; 39: 559-572.
Stein JP, Skinner DG. Radical cystectomy for invasive bladder cancer: long-term results of a standard procedure. World J Urol 2006; 24: 296-304.
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Network CGAR. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 2014; 507: 315.
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Wu P, Cao Z, Wu S. New progress of epigenetic biomarkers in urological cancer. Dis Markers 2016; 2016: 1.
Kasiotis KM, Pratsinis H, Kletsas D, Haroutounian SA. Resveratrol and related stilbenes: their anti-aging and anti-angiogenic properties. Food Chem Toxicol 2013; 61: 112-120.
Piotrowska H, Kucinska M, Murias M. Biological activity of piceatannol: leaving the shadow of resveratrol. Mutat Res 2012; 750: 60-82.
Surh YJ, Na HK. Therapeutic potential and molecular targets of piceatannol in chronic diseases. Adv Exp Med Biol 2016; 928: 185-211.
Schmeel LC, Schmeel FC, Kim Y, Endo T, Lu D, Schmidt-Wolf IG. Targeting the Wnt/beta-catenin pathway in multiple myeloma. Anticancer Res 2013; 33: 4719-4726.
Zhang H, Jia R, Wang C, Hu T, Wang F. Piceatannol promotes apoptosis via up-regulation of microRNA-129 expression in colorectal cancer cell lines. Biochem Biophys Res Commun 2014; 452: 775-781.
Song NR, Hwang MK, Heo YS, Lee KW, Lee HJ. Piceatannol suppresses the metastatic potential of MCF10A human breast epithelial cells harboring mutated H-ras by inhibiting MMP-2 expression. Int J Mol Med 2013; 32: 775-784.
Dias SJ, Li K, Rimando AM, Dhar S, Mizuno CS, Penman AD, et al. Trimethoxy-R esveratrol and Piceatannol Administered Orally Suppress and Inhibit Tumor Formation and Growth in Prostate Cancer Xenografts. Prostate 2013; 73: 1135-1146.
Minakawa M, Miura Y, Yagasaki K. Piceatannol, a resveratrol derivative, promotes glucose uptake through glucose transporter 4 translocation to plasma membrane in L6 myocytes and suppresses blood glucose levels in type 2 diabetic model db/db mice. Biochem Biophys Res Commun 2012; 422: 469-475.
Oritani Y, Okitsu T, Nishimura E, Sai M, Ito T, Takeuchi S. Enhanced glucose tolerance by intravascularly administered piceatannol in freely moving healthy rats. Biochem Biophys Res Commun 2016; 470: 753-758.
Fu Z, Yang J, Wei Y, Li J. Effects of piceatannol and pterostilbene against Î²-amyloid-induced apoptosis on the PI3K/Akt/Bad signaling pathway in PC12 cells. Food Funct 2016; 7: 1014-1023.
Kee HJ, Park S, Kang W, Lim KS, Kim JH, Ahn Y, et al. Piceatannol attenuates cardiac hypertrophy in an animal model through regulation of the expression and binding of the transcription factor GATA binding factor 6. FEBS Lett 2014; 588: 1529-1536.
Lecoeur H, Ledru E, Prevost M, Gougeon M. Strategies for phenotyping apoptotic peripheral human lymphocytes comparing ISNT, annexin-V and 7-AAD cytofluorometric staining methods. J Immunol Methods 1997; 209: 111-123.
El Sayed I, Elkhwsky F, La Vecchia C, Alicandro G. The frequency of bladder cancer in Alexandria, Egypt, over the last two decades. Eur J Cancer Prev 2018; 27: 477-478.
Pei Z, Du X, Song Y, Fan L, Li F, Gao Y, et al. Down-regulation of lncRNA CASC2 promotes cell proliferation and metastasis of bladder cancer by activation of the Wnt/Î²-catenin signaling pathway. Oncotarget 2017; 8: 18145.
Seyed MA, Jantan I, Bukhari SNA, Vijayaraghavan K. A comprehensive review on the chemotherapeutic potential of piceatannol for cancer treatment, with mechanistic insights. J Agric Food Chem 2016; 64: 725-737.
Lee YM, Cho HJ, Seon MR, Kim JK, Lee BY, Park JHY. Piceatannol, a natural stilbene from grapes, induces G1 cell cycle arrest in androgen-insensitive DU145 human prostate cancer cells via the inhibition of CDK activity. Cancer Lett 2009; 285: 166-173.
Lee MS, Jeong MH, Lee HW, Han HJ, Ko A, Hewitt SM, et al. PI3K/AKT activation induces PTEN ubiquitination and destabilization accelerating tumourigenesis. Nat Commun 2015; 6: 7769.
Carnero A, Paramio JM. The PTEN/PI3K/AKT pathway in vivo, cancer mouse models. Front Oncol 2014; 4: 252.
Yu Y, Liang S, Zhou Y, Li S, Li Y, Liao W. HNF1A/CASC2 regulates pancreatic cancer cell proliferation through PTEN/Akt signaling. J Cell Biochem 2019; 120: 2816-2827.
Wang J, Ma W, Liu Y. Long non-coding RNA HULC promotes bladder cancer cells proliferation but inhibits apoptosis via regulation of ZIC2 and PI3K/AKT signaling pathway. Cancer Biomark 2017; 20: 425-434.
Shigematsu Y, Oue N, Nishioka Y, Sakamoto N, Sentani K, Sekino Y, et al. Overexpression of the transmembrane protein BST-2 induces Akt and Erk phosphorylation in bladder cancer. Oncol Lett 2017; 14: 999-1004.

References

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69: 7-34.

Nargund VH, Tanabalan C, Kabir M. Management of non–muscle-invasive (superficial) bladder cancer. Semin Oncol 2012; 39: 559-572.

Stein JP, Skinner DG. Radical cystectomy for invasive bladder cancer: long-term results of a standard procedure. World J Urol 2006; 24: 296-304.

Stenzl A, Cowan NC, De Santis M, Kuczyk MA, Merseburger AS, Ribal MJ, et al. Treatment of muscle-invasive and metastatic bladder cancer: update of the EAU guidelines. Eur Urol 2011; 59: 1009-1018.

Lin T, Ma C. SU-E-J-214: Comparative Assessment On IGRT On Partial Bladder Cancer Treatment Between CT"On"Rails (CTOR) and KV Cone Beam CT (CBCT). Med Physics 2014; 41: 206.

Network CGAR. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 2014; 507: 315.

Li HT, Duymich CE, Weisenberger DJ, Liang G. Genetic and epigenetic alterations in bladder cancer. Int Neurourol J 2016; 20: 84.

Wu P, Cao Z, Wu S. New progress of epigenetic biomarkers in urological cancer. Dis Markers 2016; 2016: 1.

Kasiotis KM, Pratsinis H, Kletsas D, Haroutounian SA. Resveratrol and related stilbenes: their anti-aging and anti-angiogenic properties. Food Chem Toxicol 2013; 61: 112-120.

Piotrowska H, Kucinska M, Murias M. Biological activity of piceatannol: leaving the shadow of resveratrol. Mutat Res 2012; 750: 60-82.

Surh YJ, Na HK. Therapeutic potential and molecular targets of piceatannol in chronic diseases. Adv Exp Med Biol 2016; 928: 185-211.

Schmeel LC, Schmeel FC, Kim Y, Endo T, Lu D, Schmidt-Wolf IG. Targeting the Wnt/beta-catenin pathway in multiple myeloma. Anticancer Res 2013; 33: 4719-4726.

Zhang H, Jia R, Wang C, Hu T, Wang F. Piceatannol promotes apoptosis via up-regulation of microRNA-129 expression in colorectal cancer cell lines. Biochem Biophys Res Commun 2014; 452: 775-781.

Song NR, Hwang MK, Heo YS, Lee KW, Lee HJ. Piceatannol suppresses the metastatic potential of MCF10A human breast epithelial cells harboring mutated H-ras by inhibiting MMP-2 expression. Int J Mol Med 2013; 32: 775-784.

Dias SJ, Li K, Rimando AM, Dhar S, Mizuno CS, Penman AD, et al. Trimethoxy-R esveratrol and Piceatannol Administered Orally Suppress and Inhibit Tumor Formation and Growth in Prostate Cancer Xenografts. Prostate 2013; 73: 1135-1146.

Minakawa M, Miura Y, Yagasaki K. Piceatannol, a resveratrol derivative, promotes glucose uptake through glucose transporter 4 translocation to plasma membrane in L6 myocytes and suppresses blood glucose levels in type 2 diabetic model db/db mice. Biochem Biophys Res Commun 2012; 422: 469-475.

Oritani Y, Okitsu T, Nishimura E, Sai M, Ito T, Takeuchi S. Enhanced glucose tolerance by intravascularly administered piceatannol in freely moving healthy rats. Biochem Biophys Res Commun 2016; 470: 753-758.

Fu Z, Yang J, Wei Y, Li J. Effects of piceatannol and pterostilbene against Î²-amyloid-induced apoptosis on the PI3K/Akt/Bad signaling pathway in PC12 cells. Food Funct 2016; 7: 1014-1023.

Kee HJ, Park S, Kang W, Lim KS, Kim JH, Ahn Y, et al. Piceatannol attenuates cardiac hypertrophy in an animal model through regulation of the expression and binding of the transcription factor GATA binding factor 6. FEBS Lett 2014; 588: 1529-1536.

Lecoeur H, Ledru E, Prevost M, Gougeon M. Strategies for phenotyping apoptotic peripheral human lymphocytes comparing ISNT, annexin-V and 7-AAD cytofluorometric staining methods. J Immunol Methods 1997; 209: 111-123.

El Sayed I, Elkhwsky F, La Vecchia C, Alicandro G. The frequency of bladder cancer in Alexandria, Egypt, over the last two decades. Eur J Cancer Prev 2018; 27: 477-478.

Pei Z, Du X, Song Y, Fan L, Li F, Gao Y, et al. Down-regulation of lncRNA CASC2 promotes cell proliferation and metastasis of bladder cancer by activation of the Wnt/Î²-catenin signaling pathway. Oncotarget 2017; 8: 18145.

Seyed MA, Jantan I, Bukhari SNA, Vijayaraghavan K. A comprehensive review on the chemotherapeutic potential of piceatannol for cancer treatment, with mechanistic insights. J Agric Food Chem 2016; 64: 725-737.

Lee YM, Cho HJ, Seon MR, Kim JK, Lee BY, Park JHY. Piceatannol, a natural stilbene from grapes, induces G1 cell cycle arrest in androgen-insensitive DU145 human prostate cancer cells via the inhibition of CDK activity. Cancer Lett 2009; 285: 166-173.

Lee MS, Jeong MH, Lee HW, Han HJ, Ko A, Hewitt SM, et al. PI3K/AKT activation induces PTEN ubiquitination and destabilization accelerating tumourigenesis. Nat Commun 2015; 6: 7769.

Carnero A, Paramio JM. The PTEN/PI3K/AKT pathway in vivo, cancer mouse models. Front Oncol 2014; 4: 252.

Yu Y, Liang S, Zhou Y, Li S, Li Y, Liao W. HNF1A/CASC2 regulates pancreatic cancer cell proliferation through PTEN/Akt signaling. J Cell Biochem 2019; 120: 2816-2827.

Wang J, Ma W, Liu Y. Long non-coding RNA HULC promotes bladder cancer cells proliferation but inhibits apoptosis via regulation of ZIC2 and PI3K/AKT signaling pathway. Cancer Biomark 2017; 20: 425-434.

Shigematsu Y, Oue N, Nishioka Y, Sakamoto N, Sentani K, Sekino Y, et al. Overexpression of the transmembrane protein BST-2 induces Akt and Erk phosphorylation in bladder cancer. Oncol Lett 2017; 14: 999-1004.

Author biographies is not available.