Polydatin inhibits growth of lung cancer cells by inducing apoptosis and causing cell cycle arrest

Zhang,Yusong; Zhuang,Zhixiang; Meng,Qinghui; Jiao,Yang; Xu,Jiaying; Fan,Saijun

doi:10.3892/ol.2013.1696

Polydatin inhibits growth of lung cancer cells by inducing apoptosis and causing cell cycle arrest

Authors:
- Yusong Zhang
- Zhixiang Zhuang
- Qinghui Meng
- Yang Jiao
- Jiaying Xu
- Saijun Fan
View Affiliations

Affiliations: Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China, Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA, School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China
Published online on: November 21, 2013 https://doi.org/10.3892/ol.2013.1696
Pages: 295-301

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

Polydatin (PD), a small natural compound from Polygonum cuspidatum, has a number of biological functions. However, the anticancer activity of PD has been poorly investigated. In the present study, thiazolyl blue tetrazolium bromide assay was used to evaluate the inhibitory effect of PD on cell growth. Cell cycle distribution and apoptosis were investigated by flow cytometry. In addition, the expression of several proteins associated with apoptosis and cell cycle were analyzed by western blot analysis. The results demonstrated that PD significantly inhibits the proliferation of A549 and NCI‑H1975 lung cancer cell lines and causes dose‑dependent apoptosis. Cell cycle analysis revealed that PD induces S phase cell cycle arrest. Western blot analysis showed that the expression of Bcl‑2 decreased as that of Bax increased, and the expression of cyclin D1 was also suppressed. The results suggest that PD has potential therapeutic applications in the treatment of lung cancer.

View Figures

View References

1	Spiro SG, Tanner NT, Silvestri GA, et al: Lung cancer: progress in diagnosis, staging and therapy. Respirology. 15:44–50. 2010. View Article : Google Scholar : PubMed/NCBI
2	Stinchcombe TE, Fried D, Morris DE and Socinski MA: Combined modality therapy for stage III non-small cell lung cancer. Oncologist. 11:809–823. 2006. View Article : Google Scholar : PubMed/NCBI
3	Luan J, Duan H, Liu Q, Yagasaki K and Zhang G: Inhibitory effects of norcantharidin against human lung cancer cell growth and migration. Cytotechnology. 62:349–355. 2010. View Article : Google Scholar : PubMed/NCBI
4	Newman DJ and Cragg GM: Natural products as sources of new drugs over the last 25 years. J Nat Prod. 70:461–477. 2007.PubMed/NCBI
5	Cragg GM and Newman DJ: Plants as a source of anti-cancer agents. J Ethnopharmacol. 100:72–79. 2005.
6	Gordaliza M: Natural products as leads to anticancer drugs. Clin Transl Oncol. 9:767–776. 2007. View Article : Google Scholar : PubMed/NCBI
7	Zhao KS, Jin C, Huang X, et al: The mechanism of Polydatin in shock treatment. Clin Hemorheol Microcirc. 29:211–217. 2003.PubMed/NCBI
8	Wang X, Song R, Chen Y, Zhao M and Zhao KS: Polydatin - a new mitochondria protector for acute severe hemorrhagic shock treatment. Expert Opin Investig Drugs. 22:169–179. 2013. View Article : Google Scholar : PubMed/NCBI
9	Wang X, Song R, Bian HN, Brunk UT, Zhao M and Zhao KS: Polydatin, a natural polyphenol, protects arterial smooth muscle cells against mitochondrial dysfunction and lysosomal destabilization following hemorrhagic shock. Am J Physiol Regul Integr Comp Physiol. 302:R805–R814. 2012. View Article : Google Scholar
10	Cheng Y, Zhang HT, Sun L, et al: Involvement of cell adhesion molecules in polydatin protection of brain tissues from ischemia-reperfusion injury. Brain Res. 1110:193–200. 2006. View Article : Google Scholar : PubMed/NCBI
11	Miao Q, Wang S, Miao S, Wang J, Xie Y and Yang Q: Cardioprotective effect of polydatin against ischemia/reperfusion injury: roles of protein kinase C and mito K(ATP) activation. Phytomedicine. 19:8–12. 2011. View Article : Google Scholar : PubMed/NCBI
12	Gao JP, Chen CX, Gu WL, Wu Q, Wang Y and Lü J: Effects of polydatin on attenuating ventricular remodeling in isoproterenol-induced mouse and pressure-overload rat models. Fitoterapia. 81:953–960. 2010. View Article : Google Scholar : PubMed/NCBI
13	Indraccolo U and Barbieri F: Effect of palmitoylethanolamide-polydatin combination on chronic pelvic pain associated with endometriosis: preliminary observations. Eur J Obstet Gynecol Reprod Biol. 150:76–79. 2010. View Article : Google Scholar
14	Fan S, Wang JA, Yuan RQ, et al: BRCA1 as a potential human prostate tumor suppressor: modulation of proliferation, damage responses and expression of cell regulatory proteins. Oncogene. 16:3069–3082. 1998. View Article : Google Scholar
15	Vermes I, Haanen C, Steffens-Nakken H and Reutelingsperger C: A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J Immunol Methods. 184:39–51. 1995. View Article : Google Scholar
16	Fan S, Gao M, Meng Q, et al: Role of NF-kappaB signaling in hepatocyte growth factor/scatter factor-mediated cell protection. Oncogene. 24:1749–1766. 2005. View Article : Google Scholar : PubMed/NCBI
17	Xu JY, Meng QH, Chong Y, et al: Sanguinarine inhibits growth of human cervical cancer cells through the induction of apoptosis. Oncol Rep. 28:2264–2270. 2012.PubMed/NCBI
18	Hollman PC, de Vries JH, van LSD, Mengelers MJ and Katan MB: Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers. Am J Clin Nutr. 62:1276–1282. 1995.PubMed/NCBI
19	Paganga G and Rice-Evans CA: The identification of flavonoids as glycosides in human plasma. FEBS Lett. 401:78–82. 1997. View Article : Google Scholar : PubMed/NCBI
20	Regev-Shoshani G, Shoseyov O, Bilkis I and Kerem Z: Glycosylation of resveratrol protects it from enzymic oxidation. Biochem J. 374:157–163. 2003. View Article : Google Scholar : PubMed/NCBI
21	Krasnow MN and Murphy TM: Polyphenol glucosylating activity in cell suspensions of grape (Vitis vinifera). J Agric Food Chem. 52:3467–3472. 2004. View Article : Google Scholar : PubMed/NCBI
22	Jang M, Cai L, Udeani GO, et al: Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 275:218–220. 1997. View Article : Google Scholar : PubMed/NCBI
23	Joe AK, Liu H, Suzui M, Vural ME, Xiao D and Weinstein IB: Resveratrol induces growth inhibition, S-phase arrest, apoptosis, and changes in biomarker expression in several human cancer cell lines. Clin Cancer Res. 8:893–903. 2002.
24	Rezk YA, Balulad SS, Keller RS and Bennett JA: Use of resveratrol to improve the effectiveness of cisplatin and doxorubicin: study in human gynecologic cancer cell lines and in rodent heart. Am J Obstet Gynecol. 194:e23–e26. 2006. View Article : Google Scholar : PubMed/NCBI
25	Liu PL, Tsai JR, Charles AL, et al: Resveratrol inhibits human lung adenocarcinoma cell metastasis by suppressing heme oxygenase 1-mediated nuclear factor-kappaB pathway and subsequently downregulating expression of matrix metalloproteinases. Mol Nutr Food Res. 54(Suppl 2): S196–S204. 2010. View Article : Google Scholar
26	Shibata MA, Akao Y, Shibata E, et al: Vaticanol C, a novel resveratrol tetramer, reduces lymph node and lung metastases of mouse mammary carcinoma carrying p53 mutation. Cancer Chemother Pharmacol. 60:681–691. 2007. View Article : Google Scholar
27	Liu HS, Pan CE, Yang W and Liu XM: Antitumor and immunomodulatory activity of resveratrol on experimentally implanted tumor of H22 in Balb/c mice. World J Gastroenterol. 9:1474–1476. 2003.PubMed/NCBI
28	Zhou HB, Chen JJ, Wang WX, Cai JT and Du Q: Anticancer activity of resveratrol on implanted human primary gastric carcinoma cells in nude mice. World J Gastroenterol. 11:280–284. 2005. View Article : Google Scholar : PubMed/NCBI
29	Pan MH, Gao JH, Lai CS, et al: Antitumor activity of 3,5,4′-trimethoxystilbene in COLO 205 cells and xenografts in SCID mice. Mol Carcinog. 47:184–196. 2008.
30	Li T, Fan GX, Wang W, Li T and Yuan YK: Resveratrol induces apoptosis, influences IL-6 and exerts immunomodulatory effect on mouse lymphocytic leukemia both in vitro and in vivo. Int Immunopharmacol. 7:1221–1231. 2007. View Article : Google Scholar
31	Chen JC, Chen Y, Lin JH, Wu JM and Tseng SH: Resveratrol suppresses angiogenesis in gliomas: evaluation by color Doppler ultrasound. Anticancer Res. 26:1237–1245. 2006.PubMed/NCBI
32	Wyllie AH: Apoptosis: an overview. Br Med Bull. 53:451–465. 1997. View Article : Google Scholar
33	Neto CC, Amoroso JW and Liberty AM: Anticancer activities of cranberry phytochemicals: an update. Mol Nutr Food Res. 52(Suppl 1): S18–S27. 2008.PubMed/NCBI
34	Kaur M and Agarwal R: Transcription factors: molecular targets for prostate cancer intervention by phytochemicals. Curr Cancer Drug Targets. 7:355–367. 2007. View Article : Google Scholar : PubMed/NCBI
35	Yang J, Liu X, Bhalla K, et al: Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science. 275:1129–1132. 1997. View Article : Google Scholar : PubMed/NCBI
36	Kluck RM, Bossy-Wetzel E, Green DR and Newmeyer DD: The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science. 275:1132–1136. 1997. View Article : Google Scholar : PubMed/NCBI
37	Graña X and Reddy EP: Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene. 11:211–219. 1995.PubMed/NCBI
38	Pavletich NP: Mechanisms of cyclin-dependent kinase regulation: structures of Cdks, their cyclin activators, and Cip and INK4 inhibitors. J Mol Biol. 287:821–828. 1999. View Article : Google Scholar : PubMed/NCBI
39	Alao JP: The regulation of cyclin D1 degradation: roles in cancer development and the potential for therapeutic invention. Mol Cancer. 6:242007. View Article : Google Scholar : PubMed/NCBI
40	Gillett C, Smith P, Gregory W, et al: Cyclin D1 and prognosis in human breast cancer. Int J Cancer. 69:92–99. 1996. View Article : Google Scholar : PubMed/NCBI
41	Hall M and Peters G: Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer. Adv Cancer Res. 68:67–108. 1996. View Article : Google Scholar : PubMed/NCBI
42	Molenaar JJ, Ebus ME, Koster J, et al: Cyclin D1 and CDK4 activity contribute to the undifferentiated phenotype in neuroblastoma. Cancer Res. 68:2599–2609. 2008. View Article : Google Scholar : PubMed/NCBI
43	Yang K, Hitomi M and Stacey DW: Variations in cyclin D1 levels through the cell cycle determine the proliferative fate of a cell. Cell Div. 1:322006. View Article : Google Scholar : PubMed/NCBI