Pterostilbene inhibits lung squamous cell carcinoma growth in vitro and in vivo by inducing S phase arrest and apoptosis

Tan,Kok‑Tong; Chen,Ping‑Wen; Li,Shiming; Ke,Te‑Min; Lin,Sheng‑Hao; Yang,Ching‑Chieh

doi:10.3892/ol.2019.10499

Pterostilbene inhibits lung squamous cell carcinoma growth in vitro and in vivo by inducing S phase arrest and apoptosis

Authors:
- Kok‑Tong Tan
- Ping‑Wen Chen
- Shiming Li
- Te‑Min Ke
- Sheng‑Hao Lin
- Ching‑Chieh Yang
View Affiliations

Affiliations: Department of Surgery, Tungs' Taichung Metro Harbor Hospital, Taichung 433, Taiwan, R.O.C., Institute of Biomedical Science, National Chung‑Hsing University, Taichung 402, Taiwan, R.O.C., Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization, Huanggang Normal University, Huanggang, Hubei 438000, P.R. China, Department of Radiation Oncology, Chi‑Mei Medical Center, Tainan 710, Taiwan, R.O.C., Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan, R.O.C.
Published online on: June 19, 2019 https://doi.org/10.3892/ol.2019.10499
Pages: 1631-1640
Copyright: © Tan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

Natural dietary components have become the subject of an increasing amount of interest due to the side effects of anticancer treatment. Pterostilbene, an analog of resveratrol, is primarily found in grapes, and has been suggested to exert antioxidant and anticancer effects in different tumor types. The present study aimed to investigate the antitumor effects and molecular mechanisms of pterostilbene in the human lung squamous cell carcinoma (SqCC) cell line, H520. The results of the present study indicate that pterostilbene significantly reduced cell viability and induced S phase arrest, and that treatment with pterostilbene was associated with the downregulation of cyclin A and cyclin E, as with the upregulation of p21 and p27 expression in H520 cells. In the apoptosis analysis, pterostilbene induced S phase accumulation and the activation of caspase‑3, ‑8 and ‑9 in H520 cells, potentially through the activation of extrinsic and intrinsic apoptotic pathways. Additionally, the in vivo study demonstrated that pterostilbene effectively inhibited lung SqCC growth in a H520 xenograft model. Given the in vitro and in vivo antitumor effects of pterostilbene demonstrated in the present study, pterostilbene may serve a novel and effective therapeutic agent to for patients with SqCC.

View Figures

View References

1	Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI
2	Okamoto T, Suzuki Y, Fujishita T, Kitahara H, Shimamatsu S, Kohno M, Morodomi Y, Kawano D and Maehara Y: The prognostic impact of the amount of tobacco smoking in non-small cell lung cancer-differences between adenocarcinoma and squamous cell carcinoma. Lung Cancer. 85:125–130. 2014. View Article : Google Scholar : PubMed/NCBI
3	Gandara DR, Hammerman PS, Sos ML, Lara PN Jr and Hirsch FR: Squamous cell lung cancer: From tumor genomics to cancer therapeutics. Clin Cancer Res. 21:2236–2243. 2015. View Article : Google Scholar : PubMed/NCBI
4	Yang CC, Fong Y, Lin LC, Que J, Ting WC, Chang CL, Wu HM, Ho CH, Wang JJ and Huang CI: The age-adjusted Charlson comorbidity index is a better predictor of survival in operated lung cancer patients than the Charlson and Elixhauser comorbidity indices. Eur J Cardiothorac Surg. 53:235–240. 2018. View Article : Google Scholar : PubMed/NCBI
5	Ettinger DS, Wood DE, Aisner DL, Akerley W, Bauman J, Chirieac LR, D'Amico TA, DeCamp MM, Dilling TJ, Dobelbower M, et al: Non-small cell lung cancer, version 5.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 15:504–535. 2017. View Article : Google Scholar : PubMed/NCBI
6	Ettinger DS, Akerley W, Borghaei H, Chang AC, Cheney RT, Chirieac LR, D'Amico TA, Demmy TL, Govindan R, Grannis FW Jr, et al: Non-small cell lung cancer, version 2.2013. J Natl Compr Canc Netw. 11:645–653. 2013. View Article : Google Scholar : PubMed/NCBI
7	Shi A, Zhu G, Wu H, Yu R, Li F and Xu B: Analysis of clinical and dosimetric factors associated with severe acute radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent chemotherapy and intensity-modulated radiotherapy. Radiat Oncol. 5:352010. View Article : Google Scholar : PubMed/NCBI
8	Rimando AM, Kalt W, Magee JB, Dewey J and Ballington JR: Resveratrol, pterostilbene, and piceatannol in vaccinium berries. J Agric Food Chem. 52:4713–4719. 2004. View Article : Google Scholar : PubMed/NCBI
9	Estrela JM, Ortega A, Mena S, Rodriguez ML and Asensi M: Pterostilbene: Biomedical applications. Crit Rev Clin Lab Sci. 50:65–78. 2013. View Article : Google Scholar : PubMed/NCBI
10	Xie B, Xu Z, Hu L, Chen G, Wei R, Yang G, Li B, Chang G, Sun X, Wu H, et al: Pterostilbene inhibits human multiple myeloma cells via ERK1/2 and JNK pathway in vitro and in vivo. Int J Mol Sci. 17(pii): E19272016. View Article : Google Scholar : PubMed/NCBI
11	McCormack D and McFadden D: Pterostilbene and cancer: Current review. J Surg Res. 173:e53–e61. 2012. View Article : Google Scholar : PubMed/NCBI
12	Prabhakar CN: Epidermal growth factor receptor in non-small cell lung cancer. Transl Lung Cancer Res. 4:110–118. 2015.PubMed/NCBI
13	Tang Z, Du R, Jiang S, Wu C, Barkauskas DS, Richey J, Molter J, Lam M, Flask C, Gerson S, et al: Dual MET-EGFR combinatorial inhibition against T790M-EGFR-mediated erlotinib-resistant lung cancer. Br J Cancer. 99:911–922. 2008. View Article : Google Scholar : PubMed/NCBI
14	Zhang H, Zhan C, Ke J, Xue Z, Zhang A, Xu K, Shen Z, Yu L and Chen L: EGFR kinase domain mutation positive lung cancers are sensitive to intrapleural perfusion with hyperthermic chemotherapy (IPHC) complete treatment. Oncotarget. 7:3367–3378. 2016.PubMed/NCBI
15	Zhang H, Li N, Chen Y, Huang LY, Wang YC, Fang G, He DC and Xiao XY: Protein profile of human lung squamous carcinoma cell line NCI-H226. Biomed Environ Sci. 20:24–32. 2007.PubMed/NCBI
16	Zang JP and Wei R: Effects of Cx43 gene modification on the proliferation and migration of the human lung squamous carcinoma cell line NCI-H226. Genet Mol Res. 14:13110–13119. 2015. View Article : Google Scholar : PubMed/NCBI
17	Li K, Dias SJ, Rimando AM, Dhar S, Mizuno CS, Penman AD, Lewin JR and Levenson AS: Pterostilbene acts through metastasis-associated protein 1 to inhibit tumor growth, progression and metastasis in prostate cancer. PLoS One. 8:e575422013. View Article : Google Scholar : PubMed/NCBI
18	Mannal PW, Alosi JA, Schneider JG, McDonald DE and McFadden DW: Pterostilbene inhibits pancreatic cancer in vitro. J Gastrointest Surg. 14:873–879. 2010. View Article : Google Scholar : PubMed/NCBI
19	Wang BY, Huang JY, Cheng CY, Lin CH, Ko J and Liaw YP: Lung cancer and prognosis in taiwan: A population-based cancer registry. J Thorac Oncol. 8:1128–1135. 2013. View Article : Google Scholar : PubMed/NCBI
20	Siddiqui IA, Adhami VM, Ahmad N and Mukhtar H: Nanochemoprevention: Sustained release of bioactive food components for cancer prevention. Nutr Cancer. 62:883–890. 2010. View Article : Google Scholar : PubMed/NCBI
21	Riboli E, Slimani N and Kaaks R: Identifiability of food components for cancer chemoprevention. IARC Sci Publ. 23–31. 1996.PubMed/NCBI
22	Suh N, Paul S, Hao X, Simi B, Xiao H, Rimando AM and Reddy BS: Pterostilbene, an active constituent of blueberries, suppresses aberrant crypt foci formation in the azoxymethane-induced colon carcinogenesis model in rats. Clin Cancer Res. 13:350–355. 2007. View Article : Google Scholar : PubMed/NCBI
23	Riche DM, McEwen CL, Riche KD, Sherman JJ, Wofford MR, Deschamp D and Griswold M: Analysis of safety from a human clinical trial with pterostilbene. J Toxicol. 2013:4635952013. View Article : Google Scholar : PubMed/NCBI
24	Pei HL, Mu DM and Zhang B: Anticancer activity of pterostilbene in human ovarian cancer cell lines. Med Sci Monit. 23:3192–3199. 2017. View Article : Google Scholar : PubMed/NCBI
25	Kong Y, Chen G, Xu Z, Yang G, Li B, Wu X, Xiao W, Xie B, Hu L, Sun X, et al: Pterostilbene induces apoptosis and cell cycle arrest in diffuse large B-cell lymphoma cells. Sci Rep. 6:374172016. View Article : Google Scholar : PubMed/NCBI
26	Wawszczyk J, Kapral M, Hollek A and Weglarz L: In vitro evaluation of antiproliferative and cytotoxic properties of pterostilbene against human colon cancer cells. Acta Pol Pharm. 71:1051–1055. 2014.PubMed/NCBI
27	Mann MB and Kaldis P: Cell cycle transitions and Cdk inhibition in melanoma therapy: Cyclin' through the options. Cell Cycle. 10:13492011. View Article : Google Scholar : PubMed/NCBI
28	Aleo E, Henderson CJ, Fontanini A, Solazzo B and Brancolini C: Identification of new compounds that trigger apoptosome-independent caspase activation and apoptosis. Cancer Res. 66:9235–9244. 2006. View Article : Google Scholar : PubMed/NCBI
29	Schneider JG, Alosi JA, McDonald DE and McFadden DW: Pterostilbene inhibits lung cancer through induction of apoptosis. J Surg Res. 161:18–22. 2010. View Article : Google Scholar : PubMed/NCBI
30	Chen RJ, Ho CT and Wang YJ: Pterostilbene induces autophagy and apoptosis in sensitive and chemoresistant human bladder cancer cells. Mol Nutr Food Res. 54:1819–1832. 2010. View Article : Google Scholar : PubMed/NCBI
31	Aral K, Aral CA and Kapila Y: The role of caspase-8, caspase-9, and apoptosis inducing factor in periodontal disease. J Periodontol. 90:288–294. 2019. View Article : Google Scholar : PubMed/NCBI
32	Pan MH, Chang YH, Badmaev V, Nagabhushanam K and Ho CT: Pterostilbene induces apoptosis and cell cycle arrest in human gastric carcinoma cells. J Agric Food Chem. 55:7777–7785. 2007. View Article : Google Scholar : PubMed/NCBI
33	Ruiz MJ, Fernandez M, Pico Y, Mañes J, Asensi M, Carda C, Asensio G and Estrela JM: Dietary administration of high doses of pterostilbene and quercetin to mice is not toxic. J Agric Food Chem. 57:3180–3186. 2009. View Article : Google Scholar : PubMed/NCBI