Pachymic acid inhibits growth and induces cell cycle arrest and apoptosis in gastric cancer SGC‑7901 cells

Sun,Kuan‑Xue; Xia,Hong‑Wei

doi:10.3892/ol.2018.8899

Pachymic acid inhibits growth and induces cell cycle arrest and apoptosis in gastric cancer SGC‑7901 cells

Authors:
- Kuan‑Xue Sun
- Hong‑Wei Xia
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Affiliations: Department of General Surgery, Gong Li Hospital of Shanghai Pu Dong New District, Shanghai 200135, P.R. China, Department of Ultrasound, Gong Li Hospital of Shanghai Pu Dong New District, Shanghai 200135, P.R. China
Published online on: June 5, 2018 https://doi.org/10.3892/ol.2018.8899
Pages: 2517-2524

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Abstract

The aim of the present study was to elucidate the anticancer effect of pachymic acid (PA) in gastric cancer SGC‑7901 cells and the potential molecular mechanisms involved. Cell Count kit‑8 assay was performed to examine the effect of PA on the cell proliferation of SGC‑7901 cells. Cell cycle, cell apoptosis, mitochondria membrane potential (Dψm) and reactive oxygen species (ROS) analysis were assessed by flow cytometry, respectively. DNA fragmentation assay was performed by Hoechst 33258 staining. Western blotting was performed to detect the effect of various concentrations of PA on the levels of BCL2 associated X protein (Bax) expression as well as B‑cell lymphoma 2 (Bcl‑2), cytochrome C (cyt‑c) and caspase‑3 in SGC‑7901 cells. It was demonstrated that PA was able to significantly inhibit the viability and induce G0/G1 cell cycle arrest of SGC‑7901 cells in a concentration‑dependent manner. The apoptotic rate and ROS generation were markedly increased, while Dψm was decreased following the treatment of SGC‑7901 cells with various concentrations of PA. Moreover, the expression of Bax, cytochrome c and caspase‑3 were markedly increased and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) was significantly inactivated and BCL‑2 expression was decreased following PA treatment in SGC‑7901 cells. Notably, JAK2 inhibitor (AG490) mimics the effects of PA on the viability and apoptosis of SGC‑7901 cells. Further in vivo study indicated that treatment with PA significantly inhibited the growth of tumor in nude mice that were transplanted with SGC‑7901 cells in a concentration‑dependent manner. These results may advance the current understanding of the anticancer mechanisms of PA in gastric cancer.

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1	Aggarwal A, Guo DL, Hoshida Y, Yuen ST, Chu KM, So S, Boussioutas A, Chen X, Bowtell D, Aburatani H, et al: Topological and functional discovery in a gene coexpression meta-network of gastric cancer. Cancer Res. 66:232–241. 2006. View Article : Google Scholar : PubMed/NCBI
2	Giordano A and Cito L: Advances in gastric cancer prevention. World J Clin Oncol. 3:128–136. 2012. View Article : Google Scholar : PubMed/NCBI
3	Islami F and Kamangar F: Helicobacter pylori and esophageal cancer risk: A meta-analysis. Cancer Prev Res (Phila). 1:329–338. 2008. View Article : Google Scholar : PubMed/NCBI
4	Kamangar F, Qiao YL, Blaser MJ, Sun XD, Katki H, Fan JH, Perez-Perez GI, Abnet CC, Zhao P, Mark SD, et al: Helicobacter pylori and oesophageal and gastric cancers in a prospective study in China. Br J Cancer. 96:172–176. 2007. View Article : Google Scholar : PubMed/NCBI
5	Zheng L, Wu C, Xi P, Zhu M, Zhang L, Chen S, Li X, Gu J and Zheng Y: The survival and the long-term trends of patients with gastric cancer in Shanghai, China. BMC Cancer. 14:3002014. View Article : Google Scholar : PubMed/NCBI
6	Ko JK, Leung WC, Ho WK and Chiu P: Herbal diterpenoidsinduce growth arrest and apoptosis in colon cancer cells with increased expression of the nonsteroidal anti-inflammatory drug-activated gene. Eur J Pharmacol. 559:1–13. 2007. View Article : Google Scholar : PubMed/NCBI
7	Yen CY, Chiu CC, Chang FR, Chen JY, Hwang CC, Hseu YC, Yang HL, Lee AY, Tsai MT, Guo ZL, et al: 4beta-Hydroxywithanolide E from Physalisperuviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest. BMC Cancer. 10:462010. View Article : Google Scholar : PubMed/NCBI
8	Shiezadeh F, Mousavi SH, Amiri MS, Iranshahi M, Tayarani-Najaran Z and Karimi G: Cytotoxic and apoptotic potential of Rheum turkestanicumJanisch root extract on human cancer and normal cells. Iran J Pharm Res. 12:811–819. 2013.PubMed/NCBI
9	Rajput S, Kumar BP, Dey KK, Pal I, Parekh A and Mandal M: Molecular targeting of Akt by thymoquinone promotes G 1 arrest through translation inhibition of cyclin D1 and induces apoptosis in breast cancer cells. Life Sci. 93:783–790. 2013. View Article : Google Scholar : PubMed/NCBI
10	Cheng S, Eliaz I, Lin J, Thyagarajan-Sahu A and Sliva D: Triterpenes from Poria cocos suppress growth and invasiveness of pancreatic cancer cells through the downregulation of MMP-7. Int J Oncol. 42:1869–1874. 2013. View Article : Google Scholar : PubMed/NCBI
11	Ma J, Liu J, Lu C and Cai D: Pachymic acid induces apoptosis via activating ROS-dependent JNK and ER stress pathways in lung cancer cells. Cancer Cell Int. 15:782015. View Article : Google Scholar : PubMed/NCBI
12	Gapter L, Wang Z, Glinski J and Ng KY: Induction of apoptosis in prostate cancer cells by pachymic acid from Poriacocos. Biochem Biophys Res Commun. 332:1153–1161. 2005. View Article : Google Scholar : PubMed/NCBI
13	Huang YC, Chang WL, Huang SF, Lin CY, Lin HC and Chang TC: Pachymic acid stimulates glucose uptake through enhanced GLUT4 expression and translocation. Eur J Pharmacol. 648:39–49. 2010. View Article : Google Scholar : PubMed/NCBI
14	Tomayko MM and Reynolds CP: Determination of subcutaneous tumor size in athymic (nude) mice. Cancer Chemother Pharmacol. 24:148–154. 1989. View Article : Google Scholar : PubMed/NCBI
15	Ly JD, Grubb D and Lawen A: The mitochondrial membrane potential (deltapsi(m)) in apoptosis; an update. Apoptosis. 8:115–128. 2003. View Article : Google Scholar : PubMed/NCBI
16	Qu K, Shen NY, Xu XS, Su HB, Wei JC, Tai MH, Meng FD, Zhou L, Zhang YL and Liu C: Emodin induces human T cell apoptosis in vitro by ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction. Acta Pharmacol Sin. 34:1217–1228. 2013. View Article : Google Scholar : PubMed/NCBI
17	Hong R, Shen MH, Xie XH and Ruan SM: Inhibition of breast cancer metastasis via PITPNM3 by pachymic acid. Asian Pac J Cancer Prev. 13:1877–1880. 2012. View Article : Google Scholar : PubMed/NCBI
18	Ling H, Zhang Y, Ng KY and Chew EH: Pachymic acid impairs breast cancer cell invasion by suppressing nuclear factor-κB-dependent matrix metalloproteinase-9 expression. Breast Cancer Res Treat. 126:609–620. 2011. View Article : Google Scholar : PubMed/NCBI
19	King K and Cidlowski J: Cell cycle regulation and apoptosis. Ann Rev Physiol. 60:601–617. 1998. View Article : Google Scholar
20	Chen Y, Lian P, Liu Y and Xu K: Pachymic acid inhibits tumorigenesis in gallbladder carcinoma cells. Int J Clin Exp Med. 8:17781–17788. 2015.PubMed/NCBI
21	Curtin JF, Donovan M and Cotter TG: Regulation and measurement of oxidative stress in apoptosis. J Immunol Methods. 265:49–72. 2002. View Article : Google Scholar : PubMed/NCBI
22	Herrera B, Fernández M, Alvarez AM, Roncero C, Benito M, Gil J and Fabregat I: Activation of caspases occurs downstream from radical oxygen species production, Bcl-xL down-regulation, and early cytochrome C release in apoptosis induced by transforming growth factor beta in rat fetal hepatocytes. Hepatology. 34:548–556. 2001. View Article : Google Scholar : PubMed/NCBI
23	Green DR and Chipuk JE: Apoptosis: Stabbed in the BAX. Nature. 455:1047–1049. 2008. View Article : Google Scholar : PubMed/NCBI
24	Zhu X, Zhang K, Wang Q, Chen S, Gou Y, Cui Y and Li Q: Cisplatin-mediated c-myc overexpression and cytochrome c (cyt c) release result in the up-regulation of the death receptors DR4 and DR5 and the activation of caspase 3 and caspase 9, likely responsible for the TRAIL-sensitizing effect of cisplatin. Med Oncol. 32:1332015. View Article : Google Scholar : PubMed/NCBI
25	Marotta LL, Almendro V, Marusyk A, Shipitsin M, Schemme J, Walker SR, Bloushtain-Qimron N, Kim JJ, Choudhury SA, Maruyama R, et al: The JAK2/STAT3 signaling pathway is required for growth of CD44(+)CD24(−) stem cell-like breast cancer cells in human tumors. J Clin Invest. 121:2723–2735. 2011. View Article : Google Scholar : PubMed/NCBI
26	Colomiere M, Ward AC, Riley C, Trenerry MK, Cameron-Smith D, Findlay J, Ackland L and Ahmed N: Cross talk of signals between EGFR and IL-6R through JAK2/STAT3 mediate epithelial-mesenchymal transition in ovarian carcinomas. Br J Cancer. 100:134–144. 2009. View Article : Google Scholar : PubMed/NCBI
27	Zhao M, Gao FH, Wang JY, Liu F, Yuan HH, Zhang WY and Jiang B: JAK2/STAT3 signaling pathway activation mediates tumor angiogenesis by upregulation of VEGF and bFGF in non-small-cell lung cancer. Lung Cancer. 73:366–374. 2011. View Article : Google Scholar : PubMed/NCBI
28	Xiong H, Du W, Zhang YJ, Hong J, Su WY, Tang JT, Wang YC, Lu R and Fang JY: Trichostatin A, a histone deacetylase inhibitor, suppresses JAK2/STAT3 signaling via inducing the promoter-associated histone acetylation of SOCS1 and SOCS3 in human colorectal cancer cells. Mol Carcinog. 51:174–184. 2012. View Article : Google Scholar : PubMed/NCBI
29	Kim MJ, Nam HJ, Kim HP, Han SW, Im SA, Kim TY, Oh DY and Bang YJ: OPB-31121, a novel small molecular inhibitor, disrupts the JAK2/STAT3 pathway and exhibits an antitumor activity in gastric cancer cells. Cancer Lett. 335:145–152. 2013. View Article : Google Scholar : PubMed/NCBI
30	Cheng S, Swanson K, Eliaz I, McClintick JN, Sandusky GE and Sliva D: Pachymic acid inhibits growth and induces apoptosis of pancreatic cancer in vitro and in vivo by targeting ER stress. PloS One. 10:e01222702015. View Article : Google Scholar : PubMed/NCBI