Salvianolic acid A positively regulates PTEN protein level and inhibits growth of A549 lung cancer cells

Bi,Lei; Chen,Jianping; Yuan,Xiaojing; Jiang,Zequn; Chen,Weiping

doi:10.3892/br.2012.33

Salvianolic acid A positively regulates PTEN protein level and inhibits growth of A549 lung cancer cells

Authors:
- Lei Bi
- Jianping Chen
- Xiaojing Yuan
- Zequn Jiang
- Weiping Chen
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Affiliations: The Associated Hospital of Nanjing University of Chinese Medicine, Nanjing 210046, P.R. China, College of Basic Medicine, Nanjing University of Chinese Medicine, Nanjing 210046, P.R. China
Published online on: October 29, 2012 https://doi.org/10.3892/br.2012.33
Pages: 213-217

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Abstract

Salvianolic acid A (Sal A) is an effective compound extracted from Salvia miltiorrhiza which has been used in the treatment of various diseases. Preliminary data indicate that Sal A treatment has a specific anti‑lung cancer effect. However, the manner in which Sal A regulates cancer growth remains unknown. In this study, the A549 lung cancer cell line and its response to Sal A treatment was examined. Results showed that Sal A treatment significantly decreased A549 cell growth, promoted partial apoptosis and increased mitochondrial membrane permeability. Western blot analysis showed that Sal A upregulated the phosphatase and tensin homolog (PTEN) protein level, while consistently downregulating Akt phosphorylation. These results indicate that Sal A negatively mediates A549 lung cancer cell line growth or apoptosis, most likely by positively regulating PTEN protein level.

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1	Li Z, Zhang W, Zhao Y, et al: Research progress of salvianolic acid A. Zhongguo Zhong Yao Za Zhi. 36:2603–2609. 2011.(In Chinese).
2	Zhang W and Lu Y: Advances in studies on antitumor activities of compounds in Salvia miltiorrhiza. Zhongguo Zhong Yao Za Zhi. 35:389–392. 2010.(In Chinese).
3	Zhang S, Su J and Zhen Y: Salvianolic acid A inhibits nucleoside transport and potentiates the antitumor activity of chemotherapeutic drugs. Yao Xue Xue Bao. 39:496–499. 2004.(In Chinese).
4	Osaki M, Oshimura M and Ito H: PI3K-Akt pathway: its functions and alterations in human cancer. Apoptosis. 9:667–676. 2004. View Article : Google Scholar : PubMed/NCBI
5	Nielsen-Preiss SM, Silva SR and Gillette JM: Role of PTEN and Akt in the regulation of growth and apoptosis in human osteoblastic cells. J Cell Biochem. 90:964–975. 2003. View Article : Google Scholar : PubMed/NCBI
6	Koseoglu S, Lu Z, Kumar C, Kirschmeier P and Zou J: AKT1, AKT2 and AKT3-dependent cell survival is cell line-specific and knockdown of all three isoforms selectively induces apoptosis in 20 human tumor cell lines. Cancer Biol Ther. 6:755–762. 2007. View Article : Google Scholar : PubMed/NCBI
7	Shinji K, Sasazawa Y, Imamichi Y, et al: Caffeine induces apoptosis by enhancement of autophagy via PI3K/Akt/mTOR/p70S6K inhibition. Autophagy. 7:176–187. 2011. View Article : Google Scholar : PubMed/NCBI
8	Huang WC and Hung MC: Induction of Akt activity by chemotherapy confers acquired resistance. J Formos Med Assoc. 108:180–194. 2009. View Article : Google Scholar : PubMed/NCBI
9	Leslie NR and Downes CP: PTEN function: how normal cells control it and tumour cells lose it. Biochem J. 382:1–11. 2004. View Article : Google Scholar : PubMed/NCBI
10	Chu EC and Tarnawski AS: PTEN regulatory functions in tumor suppression and cell biology. Med Sci Monit. 10:RA235–RA241. 2004.PubMed/NCBI
11	Lee JO, Yang H, Georgescu MM, et al: Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association. Cell. 99:323–334. 1999. View Article : Google Scholar : PubMed/NCBI
12	Denley A, Gymnopoulos M, Kang S, et al: Requirement of phosphatidylinositol (3,4,5) trisphosphate in phosphatidylinositol 3-kinase-induced oncogenic transformation. Mol Cancer Res. 7:1132–1138. 2009. View Article : Google Scholar : PubMed/NCBI
13	Degtyarev M, De Mazière A, Orr C, et al: Akt inhibition promotes autophagy and sensitizes PTEN-null tumors to lysosomotropic agents. J Cell Biol. 183:101–116. 2008. View Article : Google Scholar : PubMed/NCBI
14	Carnero A, Blanco-Aparicio C, Renner O, et al: The PTEN/PI3K/AKT signaling pathway in cancer, therapeutic implications. Curr Cancer Drug Targets. 8:187–198. 2008. View Article : Google Scholar : PubMed/NCBI
15	Pappas G, Zumstein LA, Munshi A, et al: Adenoviral-mediated PTEN expression radiosensitizes non-small cell lung cancer cells by suppressing DNA repair capacity. Cancer Gene Ther. 14:543–549. 2007. View Article : Google Scholar : PubMed/NCBI
16	Kappes H, Goemann C, Bamberger AM, et al: PTEN expression in breast and endometrial cancer: correlations with steroid hormone receptor status. Pathobiology. 69:136–142. 2001. View Article : Google Scholar : PubMed/NCBI