Abstract
Abstract Objectives Oldenlandia diffusa Rox has been known as a medicinal herb to treat lung and stomach cancer. However, its molecular mechanism has not been fully elucidated. This study was aimed to investigate the anticancer effects of Oldenlandia diffusa extract (EOD) and to identify a target of EOD. Methods EOD was extracted from dried Oldenlandia diffusa with 50% of ethanol, followed by quantification of ursolic acid (UA) and oleanolic acid (OA) as standard substances. To check the cytotoxiticity of EOD, MTT assay was performed for A2780 and A549 cells in various doses. Swiss Target prediction software was used to investigate the activity of UA and OA. cBioPortal and Oncomine Data were analyze for mutational status and RNA expression levels in diverse cancer cells of the candidate target, respectively. TCGA Data from Human Protein Atlas was used to query correlation between expression levels of candidate genes and overall survival times. Results EOD inhibited the growth of the cells in a dose-dependent manner. The 50% inhibitory concentration (IC50) for A2780 cell was 160 μg/mL of EOD for 48hrs and A549 cell viability was decreased to 75% at 800 μg/mL. Swiss Target prediction reports of two pentacyclic triterpene acids, UA and OA, revealed strong interactions with PTP1B in silico tests, which is indirect evidence of capacity. PTP1B mRNA expression was elevated in cancer cell, especially in lung and ovarian cancer. PTP1B amplification or over-expression was significantly associated with poor overall survival of ovarian and lung cancer patients. Conclusions These data suggests that PTP1B might be a direct target of EOD containing high level of ursolic acid to exert anti-cancer property in ovarian and lung cancer. Funding Sources This study was supported by the National Research Foundation of Korea to Y.J.P and S.J.P. DGK is grateful for financial support from Brain Korea Four Project (Education Research Center for 4IR-Based Health Care).
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