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Oldenlandia diffusa Extracts Exert Anti‐Tumor Effects on Human Ovarian Cancer Cells Via an Epigenetic Regulator, KDM1B
Author(s) -
Lee Yeon Kyu,
Lim Jin Yeong,
Joo Jong Cheon,
Park Soo Jung,
Park Yoon Jung
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb341
Subject(s) - cisplatin , ovarian cancer , viability assay , cancer research , chemistry , carboplatin , cancer , cell , cancer cell , pharmacology , biology , medicine , biochemistry , chemotherapy
Ovarian cancer is the most fatal gynecologic malignancy among women with its high risk of late diagnosis and recurrence. Cisplatin is a platinum‐based anti‐tumor drug, which is widely used against ovarian cancer, however, recurrent tumors after the treatment frequently demonstrate acquired chemo‐resistance. Therefore, identification of alternative treatment for ovarian cancer seems critical. Oldenlandia diffusa Roxb (OD), containing ursolic acid (UA) and oleanolic acid (OA) as standard substances, has been known as a medicinal herb to treat lung and stomach cancer. However, the effect of OD on ovarian cancer is uncertain. This study was aimed to uncover the anti‐tumor effects of OD extracts and/or cisplatin on ovarian cancer cells, in particular carrying cisplatin‐resistance. OD was extracted by two ways using water and 50% methanol. As ovarian cancer cell models, cisplatin sensitive cell A2780 and the counterpart cisplatin resistant cell A2780cis were used. The methanol extract effectively reduced cell viability in both A2780 and A2780cis cells, while the water extract affects significantly cell viability in only A2780 cells, not in A2780cis. The effect of the methanol extract was greater than its standard substances, including UA and OA in both A2780 and A2780cis. Interestingly, combined treatment of cisplatin and the methanol extract substantially reduced cell viability of A2780cis cells, compared to single treatment of either cisplatin or the methanol treatment. Genome wide expression analysis using microarray data revealed that expression of an epigenetic marker lysine demethylase 1B (KDM1B) was upregulated in A2780cis cells compared to A2780 cells, and the result was confirmed by further quantitative analysis. Consistently, treatment of the methanol extract on A2780cis cells significantly reduced KDM1B mRNA expression in a dose‐dependent manner. Moreover, siRNA‐mediated knockdown of KDM1B reduced cell viability of A2780cis under cisplatin treatment, suggesting that KDM1B upregulation in A2780cis, in part, contributes to the cisplatin resistance. The results showed that the OD extract may promote cell death in the resistance cells under cisplatin through modulating KDM1B.