Promotion of Cell Death in Cisplatin-Resistant Ovarian Cancer Cells through KDM1B-DCLRE1B Modulation

被引:20
作者
Lee, Yeon Kyu [1 ]
Lim, Jinyeong [1 ]
Yoon, So Young [1 ]
Joo, Jong Cheon [2 ]
Park, Soo Jung [3 ]
Park, Yoon Jung [1 ]
机构
[1] Ewha Womans Univ, Dept Nutr Sci & Food Management, Seoul 03760, South Korea
[2] Wonkwang Univ, Coll Korean Med, Dept Sasang Constitut Med, Iksan 54538, South Korea
[3] Woosuk Univ, Coll Korean Med, Dept Sasang Constitut Med, Jeonju 55338, South Korea
基金
新加坡国家研究基金会;
关键词
ovarian cancer; Oldenlandia diffusa; cisplatin; cell death; KDM1B; DCLRE1B; OLDENLANDIA-DIFFUSA; DEMETHYLASE; APOPTOSIS; RESPONSES; REPAIR; AGENTS;
D O I
10.3390/ijms20102443
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Ovarian cancer is the gynecological malignancy with the poorest prognosis, in part due to its high incidence of recurrence. Platinum agents are widely used as a first-line treatment against ovarian cancer. Recurrent tumors, however, frequently demonstrate acquired chemo-resistance to platinum agent toxicity. To improve chemo-sensitivity, combination chemotherapy regimens have been investigated. This study examined anti-tumor effects and molecular mechanisms of cytotoxicity of Oldenlandia diffusa (OD) extracts on ovarian cancer cells, in particular, cells resistant to cisplatin. Six ovarian cancer cells including A2780 and cisplatin-resistant A2780 (A2780cis) as representative cell models were used. OD was extracted with water (WOD) or 50% methanol (MOD). MOD significantly induced cell death in both cisplatin-sensitive cells and cisplatin-resistant cells. The combination treatment of MOD with cisplatin reduced viability in A2780cis cells more effectively than treatment with cisplatin alone. MOD in A2780cis cells resulted in downregulation of the epigenetic modulator KDM1B and the DNA repair gene DCLRE1B. Transcriptional suppression of KDM1B and DCLRE1B induced cisplatin sensitivity. Knockdown of KDM1B led to downregulation of DCLRE1B expression, suggesting that DCLRE1B was a KDM1B downstream target. Taken together, OD extract effectively promoted cell death in cisplatin-resistant ovarian cancer cells under cisplatin treatment through modulating KDM1B and DCLRE1B.
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页数:13
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