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

Title
Promotion of Cell Death in Cisplatin-Resistant Ovarian Cancer Cells through KDM1B-DCLRE1B Modulation
Authors
Lee, Yeon KyuLim, JinyeongYoon, So YoungJoo, Jong CheonPark, Soo JungPark, Yoon Jung
Ewha Authors
박윤정
SCOPUS Author ID
박윤정scopus
Issue Date
2019
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN
1422-0067JCR Link
Citation
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES vol. 20, no. 10
Keywords
ovarian cancerOldenlandia diffusacisplatincell deathKDM1BDCLRE1B
Publisher
MDPI
Indexed
SCIE; SCOPUS WOS
Document Type
Article
Abstract
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.
DOI
10.3390/ijms20102443
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신산업융합대학 > 식품영양학과 > Journal papers
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