Promotion of cell death in cisplatin-resistant ovarian cancer cells through KDM1B-DCLRE1B modulation

Yeon Kyu Lee, Jinyeong Lim, So Young Yoon, Jong Cheon Joo, Soo Jung Park, Yoon Jung Park

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17 Scopus citations


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.

Original languageEnglish
Article number2443
JournalInternational Journal of Molecular Sciences
Issue number10
StatePublished - 2 May 2019

Bibliographical note

Funding Information:
Funding: This research was funded Basic Science Research Programs through the National Research Foundation (NRF) of Korea funded by the Korea government (2018R1D1A1B07051274 to YJP and 2017R1D1A1B03034936 to SJP). Y.K.L., J.L., and S.Y.Y. were supported by Brain Korea 21 plus project (22A20130012143).

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.


  • Cell death
  • Cisplatin
  • KDM1B
  • Oldenlandia diffusa
  • Ovarian cancer


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