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Promotion of Cell Death in Cisplatin-Resistant Ovarian Cancer Cells through KDM1B-DCLRE1B Modulation
- Source :
- International Journal of Molecular Sciences, Vol 20, Iss 10, p 2443 (2019), International Journal of Molecular Sciences, Volume 20, Issue 10
- Publication Year :
- 2019
- Publisher :
- MDPI AG, 2019.
-
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.
- Subjects :
- endocrine system diseases
Cell
cisplatin
DCLRE1B
Oldenlandia
lcsh:Chemistry
Medicine
Cytotoxicity
lcsh:QH301-705.5
Spectroscopy
Ovarian Neoplasms
Oldenlandia diffusa
Nuclear Proteins
Combination chemotherapy
Drug Synergism
General Medicine
Computer Science Applications
Gene Expression Regulation, Neoplastic
medicine.anatomical_structure
ovarian cancer
cell death
Female
medicine.drug
Programmed cell death
DNA repair
Cell Survival
Catalysis
Article
Inorganic Chemistry
Downregulation and upregulation
Cell Line, Tumor
Humans
Physical and Theoretical Chemistry
Molecular Biology
Cell Proliferation
Cisplatin
business.industry
Plant Extracts
Organic Chemistry
Oxidoreductases, N-Demethylating
medicine.disease
DNA Repair Enzymes
Exodeoxyribonucleases
KDM1B
lcsh:Biology (General)
lcsh:QD1-999
Drug Resistance, Neoplasm
Cancer research
business
Ovarian cancer
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Volume :
- 20
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....edd34912274eaf7f41d05101bc056416