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

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.

KDM1A Identified as a Potential Oncogenic Driver and Prognostic Biomarker via Multi-Omics Analysis

“…KDM1B/AOF1, as another member of the KDM1s family, is a histone H3K4 demethylase [32]. KDM1B plays different roles in the regulation of proliferation, apoptosis, and stemness in several cancers, such as breast cancer, ovarian cancer, and pancreatic cancer [24,[33][34][35]. In this study, we used pan-cancer analysis to systematically characterize the roles of KDM1A.…”

Pd-catalyzed Suzuki–Miyaura couplings and evaluation of 13α-estrone derivatives as potential anticancer agents

“…These two types of HPV are responsible for nearly 70% of cervical cancerous cases. Ovarian cancer is another common type of gynecological malignancies [38]. Its poor prognosis and high mortality rates arise from its high recurrence and acquired resistance to drug treatment.…”

Transition metal-catalysed A-ring C–H activations and C(sp2)–C(sp2) couplings in the 13α-oestrone series and in vitro evaluation of antiproliferative properties

“…The antiproliferative properties of the newly synthesised compounds (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) and their parent derivatives 11 or 12 were investigated in vitro on a panel of human adherent cancer cell lines representing the most relevant cancers of gynaecological origin. The panel included different breast (MCF-7 and MDA-MB-231), cervical (HeLa and SiHa), and ovarian (A2780 40,41 ) cancer cell lines. While MCF-7 is an oestrogen receptor positive cell line, MDA-MB-231 is lacking receptors for oestrogens, progesterone, and HER2 growth factor [41][42][43][44] .…”