HO-3867, a curcumin analog, sensitizes cisplatin-resistant ovarian carcinoma, leading to therapeutic synergy through STAT3 inhibition

• DOI: 10.4161/cbt.12.9.17713
• Publication Date: 2011-11-01T14:05:45Z
• Authors: Karuppaiyah Selve...; Shabnam Ahmed; Alex Dayton; M. Lakshmi Kuppusamy; Brian K. Rivera; Tamás Kálai; Kálmán Hideg; Periannan Kuppusamy
• Keywords: RM Therapeutics. Pharmacology / terápia; STAT3 Transcription Factor; 0301 basic medicine; Curcumin; Mice, Nude; Antineoplastic Agents; Apoptosis; Cell Cycle Proteins; Mice; 03 medical and health sciences; Cell Line, Tumor; Animals; Humans; Piperidones; Cell Proliferation; Ovarian Neoplasms; Mice, Inbred BALB C; Cell Cycle; Drug Synergism; 3. Good health; gyógyszertan; Drug Resistance, Neoplasm; Female; Cisplatin; Apoptosis Regulatory Proteins

Cisplatin resistance is a major obstacle in the treatment of ovarian cancer. Drug combinations with synergistic or complementary functions are promising strategy to overcome this issue. We studied anticancer efficacy novel compound, HO-3867, used combination cisplatin against chemotherapy-resistant A2780R cells, cisplatin-resistant human cancer cell line, were exposed 1, 5, 10 uM HO-3867 alone (10 ug/ml) for 24 hours. Cell viability (MTT), proliferation (BrdU), cell-cycle analysis (FACS), and protein expression (western blot) vitro studies. STAT3 overexpression was performed using transfected cDNA. In vivo studies xenograft tumors grown nude mice treated 100-ppm weekly injections 4-mg/kg cisplatin. HO-3867/cisplatin significantly inhibited concentration-dependent manner. The inhibition associated increased p53 p21, decreased cdk5 cyclin D1. Apoptosis induced by activation Bax, cytochrome c release, stimulated cleavage caspase-9, caspase-3, PARP. Overexpression HO-3867-induced apoptosis. growth significant downregulation pSTAT3, without apparent toxicity healthy tissues. exhibited efficacy, which appears largely due pSTAT3. results, combined previously-reported safety features suggest potential use compound as safe effective adjuvant