期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1869, 期 12, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.bbamcr.2022.119344
关键词
Nimbolide; Docetaxel; Prostate cancer; Drug resistance; NF-?B
资金
- Institution of Excellence
- Council of Scientific and Industrial Research
- Indian Science Congress Association (ISCA)
- National Research Foundation of Korea (NRF) - Korean Government (MSIP) [NRF-2021R1I1A2060024, NRF-2022R1I1A1A01071593]
- King Saud University, Riyadh, Saudi Arabia [RSP-2022/383]
This study investigates the combinational effect of docetaxel (DTX) and nimbolide (NL) on advanced prostate cancer. The results show that the co-administration of NL and DTX significantly reduces cell viability and enhances apoptosis in prostate cancer cells. NL also abolishes DTX-induced NF-kappa B activation and expression of antiapoptotic factors. The combination of NL and DTX demonstrates a synergistic antitumor effect and reduces metastases in prostate cancer models.
Prostate cancer is the second most frequent type of cancer that affects men. Docetaxel (DTX) administration is the front-line therapy for patients with advanced prostate cancer and unfortunately, half of these patients develop resistance to DTX which could be due to its ability to activate the NF-kappa B pathway. The combinational effect of DTX and nimbolide on proliferation, apoptosis, activation of NF-kappa B, DNA binding ability of NF-kappa B, and expression of NF-kappa B-targeted gene products was investigated. The antitumor and antimetastatic effect of DTX or NL alone or in combination was also examined. The co-administration of NL and DTX resulted in a significant loss of cell viability with enhanced apoptosis in DTX-sensitive/resistant prostate cancer cells. NL abrogated DTX-triggered NF-kappa B activation and expression of its downstream antiapoptotic factors (survivin, Bcl-2, and XIAP). The combination of NL and DTX significantly reduced the DNA binding ability of NF-kappa B in both cell types. NL significantly enhanced the antitumor effect of DTX and reduced metastases in orthotopic models of prostate cancer. NL abolishes DTX-induced-NF-kappa B activation to counteract cell proliferation, tumor growth, and metas-tasis in the prostate cancer models.
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