Quinacrine enhances the efficacy of cisplatin by increasing apoptosis and modulating cancer survival proteins in a colorectal cancer cell line

Abstract

ABSTRACT Background: Cisplatin and platinum-based compounds have been used successfully to treat various cancers. However, their use is often restricted due to the acquired resistance by cancer cells. Over-expression of p53 and inhibition of NF-kB sensitize several cancer cells towards cisplatin-induced apoptosis. Quinacrine, a cytotoxic drug with predictable safety revealed to concurrently suppress NF-kB and activate p53, which may be an attractive adjuvant in cisplatin chemotherapy. Therefore, the objective of the present study was to establish the role of quinacrine as an adjuvant in lowering the dose of cisplatin during cancer therapy to circumvent its toxic effects. Materials and Methods: The colon cancer (HCT-8) cells were cultured and cell survival assays were performed using standard procedures. Cell cycle arrest and the extent of apoptosis were determined using a muse cell analyzer. Cancer survival proteins were analyzed using western blotting techniques. Results and Conclusion: We demonstrated that concomitant use of quinacrine with cisplatin increased cell apoptosis, suppressed cell proliferation and inhibited colony formation in a colorectal cancer cell line. Moreover, cell cycle arrest in the G0/G1 and G2/M phases and upregulation of p53 expression were observed. There was also downregulation of NF-kB and Bcl-xL protein expressions, both of which are associated with enhanced cell apoptosis and an increase in the sensitivity of cancer cells to cisplatin, overcoming its chemoresistance. Overall, the results of the present study and available literature clearly indicate that the use of quinacrine as an adjuvant with cisplatin may enhance its anti-cancer activity and reduce chemoresistance.