Enhancement of Cisplatin Cytotoxicity in Combination with Thymoquinone on Oral Cancer HSC-4 Cell Line

Abstract

Cisplatin (CDDP) is frequently used as an adjuvant chemotherapy in oral cancer management and often associated with significant adverse effects. Natural occurring compounds have provided considerable value in cancer chemotherapeutic research. Thymoquinone (TQ), the main constituent of Nigella sativa has been widely known for its anti-neoplastic activities with negligible undesirable effect on normal cells. The purpose of this study was to investigate the enhancement of CDDP cytotoxicity in combination with TQ oral cancer HSC-4 cell line. Cytotoxicity assay followed by Isobologram and Combination Index (CI) analysis using CompuSyn software demonstrated that combined exposure of 1.66 μM (‘low-dose’) of CDDP and 1.52 μM of TQ exhibited synergism on HSC-4 cells with CI value <1 (0.362 and 0.538 at 24h and 48h, respectively). In addition, it was revealed that the low CDDP dose used in the assay was sufficient to reduce the percentage of viable HSC-4 cells at the level comparable to those exposed to IC50 dose of CDDP alone (16.9 μM and 1.97 μM at 24h and 48h respectively). The cytotoxicity assay also confirmed that CDDP treatment at the low-dose had no effect on human oral fibroblasts viability. The study indicates the potential use of TQ to augment the chemotherapeutic activities of CDDP against oral cancers while minimizing the CDDP toxic side effects on normal cells.