Cytotoxicity of thymoquinone alone or in combination with cisplatin (CDDP) against oral squamous cell carcinoma in vitro

Abstract

Cisplatin (CDDP) is potent anticancer agent used for several tumor types. Thymoquinone (TQ) is naturally occurring compound drawing great attention as anticancer and chemomodulator for chemotherapies. Herein, we studied the potential cytotoxicity of thymoquinone, CDDP and their combination against human oral squamous cell carcinoma cell in contrast to normal oral epithelial cells. CDDP similarly killed both head and neck squamous cell carcinoma cells (UMSCC-14C) and normal oral epithelial cells (OEC). TQ alone exerted considerable cytotoxicity against UMSCC-14C cells; while it induced weaker killing effect against normal oral epithelial cells (OEC). Equitoxic combination of TQ and CDDP showed additive to synergistic interaction against both UMSCC-14C and OEC cells. TQ alone increased apoptotic cell fraction in UMSCC-14C cells, as early as after 6 hours. In addition, prolonged exposure of UMSCC-14C to TQ alone resulted in 96.7 ± 1.6% total apoptosis which was increased after combination with CDDP to 99.3 ± 1.2% in UMSCC-14C cells. On the other hand, TQ induced marginal increase in the apoptosis in OEC and even decreased the apoptosis induced by CDDP alone. Finally, apoptosis induction results were confirmed by the change in the expression levels of p53, Bcl-2 and Caspase-9 proteins in both UMSCC-14c and OEC cells.

Chemopreventive and Anticancer Effects of Thymoquinone: Cellular and Molecular Targets

“…Anti-oxidant activity of TQ has also been attributed to its inhibitory effect on diethylnitrosamine-induced hepatic carcinogenesis through a similar upregulation of anti-oxidant enzyme levels [49]. In addition, the anti-oxidant effect of TQ is also associated with the ability of TQ to suppress the adverse effects of chemotherapeutic agents such as cyclophosphamide [52], cisplatin [53,54], and doxorubicin [55] in non-cancerous cells and tissues [26]. Thus, TQ-mediated increase in the levels of anti-oxidant enzyme plays a significant role in the oxidative stress-induced tumorigenesis and chemically induced carcinogenesis as well as the cytoprotection against chemotherapeutic toxicity [56].…”

“…TQ has been shown to antagonize the therapeutic efficacy of paclitaxel in breast cancer cell lines [163]. It is also of importance to note that although TQ-cisplatin combination treatment showed synergy in an in vitro oral squamous cell carcinoma model, it contrarily increased cytotoxicity to normal oral epithelial cells [54]. In a similar vein, a recent in vivo study, while emphasizing the potency of TQ in combination therapy with cisplatin in ovarian cancer xenograft tumor growth [151], gives cautions that the long-term treatment with TQ leads to an increase in the NF-κB activity and attenuation of its therapeutic efficacy [164].…”

Trichosanthes kirilowii lectin alleviates diabetic nephropathy by inhibiting the LOX1/NF-κB/caspase-9 signaling pathway

“…Caspase-9 is a key molecule involved in apoptosis [ 29 ]. To understand whether TKL’s ability to protect against the toxic effects of high-glucose treatment was related to caspase-9, we performed immunofluoresence assays to examine the relative levels of caspase-9 expression in HG-treated HK-2 cells with or without different concentrations of TKL ( Figure 3 B).…”

Antibacterial and Antibiofilm Activity of Temporin-GHc and Temporin-GHd Against Cariogenic Bacteria, Streptococcus mutans

“…Human oral epithelial cells (HOECs) were purchased from Shrdio Company (Nanjing, China). The cytotoxicity of GHc or GHd on HOECs was evaluated by a Cell Counting Kit-8 (CCK-8) assay (Beyotime Biotechnology, China) (Alaufi et al, 2017;Liu et al, 2017). HOECs were grown in Dulbecco's modified Eagle's medium (DMEM) containing 10% fatal bovine serum (FBS) and cultured in a humidified atmosphere of 5% CO 2 at 37°C.…”