Reactive oxygen species mediate thymoquinone-induced apoptosis and activate ERK and JNK signaling

Abstract

Thymoquinone (TQ), a component of black seed essential oil, is known to induce apoptotic cell death and oxidative stress, however, the direct involvement of oxidants in TQ-induced cell death has not been established yet. Here, we show that TQ inhibited the proliferation of a panel of human colon cancer cells (Caco-2, HCT-116, LoVo, DLD-1 and HT-29), without exhibiting cytotoxicity to normal human intestinal FHs74Int cells. Further investigation in DLD-1 revealed that apoptotic cell death is the mechanism for TQ-induced growth inhibition as confirmed by flow cytometry, M30 cytodeath and caspase-3/7 activation. Apoptosis was induced via the generation of reactive oxygen species (ROS) as evidenced by the abrogation of TQ apoptotic effect in cells preincubated with the strong antioxidant N-acetyl cysteine (NAC). TQ increased the phosphorylation states of the mitogen-activated protein kinases (MAPK) JNK and ERK, but not of p38. Their activation was completely abolished in the presence of NAC. Using PD98059 and SP600125, specific ERK and JNK inhibitors, the two kinases were found to possess pro-survival activities in TQ-induced cell death. These data present evidence linking the pro-oxidant effects of TQ with its apoptotic effects in colon cancer and prove a protective role of MAPK.

Cytotoxicity of Nigella Sativa Seed Oil and Extract Against Human Lung Cancer Cell Line

“…The active principles in NSO have been found to exert antineoplastic effects both in vitro and in vivo using various models of carcinogenesis. The active principles of N sativa showed cytotoxicity against number of cancer cells, such as Ehrlich ascites carcinoma, Dalton's lymphoma ascites and Sarcoma-180 cells in a concentration dependent manner (Salomi et al, 1992;El-Najjar et al, 2010). We found that the NSO extracts, even at lower concentrations exhibit the inhibition of A-549 cells, and the cytotoxicity was found more than the NSE extract.…”

Combinatorial effects of thymoquinone on the anti-cancer activity of doxorubicin

“…The p-quinones DOX and TQ can act either as anti-oxidants or pro-oxidants depending on the given redox environment. The anti-proliferative and apoptotic effects of TQ in human colon cancer cells but not in normal intestinal cells were shown by El-Najjar et al to be induced via the generation of ROS [27]. Similary, different apoptosis-triggering mechanisms in normal and tumour cells were established for DOX [23].…”

Gene Expression Study on Similarity Effect of Thymoquinone on Epithelial Breast Cancer and Colorectal Cancer Cell Lines

“…The over expression of CARD16 was validated with RT-qPCR method which was 9.02 up-fold change in breast cancer cell but showed only 1.64 up-fold in colon cancer (Table 5). Previous study on different type of colon cancer reported that Thymoquinone 40 µM concentration cannot lead the cell significantly in the apoptosis process after 24 hours especially in HT-29 cell line [11]. The expression of MTR gene in breast cancer was found to be up-regulated in microarray result by 3.91.…”