Thymoquinone induces G2/M cell cycle phase arrest and apoptosis through inhibition of JNK phosphorylation and induction of p53 and p21 expression in HT-1080 fibrosarcoma cells

Abstract

Abstract Background Resistance to chemotherapy is a major cause of failure in cancer treatment. Several approaches have been used to circumvent this resistance, including the co-treatment with ABC proteins inhibitors. However, such strategy did not significantly improve cancer therapy due to toxicity and bioavailability of these compounds. Antitumor activity of natural compounds has been largely explored during the last decades as an alternative to improve cancer treatment. One of explored natural molecules is thymoquinone which has been demonstrated to inhibit proliferation and to induce apoptosis in different tumor cell lines. Thymoquinone is able to activate several cellular pathways and thereby to affect cell proliferation and survival. Methods: The HT1080 human fibrosarcoma cells has been treated with Thymoquinone and JNK inhibitor SP600125. Results We showed that thymoquinone arrested cell cycle at the G2M phase and induced apoptosis of HT1080 cells. These effects were mediated through the inhibition of JNK phosphorylation and induction of p53 and p21 expression. The use of the JNK inhibitor SP600125 demonstrated that the inhibition of this pathway is involved in the thymoquinone-induced apoptosis and cell cycle arrest. Conclusions Our data clearly showed that thymoquinone, a naturally-occurring compound, induced G2/M cell cycle phase arrest and apoptosis of human fibrosarcoma HT1080 cells via inhibition of JNK phosphorylation and induction of p53 and p21 expression.