Thymoquinone inhibits tumor progression and promotes chemo-sensitivity via modulation of P21/PI3K/Akt axis in colorectal cancer cells

Natural thymoquinone has been extensively used as a chemopreventive agent and has shown potent anticarcinogenic activity against a broad range of human malignancies. However, the underlying mechanisms and involving signaling pathways are still not well studies. Therefore, this study is aimed to evaluate the effects of thymoquinone on the increasing doxorubicin chemosensitivity via targeting P21 and PI3K/AKT signaling. Caco-2 cells were treated with thymoquinone. MTT assay were applied to assess the impact of different dose of thymoquinone on the doxorubicin cytotoxicity. The mRNA and protein expression levels of PI3K, Akt, P21, P53, Cyc D1, Cdk4, Cdk6, PCNA, Bax, Bcl-2 and caspase-3 were assessed by qRT-PCR and western blotting. A cell death ELISA commercial kits were used to measure apoptosis. We found that thymoquinone treatment significantly decreased proliferation rate in Caco-2 colorectal cancer cells. The survival rate of cells was reduced significantly when doxorubicin was combined with thymoquinone. Thymoquinone upregulated p21, P53 and downregulated Cyc D1, Cdk4, Cdk6, PCNA, as well as suppressed PI3K/Akt signaling pathway. We conclude that thymoquinone induces doxorubicin sensitivity in colorectal cancer cells through targeting p21 and the PI3K/AKT pathway, thus implicating its importance in chemotherapy for colorectal cancer.