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Nobiletin Enhances the Chemotherapeutic Efficacy of Docetaxel through Inhibition of Phosphatidylinositol 3-Kinase/Protein Kinase B and Induction of Apoptosis in Colon Cancer Cells

Author(s): C. Li, Chunling Zhang, Yanfei Wang*, Alaa Yousef Ghidan and T. M. Antary
1Department of Anorectal, Affiliated Hospital of Taishan Medical University, 2Department of emergency, Taian City Central Hospital, Taian, Shandong Province 271000, China, 3Department of General Surgery, The Second People Hospital of Dezhou, Dezhou, Shandong Province 253000, China, 4Nanotechnology and Microbiology Research and Development Centre, The Higher Council for Science and Technology, Amman 11941, Jordan, 5Faculty of Agriculture, The University of Jordan, Amman 11942, Jordan

Correspondence Address:
Yanfei Wang, Department of General Surgery, The Second People Hospital of Dezhou, Dezhou, Shandong Province 253000, China, E-mail:

Nobiletin is considered a phyto-flavonoid extracted from citrus peel and shown to several pharmacological roles such as anti-inflammatory, anti-tumor and neuroprotective properties. In this study, we investigate the role of nobiletin combined docetaxel enhances apoptosis in colorectal cancer cell lines. Our results confirmed nobiletin enhanced docetaxel-induced reactive oxygen species generation of human colorectal carcinoma cells and also enhances mitochondrial membrane potential damage in human colorectal carcinoma cells. We have also been noticed that nobiletin improved docetaxel mediated cell death confirmed by dual acridine orange/ethidium bromide assay. Phosphatidylinositol 3-kinase/protein kinase B phosphorylation heavily involved in cancer cell survival and proliferation. In this study, nobiletin inhibits phosphatidylinositol 3-kinase/protein kinase B's phosphorylation when combined with docetaxel treated human colorectal carcinoma cells. Moreover, nobiletin with docetaxel augmented the expression levels of pro-apoptotic genes such as Bax, cytochrome c, caspase 9 and caspase 3 proteins and foremost down regulation of anti-apoptotic gene protein B-cell lymphoma 2. Hence, we confirmed that nobiletin possibly augmenting colon cancer cells compassion to docetaxel chemotherapy and offer a cellular origin for nobiletin’s latent tenders in the chemo sensitization of human colorectal carcinoma cells.

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