Based on these results, we conclude that this novel derivative of sulfonamide (3D) induces 1) ROS-mediated apoptosis; 2) induction of p53 and Bax; 3) inhibition of Bcl2 and BclxL; and 4) cytochrome c release, PARP cleavage and activation of caspases. Our findings further demonstrate that 3D inhibits the JAK2–STAT3 signaling pathway and target genes, which may provide a mechanistic basis for this compound. 3D-mediated inhibition of STAT3 activation also sensitizes Dox efficacy in CRC. Hence, 3D-mediated inhibition of STAT3 activation and induction of ROS-dependent apoptosis suggest that 3D is an attractive candidate for further investigation as a potential anticancer agent.
The authors are grateful to the Deanship of Scientific Research, King Saud University for funding through Vice Deanship of Scientific Research Chairs.
The authors report no conflicts of interest in this work.
Omar Al-Obeed,1 Mansoor-Ali Vaali-Mohammed,1 Wagdy M. Eldehna,2 Khayal Al-Khayal,1 Amer Mahmood,3 Hatem A. Abdel-Aziz,4 Ahmed Zubaidi,1 Ahmed Alafeefy,5 Maha Abdulla,1 Rehan Ahmad1
1Colorectal Research Chair, Department of Surgery, King Khaled University Hospital, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt; 3Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 4Department of Applied Organic Chemistry, National Research Center, Cairo, Egypt; 5Department of Chemistry, Kulliyyah of Science, International Islamic University, Kuantan, Malaysia
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Source: OncoTargets and Therapy
Originally published June 5, 2018.