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Article

Induction of ROS‑mediated cell death and activation of the JNK pathway by a sulfonamide derivative

  • Authors:
    • Rehan Ahmad
    • Mansoor‑Ali Vaali‑Mohammed
    • Mohammed Elwatidy
    • Omar Al‑Obeed
    • Khayal Al‑Khayal
    • Wagdy M. Eldehna
    • Hatem A. Abdel‑Aziz
    • Ahmed Alafeefy
    • Maha Abdulla
  • View Affiliations / Copyright

    Affiliations: Colorectal Research Chair, Department of Surgery, King Khaled University Hospital, College of Medicine, King Saud University, Riyadh 11472, Saudi Arabia, CMRC, College of Medicine, King Saud University, Riyadh 11472, Saudi Arabia, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33511, Egypt, Department of Applied Organic Chemistry, National Research Center, Cairo 12622, Egypt, Department of Chemistry, Kulliyyah of Science, International Islamic University, Kuantan 25200, Malaysia
  • Pages: 1552-1562
    |
    Published online on: July 23, 2019
       https://doi.org/10.3892/ijmm.2019.4284
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Abstract

The emergence of colorectal cancer in developed nations can be attributed to dietary habits, smoking, a sedentary lifestyle and obesity. Several treatment regimens are available for primary and metastatic colorectal cancer; however, these treatment options have had limited impact on cure and disease‑free survival, and novel agents need to be developed for treating colorectal cancer. Thus, the objective of this study was to explore the anticancer mechanism of a benzo(1,3)dioxol‑based derivative of sulfonamide. The compound's inhibitory effect on cell proliferation was determined using the MTT assay and the xCelligence RTDP machine. Alternations in the expression of Bcl‑2 and inhibitor of apoptosis protein families were detected by western blotting. Apoptotic marker protein expression, including cytochrome c and cleaved poly(ADP‑ribose)polymerase was measured in the cytosolic extract of cells. Apoptosis and necrosis were detected by flow cytometry and immunofluorescence. Reactive oxygen species (ROS), and activation of caspase‑3 and caspase‑7 were measured using flow cytometry. Activation of the JNK pathway was detected by western blotting. We investigated the molecular mechanism of action of the sulfonamide derivative on colorectal cancer cells and found that the compound possesses a potent anticancer effect, which is primarily exerted by inducing apoptosis and necrosis. Interestingly, this compound exhibited little antiproliferative effect against the normal colonic epithelial cell line FHC. Furthermore, our results showed that the compound could significantly increase ROS production. Apoptosis induction could be attenuated by the free oxygen radical scavenger N‑acetyl cysteine (NAC), indicating that the antiproliferative effect of this compound on colorectal cancer cells is at least partially dependent on the redox balance. In addition, JNK signaling was activated by treatment with this derivative, which led to the induction of apoptosis. On the contrary, a JNK inhibitor could suppress the cell death induced by this compound. Our findings thus suggested a novel anticancer mechanism of a benzo(1,3)dioxol‑based derivative of sulfonamide for colorectal cancer cells and may have therapeutic potential for the treatment of colorectal cancer; however, further investigation is required.
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Copy and paste a formatted citation
Spandidos Publications style
Ahmad R, Vaali‑Mohammed MA, Elwatidy M, Al‑Obeed O, Al‑Khayal K, Eldehna WM, Abdel‑Aziz HA, Alafeefy A and Abdulla M: Induction of ROS‑mediated cell death and activation of the JNK pathway by a sulfonamide derivative. Int J Mol Med 44: 1552-1562, 2019.
APA
Ahmad, R., Vaali‑Mohammed, M., Elwatidy, M., Al‑Obeed, O., Al‑Khayal, K., Eldehna, W.M. ... Abdulla, M. (2019). Induction of ROS‑mediated cell death and activation of the JNK pathway by a sulfonamide derivative. International Journal of Molecular Medicine, 44, 1552-1562. https://doi.org/10.3892/ijmm.2019.4284
MLA
Ahmad, R., Vaali‑Mohammed, M., Elwatidy, M., Al‑Obeed, O., Al‑Khayal, K., Eldehna, W. M., Abdel‑Aziz, H. A., Alafeefy, A., Abdulla, M."Induction of ROS‑mediated cell death and activation of the JNK pathway by a sulfonamide derivative". International Journal of Molecular Medicine 44.4 (2019): 1552-1562.
Chicago
Ahmad, R., Vaali‑Mohammed, M., Elwatidy, M., Al‑Obeed, O., Al‑Khayal, K., Eldehna, W. M., Abdel‑Aziz, H. A., Alafeefy, A., Abdulla, M."Induction of ROS‑mediated cell death and activation of the JNK pathway by a sulfonamide derivative". International Journal of Molecular Medicine 44, no. 4 (2019): 1552-1562. https://doi.org/10.3892/ijmm.2019.4284
Copy and paste a formatted citation
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Spandidos Publications style
Ahmad R, Vaali‑Mohammed MA, Elwatidy M, Al‑Obeed O, Al‑Khayal K, Eldehna WM, Abdel‑Aziz HA, Alafeefy A and Abdulla M: Induction of ROS‑mediated cell death and activation of the JNK pathway by a sulfonamide derivative. Int J Mol Med 44: 1552-1562, 2019.
APA
Ahmad, R., Vaali‑Mohammed, M., Elwatidy, M., Al‑Obeed, O., Al‑Khayal, K., Eldehna, W.M. ... Abdulla, M. (2019). Induction of ROS‑mediated cell death and activation of the JNK pathway by a sulfonamide derivative. International Journal of Molecular Medicine, 44, 1552-1562. https://doi.org/10.3892/ijmm.2019.4284
MLA
Ahmad, R., Vaali‑Mohammed, M., Elwatidy, M., Al‑Obeed, O., Al‑Khayal, K., Eldehna, W. M., Abdel‑Aziz, H. A., Alafeefy, A., Abdulla, M."Induction of ROS‑mediated cell death and activation of the JNK pathway by a sulfonamide derivative". International Journal of Molecular Medicine 44.4 (2019): 1552-1562.
Chicago
Ahmad, R., Vaali‑Mohammed, M., Elwatidy, M., Al‑Obeed, O., Al‑Khayal, K., Eldehna, W. M., Abdel‑Aziz, H. A., Alafeefy, A., Abdulla, M."Induction of ROS‑mediated cell death and activation of the JNK pathway by a sulfonamide derivative". International Journal of Molecular Medicine 44, no. 4 (2019): 1552-1562. https://doi.org/10.3892/ijmm.2019.4284
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