SMAC Mimetic BV6 Co-Treatment Downregulates the Factors Involved in Resistance and Relapse of Cancer: IAPs and Autophagy
Cancer is the utmost common disease-causing death worldwide, characterized by uncontrollable cell division with the potential of metastasis. Overexpression of the Inhibitors of Apoptosis proteins (IAPs) and autophagy correlates with tumorigenesis, therapeutic resistance, and reoccurrence after antic...
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2022-10-01
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| author | Sahar Rafat Prabhakar Singh Kamlesh Kumar Pandey Saleh A. Almatroodi Mohammed A. Alsahli Ahmad Almatroudi Arshad Husain Rahmani Kapil Dev |
| author_facet | Sahar Rafat Prabhakar Singh Kamlesh Kumar Pandey Saleh A. Almatroodi Mohammed A. Alsahli Ahmad Almatroudi Arshad Husain Rahmani Kapil Dev |
| author_sort | Sahar Rafat |
| collection | DOAJ |
| description | Cancer is the utmost common disease-causing death worldwide, characterized by uncontrollable cell division with the potential of metastasis. Overexpression of the Inhibitors of Apoptosis proteins (IAPs) and autophagy correlates with tumorigenesis, therapeutic resistance, and reoccurrence after anticancer therapies. This study illuminates the role and efficacy of smac mimetic compound BV6 alone and in co-treatment with death ligands such as TRAIL and TNFα in the regulation of cell death mechanisms, i.e., apoptosis and autophagy. In this study, MTT assays, wound healing assays, and cellular and nuclear morphological studies were done. DAPI staining, AO/EtBr staining and AnnexinV/PI FACS was done to study the apoptosis. The expression of IAPs and autophagy biomarkers was analyzed using Real time-PCR and western blotting. Meanwhile, TEM demonstrated autophagy and cellular autophagic vacuoles in response to the BV6. The result shows a promising anti-cancer effect of BV6 alone as well as in combinational treatment with TRAIL and TNFα, compared to the lone treatment of TRAIL and TNFα in both breast cancer cell lines. The smac mimetic compound might provide an alternative combinational therapy with conventional anticancer therapies to tackle their inefficiency at the advanced stage of cancer, cancer resistance, and reoccurrence. Also, IAPs and autophagic proteins could act as potent target molecules for the development of novel anti-cancer drugs in pathogenesis and the betterment of regimens for cancer. |
| first_indexed | 2024-03-09T19:15:16Z |
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| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-09T19:15:16Z |
| publishDate | 2022-10-01 |
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| series | Biology |
| spelling | doaj.art-832ca9ca83174aa59ce1eeb4b53760042023-11-24T03:47:46ZengMDPI AGBiology2079-77372022-10-011111158110.3390/biology11111581SMAC Mimetic BV6 Co-Treatment Downregulates the Factors Involved in Resistance and Relapse of Cancer: IAPs and AutophagySahar Rafat0Prabhakar Singh1Kamlesh Kumar Pandey2Saleh A. Almatroodi3Mohammed A. Alsahli4Ahmad Almatroudi5Arshad Husain Rahmani6Kapil Dev7Department of Biotechnology, Jamia Millia Islamia, New Delhi 110025, IndiaDepartment of Anatomy, All India Institute of Medical Sciences, New Delhi 110025, IndiaDepartment of Anatomy, All India Institute of Medical Sciences, New Delhi 110025, IndiaDepartment of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraidah 51452, Saudi ArabiaDepartment of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraidah 51452, Saudi ArabiaDepartment of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraidah 51452, Saudi ArabiaDepartment of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraidah 51452, Saudi ArabiaDepartment of Biotechnology, Jamia Millia Islamia, New Delhi 110025, IndiaCancer is the utmost common disease-causing death worldwide, characterized by uncontrollable cell division with the potential of metastasis. Overexpression of the Inhibitors of Apoptosis proteins (IAPs) and autophagy correlates with tumorigenesis, therapeutic resistance, and reoccurrence after anticancer therapies. This study illuminates the role and efficacy of smac mimetic compound BV6 alone and in co-treatment with death ligands such as TRAIL and TNFα in the regulation of cell death mechanisms, i.e., apoptosis and autophagy. In this study, MTT assays, wound healing assays, and cellular and nuclear morphological studies were done. DAPI staining, AO/EtBr staining and AnnexinV/PI FACS was done to study the apoptosis. The expression of IAPs and autophagy biomarkers was analyzed using Real time-PCR and western blotting. Meanwhile, TEM demonstrated autophagy and cellular autophagic vacuoles in response to the BV6. The result shows a promising anti-cancer effect of BV6 alone as well as in combinational treatment with TRAIL and TNFα, compared to the lone treatment of TRAIL and TNFα in both breast cancer cell lines. The smac mimetic compound might provide an alternative combinational therapy with conventional anticancer therapies to tackle their inefficiency at the advanced stage of cancer, cancer resistance, and reoccurrence. Also, IAPs and autophagic proteins could act as potent target molecules for the development of novel anti-cancer drugs in pathogenesis and the betterment of regimens for cancer.https://www.mdpi.com/2079-7737/11/11/1581autophagyapoptosisIAPssmac mimeticsbreast cancerTRAIL |
| spellingShingle | Sahar Rafat Prabhakar Singh Kamlesh Kumar Pandey Saleh A. Almatroodi Mohammed A. Alsahli Ahmad Almatroudi Arshad Husain Rahmani Kapil Dev SMAC Mimetic BV6 Co-Treatment Downregulates the Factors Involved in Resistance and Relapse of Cancer: IAPs and Autophagy Biology autophagy apoptosis IAPs smac mimetics breast cancer TRAIL |
| title | SMAC Mimetic BV6 Co-Treatment Downregulates the Factors Involved in Resistance and Relapse of Cancer: IAPs and Autophagy |
| title_full | SMAC Mimetic BV6 Co-Treatment Downregulates the Factors Involved in Resistance and Relapse of Cancer: IAPs and Autophagy |
| title_fullStr | SMAC Mimetic BV6 Co-Treatment Downregulates the Factors Involved in Resistance and Relapse of Cancer: IAPs and Autophagy |
| title_full_unstemmed | SMAC Mimetic BV6 Co-Treatment Downregulates the Factors Involved in Resistance and Relapse of Cancer: IAPs and Autophagy |
| title_short | SMAC Mimetic BV6 Co-Treatment Downregulates the Factors Involved in Resistance and Relapse of Cancer: IAPs and Autophagy |
| title_sort | smac mimetic bv6 co treatment downregulates the factors involved in resistance and relapse of cancer iaps and autophagy |
| topic | autophagy apoptosis IAPs smac mimetics breast cancer TRAIL |
| url | https://www.mdpi.com/2079-7737/11/11/1581 |
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