Inhibition of Autophagy and the Cytoprotective Role of Smac Mimetic against ROS-Induced Cancer: A Potential Therapeutic Strategy in Relapse and Chemoresistance Cases in Breast Cancer

Author:

Rafat Sahar1,Hakami Mohammed Ageeli2ORCID,Hazazi Ali3,Alsaiari Ahad Amer4ORCID,Rashid Summya5,Hasan Mohammad Raghibul2ORCID,Aloliqi Abdulaziz A.6ORCID,Eisa Alaa Abdulaziz7,Dar Mohammad Irfan1,Khan Mohd Faisal1,Dev Kapil1

Affiliation:

1. Department of Biotechnology, Jamia Millia Islamia, New Delhi 110025, India

2. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Al-Quwayiyah, Riyadh 11911, Saudi Arabia

3. Department of Pathology and Laboratory Medicine, Security Forces Hospital Program, Riyadh 11481, Saudi Arabia

4. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif 21944, Saudi Arabia

5. Department of Pharmacology & Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia

6. Department of Medical Biotechnology, College of Applied Medical Sciences, Qassim University, Buraydah 51542, Saudi Arabia

7. Department of Medical Laboratories Technology, College of Applied Medical Sciences, Taibah University, Medina 42353, Saudi Arabia

Abstract

With more than a million deaths each year, breast cancer is the top cause of death in women. Around 70% of breast cancers are hormonally responsive. Although several therapeutic options exist, cancer resistance and recurrence render them inefficient and insufficient. The major key reason behind this is the failure in the regulation of the cell death mechanism. In addition, ROS was also found to play a major role in this problem. The therapeutic benefits of Smac mimetic compound (SMC) BV6 on MCF7 were examined in the current study. Treatment with BV6 reduces viability and induces apoptosis in MCF7 breast cancer cells. BV6 suppresses autophagy and has demonstrated a defensive role in cancer cells against oxidative stress caused by H2O2. Overall, the present investigation shows that SMC has therapeutic and cytoprotective potential against oxidative stress in cancer cells. These Smac mimetic compounds may be used as anti-cancer drugs as well as antioxidants alone or in conjunction with other commonly used antioxidants.

Funder

DST-SERB: Department of Science and Technology, Government of India

Publisher

MDPI AG

Subject

Microbiology (medical),Molecular Biology,General Medicine,Microbiology

Reference42 articles.

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3. Endocrine resistance associated with activated ErbB system in breast cancer cells is reversed by inhibiting MAPK or PI3K/Akt signaling pathways;Ghayad;Int. J. Cancer,2010

4. MCF-7 Cells—Changing the Course of Breast Cancer Research and Care for 45 Years;Lee;JNCI J. Natl. Cancer Inst.,2015

5. Apoptosis, Chemoresistance, and Breast Cancer: Insights from the MCF-7 Cell Model System;Simstein;Exp. Biol. Med.,2003

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