Novel insight into mitochondrial dynamin-related protein-1 as a new chemo-sensitizing target in resistant cancer cells

• Published in: Bioorganic chemistry Vol. 150; p. 107574
• Main Authors: Sami Alkafaas, Samar, Obeid, Omar K., Ali Radwan, Mustafa, Elsalahaty, Mohamed I., Samy ElKafas, Sara, Hafez, Wael, Janković, Nenad, Hessien, Mohamed
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2024
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cancer; Chemoresistance; Drp-1; Drug Resistance, Neoplasm - drug effects; Dynamins - antagonists & inhibitors; Dynamins - metabolism; Fission; Humans; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial Dynamics - drug effects; Molecular docking; Molecular Structure; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; Quinazolinones - chemical synthesis; Quinazolinones - chemistry; Quinazolinones - pharmacology; Mitochondria; Drp-1; Fission; Molecular docking; Chemoresistance; Cancer
• ISSN: 0045-2068; 1090-2120; 1090-2120
• DOI: 10.1016/j.bioorg.2024.107574

[Display omitted] Mitochondrial dynamics have pillar roles in several diseases including cancer. Cancer cell survival is monitored by mitochondria which impacts several cellular functions such as cell metabolism, calcium signaling, and ROS production. The equilibrium of death and survival rate of mitochondria is important for healthy cellular processes. Whereas inhibition of mitochondrial metabolism and dynamics can have crucial regulatory decisions between cell survival and death. The steady rate of physiological flux of both mitochondrial fission and fusion is strongly related to the preservation of cellular bioenergetics. Dysregulation of mitochondrial dynamics including fission and fusion is a critical machinery in cells accompanied by crosstalk in cancer progression and resistance. Many cancer cells express high levels of Drp-1 to induce cancer cell invasion, metastasis and chemoresistance including breast cancer, liver cancer, pancreatic cancer, and colon cancer. Targeting Drp-1 by inhibitors such as Midivi-1 helps to enhance the responsiveness of cancer cells towards chemotherapy. The review showed Drp-1 linked processes such as mitochondrial dynamics and relationship with cancer, invasion, and chemoresistance along with computational assessing of all publicly available Drp-1 inhibitors. Drp1-IN-1, Dynole 34–2, trimethyloctadecylammonium bromide, and Schaftoside showed potential inhibitory effects on Drp-1 as compared to standard Mdivi- 1. This emerging approach may have extensive strength in the context of cancer development and chemoresistance and further work is needed to aid in more effective cancer management.