p53 Modulation of Autophagy Signaling in Cancer Therapies: Perspectives Mechanism and Therapeutic Targets

Frontiers in Cell and Developmental Biology

Md Jamal Uddin³  Md Mamunur Rashid³  MD Hasanur Rahman⁵  Rokibul Islam⁶  Moon Nyeo Park⁸  Bonglee Kim⁸  Md Ataur Rahman⁹  Md Abdul Hannan^1,10 

[1] Biomedical Research Network (GBBRN), Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia, Bangladesh;0Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University, Mymensingh, Bangladesh;ABEx Bio-Research Center, Dhaka, Bangladesh;Department of Biochemistry, College of Medicine, Hallym University, Chuncheon, South Korea;Department of Biotechnology and Genetic Engineering, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Bangladesh;Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia, Bangladesh;Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, United States;Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, South Korea;;Global Biotechnology &Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, Korea;Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul, South Korea;

关键词: p53;    autophagy;    apoptosis;    tumor suppressor;    synthetic drug;    phytochemical;   

DOI  :  10.3389/fcell.2022.761080

来源: DOAJ

【 摘 要 】

The key tumor suppressor protein p53, additionally known as p53, represents an attractive target for the development and management of anti-cancer therapies. p53 has been implicated as a tumor suppressor protein that has multiple aspects of biological function comprising energy metabolism, cell cycle arrest, apoptosis, growth and differentiation, senescence, oxidative stress, angiogenesis, and cancer biology. Autophagy, a cellular self-defense system, is an evolutionarily conserved catabolic process involved in various physiological processes that maintain cellular homeostasis. Numerous studies have found that p53 modulates autophagy, although the relationship between p53 and autophagy is relatively complex and not well understood. Recently, several experimental studies have been reported that p53 can act both an inhibitor and an activator of autophagy which depend on its cellular localization as well as its mode of action. Emerging evidences have been suggested that the dual role of p53 which suppresses and stimulates autophagy in various cencer cells. It has been found that p53 suppression and activation are important to modulate autophagy for tumor promotion and cancer treatment. On the other hand, activation of autophagy by p53 has been recommended as a protective function of p53. Therefore, elucidation of the new functions of p53 and autophagy could contribute to the development of novel therapeutic approaches in cancer biology. However, the underlying molecular mechanisms of p53 and autophagy shows reciprocal functional interaction that is a major importance for cancer treatment and manegement. Additionally, several synthetic drugs and phytochemicals have been targeted to modulate p53 signaling via regulation of autophagy pathway in cancer cells. This review emphasizes the current perspectives and the role of p53 as the main regulator of autophagy-mediated novel therapeutic approaches against cancer treatment and managements.

【 授权许可】

Unknown