Modulating the p53-MDM2 pathway: the therapeutic potential of natural compounds in cancer treatment

The p53-MDM2 pathway plays a crucial role regulating tumor suppression and is a focal point of cancer research. This literature review delves into the complex interplay between the tumor suppressor protein p53 and its main regulator MDM2, highlighting their interaction and implications in cancer development and progression. The review compiles and summarizes the existing understanding of the biology and regulation of p53 and MDM2, emphasizing their roles in various cellular processes, including cell cycle regulation, DNA repair, apoptosis, and metabolism. It also discusses the disruption of the p53-MDM2 interaction in different cancer types and its impact on tumor progression and therapeutic resistance. Recent studies have highlighted natural products as promising avenues for targeting the p53-MDM2 pathway. This review categorizes these natural compounds into three groups based on their mechanisms: those that inhibit MDM2 expression or stability, those that prevent p53-MDM2 binding, and those that stabilize p53 by inhibiting MDM2's E3 ligase activity. Detailed mechanisms of action, structural aspects, and potential therapeutic applications of various natural products, including polyphenols, terpenoids, and alkaloids, are presented. Despite significant advances in understanding the p53-MDM2 interaction and the identification of natural products capable of modulating this pathway, further research is necessary to evaluate the clinical efficacy, toxicity, and bioavailability of these compounds. The promising role of natural products in cancer therapy underscores the importance of ongoing investigation and development of these agents as potential treatments for cancer.