Phytochemical Modulation of the p53 Tumor Suppressor Pathway: Mechanistic Insights, Translational Evidence, and Therapeutic Perspectives in Cancer
Neha Verma, Shubhra Sekhar Chakraborty, Juhikaben Vaibhavkumar Patel, G. Hemalatha, Alok Mukerjee, Bharath Raj K. C., Ramenani Hari Babu, Ankita WalIntroduction:
Cancer is a major global health challenge, with p53 mutations occurring in over 50% of human cancers and contributing to impaired DNA repair and apoptosis. In more recent work, phytochemicals in herbs such as curcumin, resveratrol, genistein, berberine, and withaferin A were found to enhance p53 activity or rescue it in cancer treatment by amplifying the apoptotic effects or tumor-suppressive functions of p53-activated pathways. This review evaluates the effects of curcumin, resveratrol, genistein, berberine, withaferin A, apigenin, betulinic acid, and piperlongumine on the p53 tumor suppressor pathway in cancer, focusing on their ability to restore p53 activity and increase fast apoptosis in cancer cells.
Method:
A comprehensive literature search from 2014 to 2026 was conducted using PubMed, ScienceDirect, and Google Scholar with predefined keywords related to p53, phytochemicals, and cancer. Relevant studies were selected using predefined inclusion and exclusion criteria.
Result:
The reviewed evidence indicates that phytochemicals, including curcumin, resveratrol, berberine, genistein, and withaferin A, enhance p53 signaling, promote apoptosis, and induce G1/S cellcycle arrest, thereby suppressing tumor growth, metastasis, and treatment resistance.
Discussion:
Phytochemicals exert multitarget effects on the p53 pathway but face clinical limitations due to poor bioavailability, pharmacokinetic variability, and tumor heterogeneity. Further clinical studies and advanced drug-delivery systems are needed.
Conclusion:
The use of phytotherapeutic agents targeting the p53 pathway offers a promising, lowtoxicity approach for cancer treatment. They impede malignancy and restore cellular regulation by modulating p53 signaling. Further clinical research, improved bioavailability, and incorporation into current pharmaceuticals are essential for validating phytotherapy as a viable method for cancer treatment.