Retinoblastoma growth suppression via chebulic acid-mediated apoptosis: A molecular overview of Triphala’s therapeutic promise

Retinoblastoma is the most common intraocular malignancy in children, arising due to mutations in the RB1 gene and dysregulation of apoptotic and proliferative pathways. Conventional management strategies, including chemotherapy, radiotherapy, and enucleation, are often associated with systemic toxicity and long-term complications, necessitating the exploration of safe and effective complementary therapies. Triphala, a classical Ayurvedic formulation comprising Terminalia chebula, Terminalia bellirica, and Emblica officinalis, has been historically recognized for its Rasayana, Chakshushya , and Shothahara properties. Chebulic acid, a principal polyphenolic constituent of Terminalia chebula, has demonstrated potent anticancer effects in preclinical studies. In Y79 retinoblastoma cell lines, chebulic acid induces dose-dependent inhibition of cell proliferation, promotes G1 phase cell-cycle arrest via upregulation of p27, and triggers mitochondrial-mediated apoptosis through disruption of mitochondrial membrane potential, cytochrome c release, and modulation of Bax/Bcl-2 ratios. Furthermore, chebulic acid suppresses nuclear factor kappa B signalling by stabilizing Inhibitor kappa B alpha (IκBα), reducing nuclear translocation of p65, and attenuating pro-survival signalling pathways. These multi-targeted effects directly counteract key oncogenic processes of retinoblastoma, including uncontrolled proliferation, evasion of apoptosis, and RB1 pathway dysregulation. Integration of classical Ayurvedic insights with modern molecular evidence underscores the translational potential of chebulic acid and Triphala as adjuvant therapies in retinoblastoma management. Collectively, this review highlights the mechanistic rationale and therapeutic promise of chebulic acid-mediated apoptosis, advocating further preclinical and clinical investigations to validate efficacy, optimize dosing, and explore combinatorial strategies with conventional treatments.