Rhodomyrtus tomentosa attenuates HER2 expression and modulates apoptotic pathways in DMBA-induced breast carcinogenesis: In vivo and in silico insights

Rhodomyrtus tomentosa , a medicinal plant abundant in polyphenols and indigenous to Indonesia, exhibits significant anticancer potential. This research investigated the effects of Chitosan-formulated extracts of R. tomentosa on HER2 expression and apoptotic signaling pathways, specifically Caspase-3, Fas Ligand, and Cytochrome c , in a rat model of breast cancer induced by 7,12-dimethylbenz [a]anthracene (DMBA). The study employed in-vivo, immunohistochemical, biochemical, and in silico analyses. Phytochemical profiling using LC-HRMS revealed the presence of predominant flavonoids, including myricetin, myricitrin, and quercetin. The compounds demonstrated significant binding affinities to HER2 and apoptotic proteins via molecular docking, with molecular dynamics simulations indicating improved structural stabilization, especially by myricitrin and quercetin. Histological and ELISA evaluations indicated that oral administration of R. tomentosa extract at escalating doses (100, 150, and 200 mg/kg BW) significantly decreased expression levels of HER2, FasL, and Cytochrome c , while also modulating Caspase-3 in both serum and mammary tissues. The maximum dosage (200 mg/kg BW) closely matches the therapeutic efficacy of doxorubicin. The findings indicate that Chitosan-formulated extracts of R. tomentosa reduces breast tumor progression by downregulating HER2 expression and inducing apoptosis through intrinsic and extrinsic pathways. The findings highlight the potential use of R. tomentosa as a bioactive herbal agent in the development of functional food-based adjuvants or complementary therapies for breast cancer treatment. • Rhodomyrtus tomentosa reduces HER2 expression in breast tissue. • In vivo study confirms apoptotic pathway modulation by the plant extract. • LC-HRMS identified myricitrin and quercetin as dominant active compounds. • In silico docking shows strong affinity of flavonoids to HER2 and Caspase-3. • Nanoextract offers potential as plant-based adjuvant for breast cancer therapy.