Salinity-induced capsaicin biosynthesis in Capsicum annuum L.: mechanistic and molecular insights into its potential role in prostate adenocarcinoma.

Prostate cancer incidence is expected to double by 2040, with related deaths rising by 80% highlighting the urgent need for effective prevention and treatment strategies. This growing concern has increased interest in utilising natural plant compounds for cancer therapies. Capsaicin, a key component of Capsicum annuum L., is well renowned for its anti-cancerous properties. Results of quantitative UHPLC-HRMS analysis revealed that capsaicin accumulation was significantly increased in fruits of Capsicum annum L. treated with 50 and 100 mM salinity compared to control (0 mM). These findings suggest that salinity stress enhanced anti-cancer potential of Capsicum annuum L. while presenting a sustainable solution for utilizing salinity-affected lands to enhance capsaicin production. To elucidate capsaicin mechanism against prostate adenocarcinoma, five hub targets were identified through network pharmacology and protein-protein interaction network analysis. KEGG pathway analysis revealed four key targets (ERBB2, HSP90AA1, MTOR, and PIK3CA) involved in tumour growth, cell proliferation, and survival via the PI3K-Akt, MAPK, and androgen receptor pathways. Gene (GEPIA2) and protein expression analysis (Human Protein Atlas) confirmed their overexpression in prostate adenocarcinoma cells, underscoring their therapeutic relevance. Docking studies along with molecular dynamic simulations further demonstrated significant binding affinities between capsaicin and these targets (ERBB2: - 6.207; HSP90AA1: - 4.846; MTOR: - 6.451 and PIK3CA: - 6.720 Kcal/mol) suggest that capsaicin may disrupt the PI3K/Akt/mTOR and MAPK signaling pathways, potentially leading to the suppression of prostate cancer. Our Insilco based findings suggest that capsaicin interacts with key molecular targets associated with prostate cancer pathways, further in vivo validations are necessary to confirm its therapeutic potential.