Lychee Seed Extract Targets Proliferation, Differentiation, and Cell Cycle Proteins to Suppress Human Colorectal Tumor Growth in Xenograft Models

Colorectal cancer (CRC) remains a leading global health challenge, and natural products are increasingly explored for their multi-targeted therapeutic potential. <i>Litchi chinensis</i> seed extract (LCSE) has shown promising anti-cancer activity in vitro, though its in vivo effects remain underexplored. LCSE was analyzed by colorimetric assays and HPLC to quantify the phytochemical composition. Nude mice bearing HT-29 or SW480 xenografts were orally administered LCSE (0.1 or 0.6 g/kg) daily for 14 days. Tumor volume was measured, and immunohistochemistry was used to assess EGFR, p21, p53, Ki-67, CEA, CK20, CDX2, and Bax expression. Phytochemical profiling demonstrated LCSE contains abundant phenolics and flavonoids, with gallic acid as a predominant constituent, underscoring the potential bioactive properties. LCSE significantly inhibited tumor growth in HT-29 xenografts and dose-dependently reduced EGFR, p21, p53, cell cycle proteins and proliferation/differentiation markers. In SW480 tumors, inhibitory effects were evident primarily at the higher dose, with limited reduction in p53 expression. Bax levels remained unchanged in both models, indicating a non-apoptotic mechanism. No systemic toxicity was observed in treated mice. LCSE exhibits dose-dependent anti-tumor activity in CRC xenografts, likely mediated through suppression of proliferation and modulation of key regulatory proteins rather than apoptosis. These findings support LCSE as a safe, multi-target botanical candidate for CRC intervention and justify further mechanistic and translational studies.