Dendrobium officinale inhibits colorectal cancer progression by induction of glutathione peroxidase 4-mediated ferroptosis

Colorectal cancer (CRC), one of the leading causes of cancer-related mortality globally, urgently requires complementary and alternative therapies. Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation, has emerged as a promising anticancer modality. Dendrobium officinale (D. officinale), a renowned traditional Chinese medicinal herb, has been extensively utilized across various Asian countries for its high nutritive value and therapeutic properties. Despite its potent antitumor activity, the molecular mechanisms underlying its efficacy against CRC remain largely unexplored. This study aimed to elucidate the role of D. officinale in suppressing CRC through the induction of ferroptosis and its regulatory effects on glutathione peroxidase 4 (GPX4), a key mediator of ferroptosis suppression. In vitro assays were conducted using HCT116 and SW480 CRC cell lines. In vivo efficacy was assessed in BALB/c nude mice bearing CRC xenografts. Results indicated that D. officinale significantly inhibited CRC cell viability and proliferation in vitro and suppressed tumor growth in vivo. The induction of ferroptosis by D. officinale was evidenced by elevated levels of Fe²⁺, malondialdehyde, lipid peroxidation, and a depleted glutathione/oxidized glutathione disulfide ratio. These effects were reversed by ferroptosis inhibitors, including ferrostatin-1 and deferoxamine. D. officinale markedly downregulated GPX4 expression. Overexpression of GPX4 rescued D. officinale-induced ferroptosis, while its silencing exacerbated this effect. D. officinale suppresses CRC by triggering GPX4-dependent ferroptosis, offering a novel, naturally derived therapeutic strategy. These findings bridge traditional medicine and modern oncology, providing a foundation for the development of targeted CRC therapies.