LingZhi (Ganoderma lucidum) has been used as a therapeutic agent for decades, but the antitumor potency of LingZhi oligopeptides (LZOs) was not well explored. In current study, ten novel LZO amino acid sequences were identified, and anticancer potency was evaluated. We found that LZO-3 [EGHGF] significantly triggered A549 cell apoptosis via mitochondrial dysregulation, as evidenced by caspases activation, mitochondrial membrane potential collapse, Bcl-2/Bax ratio alteration, and cytochrome c release. Further, the down-regulation of Trx/TrxR reductase and the improvement of the MDM2/p53 state also contributed to the LZO-3-induced cell apoptosis. Notably, our findings provide evidence for the novel potency of LZOs, which could be developed as promising chemotherapeutic agents against lung cancer.
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