Halicin Reduces the Warburg Effect and Overcomes Drug Resistance by Activating the Pyruvate Kinase M2 Pathway for Triple-Negative Breast Cancer Treatment

Breast cancer represents the most common cancer among women worldwide. Triple-negative breast cancer (TNBC), a particularly aggressive, metastatic, and drug-resistant subtype of breast cancer, poses a significant clinical challenge because of its resistance to treatment. The efficacy of commonly employed chemotherapeutic agents, such as paclitaxel, is severely limited. In this study, we identified the chemical compound Halicin, which inhibits the proliferation of various cancers, including TNBC. <i>In vitro</i> and <i>in vivo</i> experiments demonstrated that Halicin could activate pyruvate kinase M2 from its inactive dimers to active tetramers, changing the metabolism of tumor cells and suppressing tumor growth. Moreover, Halicin disrupted mitochondria and downregulated the antiapoptotic gene Bcl-2 to overcome multidrug resistance. Further experiments revealed that Halicin inhibits the growth of orthotopic breast tumors through intraperitoneal injection. The discovery of Halicin as an anticancer drug holds great promise for the treatment of TNBC.