**Background**
Colorectal cancer (CRC) remains one of the most prevalent and lethal malignancies worldwide, characterized by high recurrence rates and complex signaling pathways. Signal transducer and activator of transcription 3 (STAT3) is frequently overactivated in various cancers, including CRC, where it promotes cell survival, proliferation, and resistance to apoptosis. Consequently, targeting the STAT3 signaling axis has become a primary focus for developing novel therapeutic strategies to inhibit tumor growth. Beyond traditional chemotherapy, the repurposing of anthelmintic drugs has revealed significant potential in oncology. In this context, we will introduce an antitumor agent with potent inhibitory effects on STAT3 and microtubule function – Flubendazole.
**Definition**
Flubendazole is an anthelmintic and antitumor drug that acts by altering microtubule structure and inhibiting tubulin polymerization. It functions as a STAT3 inhibitor, effectively inducing apoptosis and autophagy in various cancer cell lines.
**In Vitro and In Vivo Studies**
According to the Flubendazole description, this compound exerts its effects by blocking the STAT3 signaling axis and inducing P53 expression while reducing Cyclin B1 and p-cdc2 expression. Flubendazole in vitro studies have demonstrated significant efficacy across multiple cell lines. In human CRC cells (HCT116, RKO, and SW480), Flubendazole (0-400 μM; 48 h) inhibited cell proliferation with IC50 values ranging from 2-5 μM. Furthermore, concentrations of 0.3-1.2 μM over 48 hours increased the proportion of apoptotic cells and enhanced caspase-3 activity. Notably, Flubendazole Autophagy was observed at concentrations of 0.3-1.2 μM (24 h), where it initiated autophagy by inactivating mTOR and P62 and upregulating LC3-I/II. Western blot analysis confirmed a dose- and time-dependent reduction of phosphorylated STAT3 (P-STAT3) and decreased expression of MCL1 and survivin. Additionally, the compound showed potent anticancer activity against BT-549 (IC50 = 0.125 μM), Hs-578T (IC50 = 0.125 μM), and MDA-MB-231 (IC50 = 0.25-0.75 μM) cells.
Flubendazole in vivo research using female BALB/c athymic nude mice bearing HCT116 xenografts showed that administration of 10 or 30 mg/kg via intraperitoneal injection every other day for 14 days markedly reduced tumor volume. These results were associated with a significant reduction in P-STAT3 protein levels and the promotion of apoptosis and autophagy within the tumor tissue. In conclusion, Flubendazole is a versatile antitumor agent that inhibits tumor growth by targeting the STAT3 pathway and disrupting microtubule function.
Keywords
Flubendazole, 31430-15-6, Parasite, Microtubule/Tubulin, STAT, MDM-2/p53, Apoptosis, Autophagy, Anthelmintic, microtubule, tubulin polymerization, CRC, Cyclin B1, p-cdc2, worm, intestinal parasites, colorectal cancer, Inhibitor, inhibitor, inhibit
References
[1] Zhou X, et al. Flubendazole inhibits glioma proliferation by G2/M cell cycle arrest and pro-apoptosis. Cell Death Discov. 2018 Feb 14;4:18.
[2] Shichong Lin, et al. Flubendazole demonstrates valid antitumor effects by inhibiting STAT3 and activating autophagy. J Exp Clin Cancer Res. 2019 Jul 8;38(1):293.