Flubendazole overcomes trastuzumab resistance by targeting cancer stem-like properties and HER2 signaling in HER2-positive breast cancer

Flubendazole elicits anti‐metastatic effects in triple‐negative breast cancer via STAT3 inhibition

“…Pretreatment with the pan‐caspase inhibitor (Z‐VAD‐fmk) significantly suppressed catalytic activity and cleavage of caspase‐3 and caspase‐7, and apoptotic cell death following FLU challenge, indicating that FLU‐induced apoptosis requires the activation of effector caspases in TNBC cells. We previously reported that FLU does not impact cell viability or apoptosis in normal murine mammary gland NMuMG cells or normal human embryonic kidney HEK 293 T cells …”

“…In this study, exposure to FLU (0.1–0.5 µM) at concentrations well below the maximum pharmacologically achievable dose (∼1.1 µM), was shown to result in cell growth inhibition and G2/M phase cell cycle arrest leading to mitotic catastrophe in TNBC cells. FLU disrupts microtubule structure by tubulin degradation and elicits anti‐proliferative effects in several cancer cell types including leukemia, myeloma, neuroblastoma, intestinal and breast cancer . Although FLU exhibits anti‐cancer activity via inhibition of tubulin polymerization, the cellular mechanism underlying its apoptotic effect in TNBC cells has not been fully understood.…”

“…FLU disrupts microtubule structure by tubulin degradation and elicits anti-proliferative effects in several cancer cell types including leukemia, myeloma, neuroblastoma, intestinal and breast cancer. [21][22][23] Although FLU exhibits anti-cancer activity via inhibition of tubulin polymerization, the cellular mechanism underlying its apoptotic effect in TNBC cells has not been fully understood. Our results showed that FLU induced cell death, marked by apoptotic features and accompanied by sub-G1 accumulation, externalization of annexin V, activation of caspase-3 and 27, and PARP cleavage in TNBC cells.…”

“…The favorable safety profile of the drug has been well established in preclinical and clinical studies . Emerging preclinical evidence suggests that FLU may be a potential anticancer drug, due to its ability to inhibit tubulin polymerization, leading to mitotic catastrophe . However, the precise mechanisms underlying FLU‐induced antitumor effects have not been elucidated.…”

“…[18][19][20] Emerging preclinical evidence suggests that FLU may be a potential anticancer drug, due to its ability to inhibit tubulin polymerization, leading to mitotic catastrophe. [21][22][23] However, the precise mechanisms underlying FLU-induced antitumor effects have not been elucidated. In the present study, we sought to characterize the mechanism of action responsible for FLU's novel effects in targeting BCSC-like properties and the STAT3 signaling pathway in TNBC, as well as its effects on tumor burden, angiogenesis and metastasis.…”