Optimizing adjuvant inhaled chemotherapy: Synergistic enhancement in paclitaxel cytotoxicity by flubendazole nanocrystals in a cycle model approach

Miyagi, Mariana Yasue Saito; Faria, Rafael de Oliveira; Souza, Gabriel Batista de; Lameu, Claudiana; Tagami, Tatsuaki; Ozeki, Tetsuya; Bezzon, Vinícius Danilo Nonato; Yukuyama, Megumi Nishitani; Bou‐Chacra, Nádia Araci; Araujo, Gabriel Lima Barros de

doi:10.1016/j.ijpharm.2023.123324

Cited by 2 publications

(1 citation statement)

References 65 publications

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“…In addition, flubendazole has been recognized as a microtubule inhibitor that can disrupt microtubule polymerization by binding to free tubulin dimers at the colchicine binding site [38][39][40], whereas paclitaxel inhibits the microtubule depolymerisation by binding to tubulin monomers at another diverse site [41]. Interestingly, orally inhalable flubendazole nanocrystals also synergistically enhance the cytotoxicity of paclitaxel on A549 lung cancer cells, reduce adverse reactions, and solve the problems of poor solubility and bioavailability of flubendazole in clinical practice [42]. Therefore, the combination of flubendazole and paclitaxel is expected to have largely additive anti-tumor effects.…”

Section: Discussionmentioning

confidence: 99%

Flubendazole Enhances the Inhibitory Effect of Paclitaxel via HIF1α/PI3K/AKT Signaling Pathways in Breast Cancer

Zhou,

Liao,

et al. 2023

IJMS

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Paclitaxel, a natural anticancer drug, is widely recognized and extensively utilized in the treatment of breast cancer (BC). However, it may lead to certain side effects or drug resistance. Fortunately, combination therapy with another anti-tumor agent has been explored as an option to improve the efficacy of paclitaxel in the treatment of BC. Herein, we first evaluated the synergistic effects of paclitaxel and flubendazole through combination index (CI) calculations. Secondly, flubendazole was demonstrated to synergize paclitaxel-mediated BC cell killing in vitro and in vivo. Moreover, we discovered that flubendazole could reverse the drug resistance of paclitaxel-resistant BC cells. Mechanistically, flubendazole was demonstrated to enhance the inhibitory effect of paclitaxel via HIF1α/PI3K/AKT signaling pathways. Collectively, our findings demonstrate the effectiveness of flubendazole in combination with paclitaxel for treating BC, providing an insight into exploiting more novel combination therapies for BC in the future.

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Section: Discussionmentioning

confidence: 99%

Flubendazole Enhances the Inhibitory Effect of Paclitaxel via HIF1α/PI3K/AKT Signaling Pathways in Breast Cancer

Zhou,

Liao,

et al. 2023

IJMS

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Anticancer role of flubendazole: Effects and molecular mechanisms (Review)

Xing,

Zhou,

Peng

et al. 2024

Oncol Lett

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Flubendazole, an anthelmintic agent with a well-established safety profile, has emerged as a promising anticancer drug that has demonstrated efficacy against a spectrum of cancer types over the past decade. Its anticancer properties encompass a multifaceted mechanism of action, including the inhibition of cancer cell proliferation, disruption of microtubule dynamics, regulation of cell cycle, autophagy, apoptosis, suppression of cancer stem cell characteristics, promotion of ferroptosis and inhibition of angiogenesis. The present review aimed to provide a comprehensive overview of the molecular underpinnings of the anticancer activity of flubendazole, highlighting key molecules and regulatory pathways. Given the breadth of the potential of flubendazole, further research is imperative to identify additional cancer types sensitive to flubendazole, refine experimental methodologies for enhancing its reliability, uncover synergistic drug combinations, improve its bioavailability and explore innovative administration methods. The present review provided a foundation for future studies on the role of flubendazole in oncology and described its molecular mechanisms of action.

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Optimizing adjuvant inhaled chemotherapy: Synergistic enhancement in paclitaxel cytotoxicity by flubendazole nanocrystals in a cycle model approach

Cited by 2 publications

References 65 publications

Flubendazole Enhances the Inhibitory Effect of Paclitaxel via HIF1α/PI3K/AKT Signaling Pathways in Breast Cancer

Flubendazole Enhances the Inhibitory Effect of Paclitaxel via HIF1α/PI3K/AKT Signaling Pathways in Breast Cancer

Anticancer role of flubendazole: Effects and molecular mechanisms (Review)

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