The Antitumor Potentials of Benzimidazole Anthelmintics as Repurposing Drugs

Abstract

The development of refractory tumor cells limits therapeutic efficacy in cancer by activating mechanisms that promote cellular proliferation, migration, invasion, metastasis, and survival. Benzimidazole anthelmintics have broad-spectrum action to remove parasites both in human and veterinary medicine. In addition to being antiparasitic agents, benzimidazole anthelmintics are known to exert anticancer activities, such as the disruption of microtubule polymerization, the induction of apoptosis, cell cycle (G2/M) arrest, anti-angiogenesis, and blockage of glucose transport. These antitumorigenic effects even extend to cancer cells resistant to approved therapies and when in combination with conventional therapeutics, enhance anticancer efficacy and hold promise as adjuvants. Above all, these anthelmintics may offer a broad, safe spectrum to treat cancer, as demonstrated by their long history of use as antiparasitic agents. The present review summarizes central literature regarding the anticancer effects of benzimidazole anthelmintics, including albendazole, parbendazole, fenbendazole, mebendazole, oxibendazole, oxfendazole, ricobendazole, and flubendazole in cancer cell lines, animal tumor models, and clinical trials. This review provides valuable information on how to improve the quality of life in patients with cancers by increasing the treatment options and decreasing side effects from conventional therapy.

Keywords: Anthelmintics; Benzimidazole; Cancer; Therapeutics.

Figure 1. Structures of benzimidazole anthelmintics.

Figure 2. Summarized schemes for the antitumorigenicity of benzimidazole anthelmintics in cancer. Light green boxes, inhibited biological aspects; pink boxes, induced biological aspects; red letters, upregulated signalings and reactions; blue letters, downregulated signalings and reactions. See Tables 1 and 2 for genes and proteins.