Mebendazole inhibits growth of human adrenocortical carcinoma cell lines implanted in nude mice

Abstract

Adrenocortical carcinoma is a rare tumor of the adrenal gland which requires new therapeutic approaches as its early diagnosis is difficult and prognosis poor despite therapies used. Recently, mebendazole has been proved to be effective against different cancers. The aim of our study was to evaluate whether mebendazole may result therapeutically useful in the treatment of human adrenocortical carcinoma. We analyzed the effect of mebendazole on human adrenocortical carcinoma cells in vitro and after implantation in nude mice. In order to clarify mechanisms of mebendazole action, metastases formation, apoptosis and angiogenesis were also investigated. Mebendazole significantly inhibited cancer cells growth, both in vitro and in vivo, the effects being due to the induction of apoptosis. Moreover, mebendazole inhibited invasion and migration of cancer cells in vitro, and metastases formation in vivo. Overall, these data suggest that treatment with mebendazole, also in combination with standard therapies, could provide a new protocol for the inhibition of adrenocortical carcinoma growth.

Mebendazole Induces Apoptosis via Bcl-2 Inactivation in Chemoresistant Melanoma Cells

“…Benzimidazoles, specifically mebendazole and albendazole, have shown in vivo antitumor activity against a range of cancers, including hepatocellular, lung, and adrenocortical carcinoma (5,6,21). Mebendazole is more suited for clinical study than other benzimidazoles identified in our screen given its status as a marketed drug, its oral availability, and its favorable safety profile in long-term treatment regimens (19).…”

“…However, further assessment of mebendazole using an in vivo model of chemoresistant melanoma is a prerequisite before embarking on human studies. In light of promising in vivo studies showing the remarkable tumor growth inhibition of mebendazole in lung and adrenocortical carcinoma, it is reasonable to suggest that mebendazole will also be effective against malignant melanoma (5,6).…”

“…M-14 and SK-Mel-19 melanoma cell lines display resistance to a variety of traditional chemotherapies, including temozolomide, cisplatin, and arsenic trioxide (8)(9)(10). 5 Additionally, these cell lines were chosen based on their differential p53 status-M-14 expresses mutant p53 (11) and SK-Mel-19 expresses wild-type p53 (12)-to eliminate any dependence on the tumor suppressor. From a screen of the Spectrum Library (MicroSource Discovery Systems, Inc.), we identified 10 compounds that differentially inhibit cellular proliferation in melanoma cell lines (M-14 and SK-Mel-19) versus spontaneously immortalized melanocytes (melan-a; data not shown).…”

“…Antitumor activity of mebendazole has been previously described in lung and adrenocortical carcinomas (5,6). Furthermore, mebendazole has been shown to induce depolymerization of tubulin in a variety of cancer models (6,7).…”

Repurposing of Anthelminthics as Anticancer Drugs

“…The benzamidazole mebendazole significantly inhibited growth of adrenocortical carcinoma cells, both in vitro and in vivo, the effects being due to induction of apoptosis [19]. Moreover, mebendazole inhibited invasion and migration of cancer cells in vitro, and formation of metastases in vivo in experimental animals.…”