Anthelmintic drug albendazole arrests human gastric cancer cells at the mitotic phase and induces apoptosis

Abstract

As microtubules have a vital function in the cell cycle, oncologists have developed microtubule inhibitors capable of preventing uncontrolled cell division, as in the case of cancer. The anthelmintic drug albendazole (ABZ) has been demonstrated to inhibit hepatocellular, ovarian and prostate cancer cells via microtubule targeting. However, its activity against human gastric cancer (GC) cells has remained to be determined. In the present study, ABZ was used to treat GC cells (MKN-45, SGC-7901 and MKN-28). A a CCK-8 cell proliferation assay was performed to assess the effects of ABZ on cell viability and cell cycle changes were assessed using flow cytometry. SGC-7901 cells were selected for further study, and flow cytometry was employed to determine the apoptotic rate, immunofluorescence analysis was employed to show changes of the microtubule structure as well as the subcellular localization and expression levels of cyclin B1, and western blot analysis was used to identify the dynamics of microtubule assembly. The expression levels of relevant proteins, including cyclin B1 and Cdc2, the two subunits of mitosis-promoting factor as well as apoptosis-asociated proteins were also assessed by western blot analysis. The results showed that ABZ exerted its anti-cancer activity in GC cell lines by disrupting microtubule formation and function to cause mitotic arrest, which is also associated with the accumulation of cyclin B1, and consequently induces apoptosis.

Antitumor Effect of Albendazole on Cutaneous Squamous Cell Carcinoma (SCC) Cells

“…Despite the several treatment modalities for cutaneous SCC, there is still a demand for novel pharmacotherapy that is more efficacious and safe. The repurposing/repositioning of drugs that have already been approved for other diseases is considered as an alternative way to develop new drugs, because time-consuming and expensive process can be avoided or shortened [21, 22]. In this study, we demonstrated that an antiparasitic drug albendazole has the potential to induce apoptosis of cutaneous SCC cells via triggering ER stress and reduces the stemness of SCC cells via regulation of β -catenin signaling.…”

Solid Polymeric Nanoparticles of Albendazole: Synthesis, Physico-Chemical Characterization and Biological Activity

“…Any drug that can activate through various mechanisms the apoptotic pathway or inhibit the endogenous anti-apoptotic molecules is a strong candidate to become an efficient anticancer agent. As reported by a great number of studies, ABZ can induce apoptosis through various mechanisms; in human gastric cancer cells, the ABZ anticancer activity emerged due to its ability to interfere with microtubule formation and function, causing mitotic arrest and subsequently inducing apoptosis [78]. The same microtubule disrupting ability was employed as anticancer treatment by Patel et al in small cell lung cancer and metastatic melanoma cell lines [8].…”

The Antitumor Potentials of Benzimidazole Anthelmintics as Repurposing Drugs

“…Supplementary Table 1 ( 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 ) summarizes the antitumorigenicity of benzimidazole anthelmintics on cancer cell lines. Benzimidazole anthelmintics inhibit the progression of cancer through a variety of mechanisms.…”