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

Qing-Ling Zhang,Xue Mei Li,Chang Deok Kim,Jae Kyung Lee,De-De Lian,Tae-Jin Yoon,Jeung-Hoon Lee,Ming Ji Zhu,Ri-Hua Jiang

doi:10.1155/2019/3689517

Abstract

Drug repurposing and/or repositioning is an alternative method to develop new treatment for certain diseases. Albendazole was originally developed as an anthelmintic medication, and it has been used to treat a variety of parasitic infestations. In this study, we investigated the antitumor effect of albendazole and putative action mechanism. Results showed that albendazole dramatically decreased the cell viability of SCC cell lines (SCC12 and SCC13 cells). Albendazole increased apoptosis-related signals, including cleaved caspase-3 and PARP-1 in a dose-dependent fashion. The mechanistic study showed that albendazole induced endoplasmic reticulum (ER) stress, evidenced by increase of CHOP, ATF-4, caspase-4, and caspase-12. Pretreatment with ER stress inhibitor 4-PBA attenuated albendazole-induced apoptosis of SCC cells. In addition, albendazole decreased the colony-forming ability of SCC cells, together with inhibition of Wnt/β-catenin signaling. These results indicate that albendazole shows an antitumor effect via regulation of ER stress and cancer stemness, suggesting that albendazole could be repositioned for cutaneous SCC treatment.

Highlights

Cutaneous squamous cell carcinoma (SCC) is the cancer originated from upper layers of skin epidermis
To verify whether albendazole induces apoptosis of SCC12 and SCC13 cells, we carried out transferase dUTP nick-end labeling (TUNEL) staining
We demonstrated that an antiparasitic drug albendazole has the potential to induce apoptosis of cutaneous SCC cells via triggering endoplasmic reticulum (ER) stress and reduces the stemness of SCC cells via regulation of β-catenin signaling

Summary

Introduction

Cutaneous squamous cell carcinoma (SCC) is the cancer originated from upper layers of skin epidermis. We attempted to screen the antitumor materials using a commercially available drug library and found that albendazole had a potential to induce the apoptosis of cutaneous SCC cells. Albendazole inhibits growth of non-small cell lung cancer cells by suppressing hypoxia-inducible factor-1-α (HIF-1-α) activity and vascular endothelial growth factor (VEGF) expression [11]. In another example, albendazole inhibits the growth of metastatic melanoma and increases sensibility of cancer cells to radiation [12]. The antitumor ability has been recognized in other systems, the effects of albendazole on cutaneous SCC cells and the action mechanism remain to be investigated

Materials and Methods

Results

Discussion