1. Department of Pathology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan.
2. Department of Food Nutrition and Health Biotechnology, Asia University, Taichung, Taiwan.
3. Department of Nursing, Min-Hwei College of Health Care Management, Tainan 73658, Taiwan.
4. Department of Medical Research, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan.
5. Department of Urology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan.
6. Department of Microbiology and Immunology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
7. Master of Science Program in Tropical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Bladder carcinoma is one of the most common malignancies worldwide, and >90% of all bladder cancers are classified as urothelial carcinomas (UC). Surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy are evidence-based treatments that are administered depending on the clinical stage of UC. All these treatments exhibited limited effects in cases of metastatic UC, and UC with specific location, invasiveness, and recurrence. Therefore, a new therapeutic strategy for UC is urgently needed.
Ivermectin, an avermectin derivative, has been reported to be effective against various parasites, and its pharmacokinetic and pharmacodynamic properties as well as safety are well understood in humans. Recently, ivermectin was shown to exhibit therapeutic benefits against various virus infections in vitro, and anticancer activity against various human cancer cells. This study aimed to investigate the anticancer effects of ivermectin in human UC cells. Ivermectin inhibited growth, regulated the cell cycle, and induced apoptosis in human UC cells. It also induced the activation of both extrinsic and intrinsic caspase-dependent apoptotic pathways. Further investigation revealed that ivermectin induced apoptosis in UC cells is mediated via c-Jun N-terminal kinase signaling. Herein, we demonstrated that ivermectin can be used as a new therapeutic agent for treating UC cells.
Keywords: bladder cancer, ivermectin, anticancer activity, apoptosis