Kwang-Youn Kim1, Kwang Il Park2, Sang-Hun Kim3, Sun-Nyoung Yu3, Deokjae Lee4, Young Woo Kim1, Kyung Tae Noh5, Jin Yeul Ma2, Young-Kyo Seo4, Soon-Cheol Ahn6. 1. Department of Herbal Formula, Medical Research Center (MRC-GHF), College of Oriental Medicine, Daegu Haany University, Gyeongsan, Republic of Korea. 2. Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Daegu, Republic of Korea. 3. Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Republic of Korea. 4. School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea. 5. Department of Infectious Diseases, Armed Forces Medical Research Institute, Daejeon, Republic of Korea. 6. Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Republic of Korea ahnsc@pusan.ac.kr.
Abstract
BACKGROUND/AIM: Chemotherapy is a critical option for cancer treatment. However, consistent exposure to chemotherapeutic drugs promotes chemoresistance in cancer cells through diverse mechanisms. Accordingly, we investigated whether salinomycin, a monocarboxylic ionophore, could induce apoptosis in aggressive breast cancer cells or not, as well as its underlying mechanism. MATERIALS AND METHODS: Using salinomycin on two breast cancer cell lines, MCF-7 cells and MDA-MB-231 cells, cell viability, annexin V/propidium iodide staining, acridine orange staining, caspase-3/9 activity, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were assayed. RESULTS: In this study, salinomycin induced apoptosis and autophagy in MDA-MB-231 cells. Salinomycin-mediated ROS production led to mitochondrial dysfunction in MDA-MB-231 cells. Interestingly, treatment of N-acetyl-L-cysteine (NAC), a scavenger of ROS, attenuated salinomycin-induced apoptosis and autophagy. Moreover, autophagy inhibition is involved in acceleration of apoptosis induced by salinomycin. CONCLUSION: Salinomycin induced apoptosis and ROS production, that were blocked by autophagy, thus resulting in protecting cancer cells. This crosstalk of two different physiological responses (autophagy and apoptosis) induced by salinomycin might play pivotal roles in the relationship between autophagy and apoptosis of cancer cells. Copyright
BACKGROUND/AIM: Chemotherapy is a critical option for cancer treatment. However, consistent exposure to chemotherapeutic drugs promotes chemoresistance in cancer cells through diverse mechanisms. Accordingly, we investigated whether salinomycin, a monocarboxylic ionophore, could induce apoptosis in aggressive breast cancer cells or not, as well as its underlying mechanism. MATERIALS AND METHODS: Using salinomycin on two breast cancer cell lines, MCF-7 cells and MDA-MB-231 cells, cell viability, annexin V/propidium iodide staining, acridine orange staining, caspase-3/9 activity, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were assayed. RESULTS: In this study, salinomycin induced apoptosis and autophagy in MDA-MB-231 cells. Salinomycin-mediated ROS production led to mitochondrial dysfunction in MDA-MB-231 cells. Interestingly, treatment of N-acetyl-L-cysteine (NAC), a scavenger of ROS, attenuated salinomycin-induced apoptosis and autophagy. Moreover, autophagy inhibition is involved in acceleration of apoptosis induced by salinomycin. CONCLUSION:Salinomycin induced apoptosis and ROS production, that were blocked by autophagy, thus resulting in protecting cancer cells. This crosstalk of two different physiological responses (autophagy and apoptosis) induced by salinomycin might play pivotal roles in the relationship between autophagy and apoptosis of cancer cells. Copyright
Authors: Johannes Klose; Engin Guerlevik; Tina Trostel; Florian Kühnel; Thomas Schmidt; Martin Schneider; Alexis Ulrich Journal: Oncotarget Date: 2017-12-16
Authors: Alicja Urbaniak; Megan R Reed; Daniel Fil; Anika Moorjani; Sarah Heflin; Michał Antoszczak; Michał Sulik; Adam Huczyński; Michalina Kupsik; Robert L Eoff; Melanie C MacNicol; Timothy C Chambers; Angus M MacNicol Journal: Biomed Pharmacother Date: 2021-06-12 Impact factor: 7.419