Ming-Ju Hsieh1, Che-Wei Wang2, Jen-Tsun Lin3, Yi-Ching Chuang4, Yi-Ting Hsi4, Yu-Sheng Lo4, Chia-Chieh Lin4, Mu-Kuan Chen5. 1. Oral Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan; Department of Holistic Wellness, Mingdao University, Changhua 52345, Taiwan. Electronic address: 170780@cch.org.tw. 2. Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, Changhua 500, Taiwan. 3. Division of Hematology and Oncology, Department of Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan. 4. Oral Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan. 5. Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, Changhua 500, Taiwan. Electronic address: 53780@cch.org.tw.
Abstract
BACKGROUND: Developing resistance to chemotherapeutic drugs has become a major problem in the management of nasopharyngeal carcinoma (NPC). To overcome this issue, use of natural plant products as chemosensitizers is gaining importance at a fast pace. HYPOTHESIS/ PURPOSE: The present study was designed to evaluate the cytotoxic effect and mode of action of a natural pentacyclic triterpenoid, celastrol, on cisplatin-resistant NPC cells. RESULTS: Study results revealed that celastrol treatment significantly reduced the viability of NPC cells in dose and time dependent manners, as compared to untreated control cells. The cytotoxic effect of celastrol was mediated by cell cycle arrest at G2/M phase and induction of intrinsic and extrinsic apoptotic pathways. With further analysis, we observed that celastrol-induced activation of caspases was accompanied by increased phosphorylation of MAPK pathway proteins, p38, ERK1/2. CONCLUSION: Taken together, our observation provides a novel insight on use of a natural plant product, celastrol, in the management of chemoresistant NPC.
BACKGROUND: Developing resistance to chemotherapeutic drugs has become a major problem in the management of nasopharyngeal carcinoma (NPC). To overcome this issue, use of natural plant products as chemosensitizers is gaining importance at a fast pace. HYPOTHESIS/ PURPOSE: The present study was designed to evaluate the cytotoxic effect and mode of action of a natural pentacyclic triterpenoid, celastrol, on cisplatin-resistant NPC cells. RESULTS: Study results revealed that celastrol treatment significantly reduced the viability of NPC cells in dose and time dependent manners, as compared to untreated control cells. The cytotoxic effect of celastrol was mediated by cell cycle arrest at G2/M phase and induction of intrinsic and extrinsic apoptotic pathways. With further analysis, we observed that celastrol-induced activation of caspases was accompanied by increased phosphorylation of MAPK pathway proteins, p38, ERK1/2. CONCLUSION: Taken together, our observation provides a novel insight on use of a natural plant product, celastrol, in the management of chemoresistant NPC.
Authors: Sabrina Borchert; Pia-Maria Suckrau; Michael Wessolly; Elena Mairinger; Balazs Hegedus; Thomas Hager; Thomas Herold; Wildfried E E Eberhardt; Jeremias Wohlschlaeger; Clemens Aigner; Agnes Bankfalvi; Kurt Werner Schmid; Robert F H Walter; Fabian D Mairinger Journal: J Oncol Date: 2019-12-23 Impact factor: 4.375
Authors: Elaine C D Gonçalves; Gabriela M Baldasso; Maíra A Bicca; Rodrigo S Paes; Raffaele Capasso; Rafael C Dutra Journal: Molecules Date: 2020-03-29 Impact factor: 4.411