Chebulinic Acid Isolated From the Fruits of Terminalia chebula Specifically Induces Apoptosis in Acute Myeloid Leukemia Cells |
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Authors: | Stuti Chhabra Tripti Mishra Yogesh Kumar Gatha Thacker Sanjeev Kanojiya Naibedya Chattopadhyay Tadigoppula Narender Arun Kumar Trivedi |
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Institution: | 1. Biochemistry Division, CSIR‐Central Drug Research Institute (CSIR‐CDRI), Lucknow, India;2. Medicinal and Process Chemistry Division, CSIR‐Central Drug Research Institute (CSIR‐CDRI), Lucknow, India;3. Sophisticated Analytical Instrument Facility, CSIR‐Central Drug Research Institute, Lucknow, India;4. Division of Endocrinology and Center for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR‐Central Drug Research Institute (CSIR‐CDRI), Lucknow, India |
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Abstract: | Chebulinic acid, an ellagitannin found in the fruits of Terminalia chebula, has been extensively used in traditional Indian system of medicine. It has shown to have various biological activities including antitumor activity. The present study aims to investigate the cytotoxic potential of chebulinic acid in human myeloid leukemia cells. Interestingly, chebulinic acid caused apoptosis of acute promyelocytic leukemia HL‐60 and NB4 cells but not K562 cells. In vitro antitumor effects of chebulinic acid were investigated by using various acute myeloid leukemia cell lines. Chebulinic acid treatment to HL‐60 and NB4 cells induced caspase activation, cleavage of poly(ADP‐ribose) polymerase, DNA fragmentation, chromatin condensation, and changes in the mitochondrial membrane permeability. Additionally, inhibition of caspase activation drastically reduced the chebulinic acid‐induced apoptosis of acute promyelocytic leukemia cells. Our data also demonstrate that chebulinic acid‐induced apoptosis in HL‐60 and NB4 cells involves activation of extracellular signal‐regulated kinases, which, when inhibited with ERK inhibitor PD98059, mitigates the chebulinic acid‐induced apoptosis. Taken together, our findings exhibit the selective potentiation of chebulinic acid‐induced apoptosis in acute promyelocytic leukemia cells. Copyright © 2017 John Wiley & Sons, Ltd. |
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Keywords: | chebulinic acid acute promyelocytic leukemia apoptosis capases HL‐60 NB4 |
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