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The pyranoxanthone inophyllin A induces oxidative stress mediated-apoptosis in Jurkat T lymphoblastic leukemia cells.

Abstract
Inophyllin A (INO-A), a pyranoxanthone isolated from the roots of Calophyllum inophyllum represents a new xanthone with potential chemotherapeutic activity. In this study, the molecular mechanism of INO-A-induced cell death was investigated in Jurkat T lymphoblastic leukemia cells. Assessment of phosphatidylserine exposure confirmed apoptosis as the primary mode of cell death in INO-A-treated Jurkat cells. INO-A treatment for only 30 min resulted in a significant increase of tail moment which suggests that DNA damage is an early apoptotic signal. Further flow cytometric assessment of the superoxide anion level confirmed that INO-A induced DNA damage was mediated with a concomitant generation of reactive oxygen species (ROS). Investigation on the thiols revealed an early decrease of free thiols in 30 min after 50 μM INO-A treatment. Using tetramethylrhodamine ethyl ester, a potentiometric dye, the loss of mitochondrial membrane potential (MPP) was observed in INO-A-treated cells as early as 30 min. The INO-A-induced apoptosis progressed with the simultaneous activation of caspases-2 and -9 which then led to the processing of caspase-3. Taken together, these data demonstrate that INO-A induced early oxidative stress, DNA damage and loss of MMP which subsequently led to the activation of an intrinsic pathway of apoptosis in Jurkat cells.
AuthorsKok Meng Chan, Ruhana Hamzah, Amira Abd Rahaman, Vivien Yi Mian Jong, Heng Yen Khong, Nor Fadilah Rajab, Gwendoline Cheng Lian Ee, Salmaan Hussain Inayat-Hussain
JournalFood and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 50 Issue 8 Pg. 2916-22 (Aug 2012) ISSN: 1873-6351 [Electronic] England
PMID22613213 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier Ltd. All rights reserved.
Chemical References
  • Reactive Oxygen Species
  • Xanthones
  • inophyllin A
  • Caspases
Topics
  • Apoptosis (drug effects)
  • Caspases (metabolism)
  • DNA Damage
  • Enzyme Activation
  • Flow Cytometry
  • Humans
  • Jurkat Cells
  • Leukemia, T-Cell (enzymology, metabolism, pathology)
  • Oxidative Stress (drug effects)
  • Reactive Oxygen Species (metabolism)
  • Xanthones (pharmacology)

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