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.
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Authors | Kok 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 |
Journal | Food 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 |
PMID | 22613213
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Ltd. All rights reserved. |
Chemical References |
- Reactive Oxygen Species
- Xanthones
- inophyllin A
- Caspases
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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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