title: 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.
authors.affiliation: Toxicology Laboratory, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Wilayah Persekutuan, Malaysia. chan@fskb.ukm.my
authors.forename: Kok Meng
authors.initials: KM
authors.lastname: Chan
authors.forename: Ruhana
authors.initials: R
authors.lastname: Hamzah
authors.forename: Amira Abd
authors.initials: AA
authors.lastname: Rahaman
authors.forename: Vivien Yi Mian
authors.initials: VY
authors.lastname: Jong
authors.forename: Heng Yen
authors.initials: HY
authors.lastname: Khong
authors.forename: Nor Fadilah
authors.initials: NF
authors.lastname: Rajab
authors.forename: Gwendoline Cheng Lian
authors.initials: GC
authors.lastname: Ee
authors.forename: Salmaan Hussain
authors.initials: SH
authors.lastname: Inayat-Hussain
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D004249:DNA Damage; D004789:Enzyme Activation; D005434:Flow Cytometry; D006801:Humans; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D017382:Reactive Oxygen Species; D044004:Xanthones; C511327:inophyllin A; D020169:Caspases