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

Chan Kok Meng, Ruhana Hamzah, Amira Abd Rahaman, Vivien Yi Mian Jong, Heng Yen Khong, Nor Fadilah Rajab, Gwendoline Cheng Lian Ee, Salmaan Hussain Inayat-Hussain

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2916-2922
Number of pages7
JournalFood and Chemical Toxicology
Volume50
Issue number8
DOIs
Publication statusPublished - Aug 2012

Fingerprint

T-Cell Leukemia
lymphocytic leukemia
Oxidative stress
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Oxidative Stress
oxidative stress
apoptosis
DNA damage
Apoptosis
thiols
cell death
caspase-2
Calophyllum inophyllum
cells
xanthone
DNA Damage
phosphatidylserines
Jurkat Cells
caspase-3
membrane potential

Keywords

  • Caspases
  • DNA damage
  • Inophyllin A
  • Mitochondria-mediated apoptosis
  • Reactive oxygen species

ASJC Scopus subject areas

  • Food Science
  • Toxicology

Cite this

The pyranoxanthone inophyllin A induces oxidative stress mediated-apoptosis in Jurkat T lymphoblastic leukemia cells. / Kok Meng, Chan; Hamzah, Ruhana; Rahaman, Amira Abd; Jong, Vivien Yi Mian; Khong, Heng Yen; Rajab, Nor Fadilah; Ee, Gwendoline Cheng Lian; Inayat-Hussain, Salmaan Hussain.

In: Food and Chemical Toxicology, Vol. 50, No. 8, 08.2012, p. 2916-2922.

Research output: Contribution to journalArticle

Kok Meng, Chan ; Hamzah, Ruhana ; Rahaman, Amira Abd ; Jong, Vivien Yi Mian ; Khong, Heng Yen ; Rajab, Nor Fadilah ; Ee, Gwendoline Cheng Lian ; Inayat-Hussain, Salmaan Hussain. / The pyranoxanthone inophyllin A induces oxidative stress mediated-apoptosis in Jurkat T lymphoblastic leukemia cells. In: Food and Chemical Toxicology. 2012 ; Vol. 50, No. 8. pp. 2916-2922.
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