Induction of apoptosis in murine leukemia by diarylheptanoids from Curcuma comosa Roxb. |
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Authors: | Surawat Jariyawat Thanapol Thammapratip Kanoknetr Suksen Podchanart Wanitchakool Jintapat Nateewattana Arthit Chairoungdua Apichart Suksamrarn Pawinee Piyachaturawat |
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Institution: | (1) Department of Physiology, Faculty of Science, Mahidol University, Rama 6 Rd, Bangkok, 10400, Thailand;(2) Graduate Programme in Toxicology, Faculty of Science, Mahidol University, Rama 6 Rd, Bangkok, 10400, Thailand;(3) Department of Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok, 10240, Thailand; |
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Abstract: | Diarylheptanoids, isolated from the rhizome of Curcuma comosa Roxb., have several biological activities including anti-oxidant and anti-inflammation. The present study investigated the
effect of five diarylheptanoids isolated from C. comosa rhizome on the proliferation of murine P388 leukemic cells. Compound-092, (3S)-1-(3,4-dihydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol, bearing a catechol moiety, was the most potent diarylheptanoid (IC50 of 4 μM) in inhibiting P388 leukemic cell viability by causing DNA breakage and inducing apoptosis. Apoptotic cell death
was characterized by the presence of chromatin condensation, formation of apoptotic bodies, DNA fragmentation, and externalization
of plasma membrane phosphatidylserine. This compound increased caspase-3 activity about fivefold above the untreated control,
decreased the intracellular reduced glutathione level, and impaired mitochondrial transmembrane potential. In the presence
of Cu(II) ion, the compound exhibited a pro-oxidant activity causing DNA strand breakage and enhancing the anti-proliferative
activity. The results provide evidence for the pro-oxidant activity of the diarylheptanoid bearing a catechol moiety in the
induction of apoptosis in murine P388 leukemia. |
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