title: Induction of apoptosis in murine leukemia by diarylheptanoids from Curcuma comosa Roxb.
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 (IC(50) 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.
authors.affiliation: Department of Physiology, Mahidol University, Bangkok, Thailand.
authors.forename: Surawat
authors.initials: S
authors.lastname: Jariyawat
authors.forename: Thanapol
authors.initials: T
authors.lastname: Thammapratip
authors.forename: Kanoknetr
authors.initials: K
authors.lastname: Suksen
authors.forename: Podchanart
authors.initials: P
authors.lastname: Wanitchakool
authors.forename: Jintapat
authors.initials: J
authors.lastname: Nateewattana
authors.forename: Arthit
authors.initials: A
authors.lastname: Chairoungdua
authors.forename: Apichart
authors.initials: A
authors.lastname: Suksamrarn
authors.forename: Pawinee
authors.initials: P
authors.lastname: Piyachaturawat
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D030024:Curcuma / Q000737:chemistry*; D053938:DNA Fragmentation / Q000187:drug effects; D036381:Diarylheptanoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016877:Oxidants / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000032:analysis; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism; D027343:Rhizome / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002843:Chromatin; D036381:Diarylheptanoids; D016877:Oxidants; D010718:Phosphatidylserines; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D053148:Caspase 3; D005978:Glutathione