Induction of apoptosis in murine leukemia by diarylheptanoids from Curcuma comosa Roxb.
- 241 Downloads
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.
KeywordsApoptosis Catechol Leukemia Curcuma comosa Diarylheptanoid Pro-oxidant
This study was supported by Mahidol University, Center of Excellence on Environmental Health, Toxicology and Management of Toxic Chemical, and the Office of the Higher Education Commission and Mahidol University under the National Research Universities Initiative and Thailand Research Fund (TRF). The authors thank Profs. Prapon Wilairat and Chumpol Pholpramool for their critical reading and comments on the manuscript.
Conflict of interest
- Armstrong JS, Jones DP. Glutathione depletion enforces the mitochondrial permeability transition and causes cell death in HL60 cells that over express Bcl-2. FASEB J. 2002;10:1263–5.Google Scholar
- Boelsterli Urns A. Mechanisms of necrotic and apoptotic cell death. In: Mechanistic toxicology, 2nd edn. New York: CRC Press; 2007; pp. 185–207Google Scholar
- Kagawa TF, Geierstanger BH, Wang AH, Ho PS. Covalent modification of guanine bases in double-stranded DNA: the 1:2-AZ-DNA structure of d(CGCGCG) in the presence of CuCl2. J Biol Chem. 1994;266:20175–84.Google Scholar
- Martin S, Reutelingsperger C, McGahon A, Rader J, van Schie R, LaFace D, et al. Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J Exp Med. 1995;182:1545–56.PubMedCrossRefGoogle Scholar
- Suksamrarn A, Ponglikitmongkol M, Wongkrajang K, Chindaduang A, Kittidanairak S, Jankam A, et al. Diarylheptanoids, new phytoestrogens from the rhizomes of Curcuma comosa: isolation, chemical modification and estrogenic activity evaluation. Bioorg Med Chem. 2008;16:6891–902.PubMedCrossRefGoogle Scholar
- Taraphdar AK, Roy M, Bhattacharya RK. Natural products as inducers of apoptosis: implication for cancer therapy and prevention. Currt Sci. 2001;80:1387–96.Google Scholar