| Activation of caspases and poly (ADP-ribose) polymerase cleavage to induce apoptosis in leukemia HL-60 cells by Inula racemosa. | |
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MedLine Citation:
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PMID: 20600805 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Inula racemosa Hook.f. commonly known as Pushkarmula (Compositae) has been used as a traditional drug in India, China and Europe. In the present study, 95% ethanolic extract of roots and its fractions (n-hexane, chloroform, n-butanol and aqueous) were evaluated for in vitro cytotoxicity against cancer cell lines of colon, ovary, prostate, lung, CNS and leukemia. The n-hexane fraction containing alantolactone and isoalantolactone as its major constituents was further studied for its mode of action in HL-60 cells. The lowest IC(50) value of n-hexane fraction was 10.25 microg/ml for Colo-205, a colon cancer cell line whereas, 17.86 microg/ml was the highest IC(50) value observed against CNS cancer cell line SF-295. Further studies on HL-60 cells treated with n-hexane fraction at 10, 25 and 50 microg/ml for 6h, revealed that it induces apoptosis through intrinsic as well as extrinsic pathways by generating reactive oxygen species (ROS) intermediates. Mitochondrial dysfunction prompted the release of cytochrome c, translocation of pro-apoptotic protein (Bax), activation of caspase cascade, resulting in the cleavage of some specific substrates for caspase-3 such as poly (ADP-ribose) polymerase (PARP), which eventually leads to apoptosis. The results of present study strongly support further research and development of bioactive constituents from Inula racemosa as potential anticancer agent with possible therapeutic implication. |
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Authors:
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Harish Chandra Pal; Irum Sehar; Shashi Bhushan; Bishan Dutt Gupta; Ajit Kumar Saxena |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-17 |
Journal Detail:
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Title: Toxicology in vitro : an international journal published in association with BIBRA Volume: 24 ISSN: 1879-3177 ISO Abbreviation: Toxicol In Vitro Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-31 Completed Date: 2010-12-14 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8712158 Medline TA: Toxicol In Vitro Country: England |
Other Details:
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Languages: eng Pagination: 1599-609 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Pharmacology Division, Indian Institute of Integrative Medicine, Jammu, J&K, India. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology* Apoptosis / drug effects* Caspases / biosynthesis* Cell Survival / drug effects Chromatography, High Pressure Liquid DNA, Neoplasm / analysis Enzyme Activation / drug effects HL-60 Cells Humans Inhibitory Concentration 50 Inula / chemistry* Leukemia / drug therapy*, metabolism, pathology Membrane Potential, Mitochondrial / drug effects Mitochondria / drug effects Plant Extracts / chemistry, pharmacology* Plant Roots / chemistry Poly(ADP-ribose) Polymerases / metabolism* Reactive Oxygen Species / metabolism Tumor Stem Cell Assay |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/DNA, Neoplasm; 0/Plant Extracts; 0/Reactive Oxygen Species; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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