Document Detail

Andrographolide inhibits growth of acute promyelocytic leukaemia cells by inducing retinoic acid receptor-independent cell differentiation and apoptosis.
MedLine Citation:
PMID:  19126299     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: The growth inhibiting potential of andrographolide was evaluated in three acute promyelocytic leukaemia cell line models (HL-60, NB4 and all-trans retinoic acid (ATRA)-resistant NB4-R2). METHODS: In elucidating the mechanisms of growth inhibition, a special emphasis was placed on assessing the induction of differentiation and apoptosis by andrographolide in the primary acute promyelocytic leukaemia NB4 cells. KEY FINDINGS: The compound was 2- and 3-fold more active in inhibiting the growth of HL-60 and NB4-R2 cells compared with NB4 cells, respectively. At IC50 (concentration at which growth of 50% of the cells (compared with medium only treated control cells) is inhibited; 4.5 microM) the compound exhibited strong cell-differentiating activity in NB4 cells, similar to ATRA (IC50 1.5 microM). In the presence of a pure retinoic acid receptor antagonist AGN193109, the growth inhibition of NB4 cells by ATRA was reversed, whereas the activity of andrographolide was not affected. This clearly suggested that andrographolide's cell differentiating activity to induce growth inhibition of NB4 cells most likely occurred via a retinoic acid receptor-independent pathway. At higher concentration (2xIC50), andrographolide was an efficient inducer of apoptosis in NB4 cells. CONCLUSIONS: Taken together, these results suggest andrographolide and its derivatives, apparently with a novel cell differentiating mechanism and with ability to induce apoptosis, might be beneficial in the treatment of primary and ATRA-resistant acute promyelocytic leukaemia.
Shiamala D Manikam; Shiamala T Manikam; Johnson Stanslas
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pharmacy and pharmacology     Volume:  61     ISSN:  0022-3573     ISO Abbreviation:  J. Pharm. Pharmacol.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-07     Completed Date:  2009-03-30     Revised Date:  2009-05-27    
Medline Journal Info:
Nlm Unique ID:  0376363     Medline TA:  J Pharm Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  69-78     Citation Subset:  IM    
Faculty of Medicine and Health Sciences, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
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MeSH Terms
Andrographis / chemistry
Anti-Inflammatory Agents, Non-Steroidal / chemistry,  pharmacology
Antineoplastic Agents / chemistry,  pharmacology
Apoptosis / drug effects*
Cell Differentiation / drug effects*
Cell Line, Tumor
Cell Proliferation / drug effects*
Cell Survival / drug effects
DNA Fragmentation / drug effects
Diterpenes / chemistry,  isolation & purification,  pharmacology*
Dose-Response Relationship, Drug
Drug Resistance, Neoplasm
HL-60 Cells
Inhibitory Concentration 50
Leukemia, Promyelocytic, Acute / metabolism,  pathology
Microscopy, Fluorescence
Molecular Structure
Naphthalenes / chemistry,  pharmacology
Plant Extracts / chemistry,  isolation & purification,  pharmacology
Receptors, Retinoic Acid / antagonists & inhibitors,  physiology*
Tretinoin / chemistry,  pharmacology
Reg. No./Substance:
0/AGN 193109; 0/Anti-Inflammatory Agents, Non-Steroidal; 0/Antineoplastic Agents; 0/Diterpenes; 0/Naphthalenes; 0/Plant Extracts; 0/Receptors, Retinoic Acid; 0/retinoic acid receptor alpha; 302-79-4/Tretinoin; 5508-58-7/andrographolide
Erratum In:
J Pharm Pharmacol. 2009 May;61(5):687
Note: Manikam, Shiamala T [corrected to Manikam, Shiamala T]

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