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Growth inhibitory, apoptotic and anti-inflammatory activities displayed by a novel modified triterpenoid, cyano enone of methyl boswellates

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Abstract

Triterpenoids are pentacyclic secondary metabolites present in many terrestrial plants. Natural triterpenoids have been reported to exhibit anti-inflammatory and anti-carcinogenic activities. Here, we show that modifications of ring A of boswellic acid (2 cyano, 3 enone) resulted in a highly active growth inhibitory, anti-inflammatory, pro-differentiative and anti-tumour triterpenoid compound called cyano enone of methyl boswellates (CEMB). This compound showed cytotoxic activity on a number of cancer cell lines with IC50 ranging from 0.2 to 0.6 μM. CEMB inhibits DNA synthesis and induces apoptosis in A549 cell line at 0.25 μM and 1 μM concentrations, respectively. CEMB induces adipogenic differentiation in 3T3-L1 cells at a concentration of 0.1 μM. Finally, administration of CEMB intra-tumourally significantly inhibited the growth of C6 glioma tumour xenograft in immuno-compromised mice. Collectively, these results suggest that CEMB is a very potent anti-tumour compound.

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Abbreviations

AMC:

7-amino-4-methylcoumerin

BrdU:

5-bromo-2′-deoxyuridine

CDDO:

2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid

CEMB:

cyano enone of methyl boswellates

COX-2:

cycloxygenase-2

DAPI:

4′,6-diamidino-2-phenylindole

DMEM:

Dulbucco’s modified eagle’s medium

DMSO:

dimethyl sulphoxide

DPBS:

Dulbucco’s phosphate buffer saline

FBS:

fetal bovine serum

IBMX:

3-isobutyl-methylxanthine

IC50 :

50% inhibitory concentration

IFN IFN-γ:

interferon interferon-γ

iNOS:

induced nitric oxide synthase

MTT:

3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide)

NED:

N-(1-naphthyl) ethyl-enediamine

TGF-β:

transforming growth factor factor-β

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Acknowledgements

We thank Dr Vani Santosh for her help with the histology of tumours. This project was funded by a grant support received from National Institute of Health (NIH)/FIRCA, USA. Infrastructure support received from DST-FIST, UGC-SAP and DBT Program Support, India, are acknowledged. Central Animal Facility at Indian Institute of Science is greatfully acknowledged for the supply of nude mice. Also, we thank the Indian National Science Academy, New Delhi, for the award of honarary scientist position to GSRSR.

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Author notes

  1. Palaniyandi Ravanan

    Present address: Centre for Biomedical Research, School of Biosciences and Technology, Vellore Institute of Technology University, Vellore, 632 014, India

Authors and Affiliations

  1. Department of Molecular Reproduction, Development and Genetics, Bangalore, 560 012, India

    Palaniyandi Ravanan & Paturu Kondaiah

  2. Department of Organic Chemistry, Indian Institute of Science, Bangalore, 560 012, India

    Sanjay K Singh & G S R Subba Rao

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  1. Palaniyandi Ravanan
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  2. Sanjay K Singh
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  3. G S R Subba Rao
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Correspondence to Paturu Kondaiah.

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[Ravanan P, Singh SK, Subba Rao GSR and Kondaiah P 2011 Growth inhibitory, apoptotic and anti-inflammatory activities displayed by a novel modified triterpenoid, cyano enone of methyl boswellates. J. Biosci. 36 XXX–XXX] DOI

Corresponding editor: Seyed E Hasnain

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Ravanan, P., Singh, S.K., Rao, G.S.R.S. et al. Growth inhibitory, apoptotic and anti-inflammatory activities displayed by a novel modified triterpenoid, cyano enone of methyl boswellates. J Biosci 36, 297–307 (2011). https://doi.org/10.1007/s12038-011-9056-7

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