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Immune modulation and apoptosis induction: Two sides of antitumoural activity of a standardised herbal formulation of Withania somnifera

IR@CSIR-IIIM

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Title Immune modulation and apoptosis induction: Two sides of antitumoural activity of a standardised herbal formulation of Withania somnifera
 
Creator Malik, Fayaz
Kumar, Ajay
Bhushan, Shashi
Mondhe, Dilip M.
Pal, Harish C.
Sharma, Rohit
Khajuria, Anamika
Singh, Surjeet
Singh, Gurdarshan
Saxena, Ajit K.
Suri, Krishan A.
Qazi, Ghulam N.
Singh, Jaswant
 
Subject Biological Sciences
Pharmacological Sciences
 
Description Deregulated apoptosis and suppressed tumour reactive immunity render tumour cells to grow amok in the host body. Traditionally used botanicals may offer potential anticancer
chemo-immunotherapeutic leads.We report in this study a chemically standardised herbal formulation (WSF) of Withania somnifera possessing anticancer and Th1 immune up-regulatory activities. WSF produced cytotoxicity in a panel of human cancer cell lines in vitro.The molecular mechanism of cell cytotoxicity, IC50 48 h �20 lg/ml, was investigated in HL-60, where it induced apoptosis by activating both intrinsic and extrinsic signalling pathways.
It induced early generation of reactive nitrogen and oxygen species (RNOS), thus producing oxidative stress mediated mitochondrial membrane potential (MMP) loss leading to
the release of cytochrome c, the translocation of Bax to mitochondria and apoptosis-inducing factor to the nuclei. These events paralleled the activation of caspase-9, -3 and PARP cleavage. WSF also activated caspase-8 through enhanced expression of TNF-R1 and DR-4, suggesting also the involvement of extrinsic pathway of apoptosis. WSF at 150 mg/kg, i.p., inhibited >50% tumour growth in the mouse tumour models. In tumour-bearing mice,WSF inhibited the expression of pStat-3, with a selective stimulation of Th1 immunity as evidenced by enhanced secretion of IFN-c and IL-2. In parallel, it enhanced the proliferation of CD4+/CD8+ and NK cells along with an increased expression of CD40/CD40L/CD80. In addition, WSF also enhanced T cell activation in camptothecin treated tumour-bearing mice. WSF being safe when given orally up to 1500 mg/kg to rats for 6 months may be found useful in the management of malignancy by targeting at multiple pathways.
 
Date 2009
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://iiim.csircentral.net/262/1/10.1016j.ejca.2009.01.034.pdf
Malik, Fayaz and Kumar, Ajay and Bhushan, Shashi and Mondhe, Dilip M. and Pal, Harish C. and Sharma, Rohit and Khajuria, Anamika and Singh, Surjeet and Singh, Gurdarshan and Saxena, Ajit K. and Suri, Krishan A. and Qazi, Ghulam N. and Singh, Jaswant (2009) Immune modulation and apoptosis induction: Two sides of antitumoural activity of a standardised herbal formulation of Withania somnifera. European Journal of Cancer, 45 (8). pp. 1494-1509. ISSN 09598049
 
Relation http://dx.doi.org/10.1016/j.ejca.2009.01.034
http://iiim.csircentral.net/262/