Home | About | Quick Start | FAQ
Beta Version 0.1
DHARA is an online index of articles on Ayurveda published in research journals worldwide. Users Online : 125
  Enter Keyword Below :
      
Advanced

International Journal of Oncology 2007 Oct ; 31 (4) :915-22
The plant alkaloid cryptolepine induces p21WAF1/CIP1 and cell cycle arrest in a human osteosarcoma cell line.

Abstract
We previously established a bioassay method to screen for compounds that activate the promoter activity of p21(WAF1/CIP1), a potent inhibitor of cyclin-dependent kinases, in a p53-independent manner. As an activator of p21(WAF1/CIP1) promoter activity, we isolated cryptolepine (CLP: 5-methyl indolo (2,3b)-quiniine), an indoloquinoline alkaloid, from the traditional Ayurvedic medicinal plant Sida cordifolia. We show here that CLP induces the expression of p21(WAF1/CIP1) with growth arrest in p53-mutated human osteosarcoma MG63 cells. Four micromolar of CLP completely inhibited the growth of MG63 cells and caused G2/M-phase arrest. CLP up-regulated the expression of p21(WAF1/CIP1) at both mRNA and protein levels in a dose-dependent manner. Using several mutant p21(WAF1/CIP1) promoter constructs, we found that the CLP-responsive element is an Sp1 site at -82 relative to the transcription start site of the p21(WAF1/CIP1) promoter. These findings suggest that CLP arrests the growth of MG63 cells by activating the p21(WAF1/CIP1) promoter through the specific Sp1 site in a p53-independent manner. In addition, CLP-mediated cell cycle arrest was reduced by the knockout of the p21(WAF1/CIP1) gene in human colon cancer HCT116 cells, suggesting that the cell cycle arrest by CLP was at least partially mediated through the induction of p21(WAF1/CIP1) expression. Although we need further study of chemotherapeutic effect in vivo, these results raise the possibility that CLP might be a suitable chemotherapeutic agent for treatment of osteosarcoma.

DHARA ID: D003934 Pubmed ID: 17786325


Link To Full Paper

Copyright | Disclaimer | Feedback | Updates | Contact
Developed and maintained by AVP Research Foundation (Formerly AVT Institute for Advanced Research), 136/137, Trichy Road, Ramanathapuram, Coimbatore - 641045, Tamil Nadu, India
Funded by Central Council for Research in Ayurvedic Sciences, Dept. of AYUSH, Ministry of Health and Family Welfare, Government of India, New Delhi