title: Water extract of Ashwagandha leaves has anticancer activity: identification of an active component and its mechanism of action.
abstract: BACKGROUND
  Cancer is a leading cause of death accounting for 15-20% of global mortality. Although advancements in diagnostic and therapeutic technologies have improved cancer survival statistics, 75% of the world population live in underdeveloped regions and have poor access to the advanced medical remedies. Natural therapies hence become an alternative choice of treatment. Ashwagandha, a tropical herb used in Indian Ayurvedic medicine, has a long history of its health promoting and therapeutic effects. In the present study, we have investigated an anticancer activity in the water extract of Ashwagandha leaves (ASH-WEX).
  
  
  RESULTS
  Anticancer activity in the water extract of Ashwagandha leaves (ASH-WEX) was detected by in vitro and in vivo assays. Bioactivity-based size fractionation and NMR analysis were performed to identify the active anticancer component(s). Mechanism of anticancer activity in the extract and its purified component was investigated by biochemical assays. We report that the ASH-WEX is cytotoxic to cancer cells selectively, and causes tumor suppression in vivo. Its active anticancer component was identified as triethylene glycol (TEG). Molecular analysis revealed activation of tumor suppressor proteins p53 and pRB by ASH-WEX and TEG in cancer cells. In contrast to the hypophosphorylation of pRB, decrease in cyclin B1 and increase in cyclin D1 in ASH-WEX and TEG-treated cancer cells (undergoing growth arrest), normal cells showed increase in pRB phosphorylation and cyclin B1, and decrease in cyclin D1 (signifying their cell cycle progression). We also found that the MMP-3 and MMP-9 that regulate metastasis were down regulated in ASH-WEX and TEG-treated cancer cells; normal cells remained unaffected.
  
  
  CONCLUSIONS
  We provide the first molecular evidence that the ASH-WEX and TEG have selective cancer cell growth arrest activity and hence may offer natural and economic resources for anticancer medicine.
authors.affiliation: National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Ibaraki, Japan.
authors.forename: Renu
authors.initials: R
authors.lastname: Wadhwa
authors.forename: Rumani
authors.initials: R
authors.lastname: Singh
authors.forename: Ran
authors.initials: R
authors.lastname: Gao
authors.forename: Navjot
authors.initials: N
authors.lastname: Shah
authors.forename: Nashi
authors.initials: N
authors.lastname: Widodo
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nakamoto
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ishida
authors.forename: Keiji
authors.initials: K
authors.lastname: Terao
authors.forename: Sunil C
authors.initials: SC
authors.lastname: Kaul
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D051379:Mice; D010936:Plant Extracts / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D014867:Water / Q000737:chemistry*; D032341:Withania / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D010936:Plant Extracts; D012997:Solvents; D014867:Water; C030693:Ashwagandha