title: Effect of parthenolide on growth and apoptosis regulatory genes of human cancer cell lines.
abstract: BACKGROUND
  Parthenolide (a sesquiterpene lactone), a bioactive compound of Tanacetum parthenium (L.) Schultz Bip. (Asteraceae) herb, has been reported for antioxidant and anticancer activities.
  
  
  OBJECTIVE
  The present study evaluated the effect of parthenolide on growth and apoptosis-regulatory genes of human cervical cancer (SiHa) and breast cancer (MCF-7) cell lines.
  
  
  METHODS
  The cytotoxic activity of parthenolide (3.5-21 µM) was examined by MTT and LDH assays at 24 and 48 h time intervals. Apoptotic activity was evaluated by expression analysis of multiple apoptosis-regulatory genes (i.e., p53, Bcl-2, Bax, caspase-3, -6, and -9) by reverse transcriptase-PCR and DNA fragmentation assay.
  
  
  RESULTS
  Parthenolide inhibited the growth of SiHa and MCF-7 cell lines in a concentration-dependent manner at 24 and 48 h time intervals (p < 0.001). The IC50 value of parthenolide against SiHa and MCF-7 cells were 8.42 ± 0.76 and 9.54 ± 0.82 μM, respectively. Parthenolide-treated cells showed up-regulation of p53, Bax, caspase-3, -6, and -3 genes and down-regulation of Bcl-2 gene (p ≤ 0.008). At IC50, the p53 gene was up-regulated by 9.67- and 3.15-fold in SiHa and MCF-7 cells, respectively. The Bax to Bcl-2 ratio was 3.4 and 2.3 for SiHa and MCF-7 cells, respectively. Also, the fragmented genomic DNA in parthenolide-treated cells showed the signs of apoptosis.
  
  
  CONCLUSIONS
  Our study endorsed the biological activity of parthenolide and demonstrated the parthenolide-induced growth inhibition and apoptosis in SiHa and MCF-7 cells by modulating the expression of apoptosis-regulatory genes.
authors.affiliation: Department of Pharmacology, Institute of Pharmacy, NIMS University , Jaipur, Rajasthan , India .
authors.forename: Anees A
authors.initials: AA
authors.lastname: Al-Fatlawi
authors.forename: Atheer A
authors.initials: AA
authors.lastname: Al-Fatlawi
authors.forename: Md
authors.initials: M
authors.lastname: Irshad
authors.lastname: Rahisuddin
authors.forename: Ayaz
authors.initials: A
authors.lastname: Ahmad
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D061986:MCF-7 Cells; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D020903:Tanacetum parthenium / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D012717:Sesquiterpenes; C002669:parthenolide
keywords: Bax; Bcl-2; DNA fragmentation; caspases; cytotoxicity; p53