title: Glycosmis pentaphylla (Retz.) DC arrests cell cycle and induces apoptosis via caspase-3/7 activation in breast cancer cells.
abstract: BACKGROUND
  Glycosmis pentaphylla (Retz.) DC belonging to the family Rutaceae has been traditionally used for the treatment of rheumatism, anaemia, jaundice, skin diseases, bronchitis etc. The plant is traditionally considered as anti-cancer medicine and used by the healers of Bangladesh to treat all types of cancers. Perhaps the key to many of its medicinal applications is its inherent anti-inflammatory property.
  
  
  OBJECTIVE
  The present study is aimed at evaluating the effect of various fractions of G. pentaphylla (Retz.) DC leaves on the cell cycle and apoptosis of breast cancer cells viz. MCF-7 and MDA-MB-231.
  
  
  METHODS
  Various extracts and fractions of the leaves of G. pentaphylla (Retz.) DC were studied for their cytotoxicity with the help of Sulforhodamine B assay, in MCF-7, MDA-MB-231 and Vero cell lines. The most active fractions were studied for their effect on the cell cycle of MCF-7 and MDA-MB-231 cells. Apoptotic studies were done using Hoechst staining, DNA fragmentation, Annexin V staining and caspase-3/7 activation assay in breast cancer cells. HPLC and HPTLC profiling of the active fractions were done.
  
  
  RESULTS
  HPTLC and HPLC profiling revealed the presence of lupeol, chrysin, quercetin, β-sitosterol and kaempferol as components in active fractions. Lupeol and chrysin are being reported in this plant for the first time. The studies showed that the selected fractions possess cell cycle inhibitory and apoptosis inducing effect on both MCF-7 and MDA-MB-231 cells. Apoptotic effect of the fractions on MCF-7 and MDA-MB-231 cells may be through the mitochondrial pathway by the activation of caspase-3/7.
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, Karnataka, India.
authors.forename: M H
authors.initials: MH
authors.lastname: Shoja
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, Karnataka, India.
authors.forename: Neetinkumar D
authors.initials: ND
authors.lastname: Reddy
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, Karnataka, India.
authors.forename: Pawan G
authors.initials: PG
authors.lastname: Nayak
authors.affiliation: Department of Chemistry, Shri Madhwa Vadiraja Institute of Technology and Management, Bantakal, Udupi 574115, Karnataka, India.
authors.forename: K K
authors.initials: KK
authors.lastname: Srinivasan
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, Karnataka, India. Electronic address: mallik.rao@manipal.edu.
authors.forename: C Mallikarjuna
authors.initials: CM
authors.lastname: Rao
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D005419:Flavonoids / Q000032:analysis / Q000494:pharmacology; D006801:Humans; D010636:Phenols / Q000032:analysis / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves; D027821:Rutaceae
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D010636:Phenols; D010936:Plant Extracts; D053148:Caspase 3; D053179:Caspase 7
keywords: Annexin V staining; Apoptosis; Caspase-3/7 activation; Cell cycle arrest; Glycosmis pentaphylla (Retz.) DC; HPLC