title: Molecular mechanism of apoptosis induction in skin cancer cells by the centipedegrass extract.
abstract: BACKGROUND
  Centipedegrass extract (CGE) is mainly composed of maysin and its derivatives, which are recognized internationally as natural compounds. Compared to other flavonoids, maysin has a unique structure in that mannose is bound to the flavonoid backbone. CGE exhibits some biological properties in that it can function as an anti-oxidant, anti-inflammatory, anti-adipogenic, and insecticidal. Whether CGE has other biological functions, such as anti-cancer activity, is unknown.
  
  
  METHODS
  B16F1 (mouse) and SKMEL-5 (human) cells were treated with CGE, and their subsequent survival was determined using MTT assay. We performed a cell cycle analysis using propidium iodide (PI), and detected apoptosis using double staining with annexin V-FITC/PI. In addition, we examined mitochondrial membrane potentials using flow cytometry, as well as signaling mechanisms with an immunoblotting analysis.
  
  
  RESULTS
  CGE inhibited skin cancer cell growth by arresting the cell cycle in the G2/M phase, and increased both early and late apoptotic cell populations without affecting normal cells. Furthermore, we observed mitochondrial transmembrane depolarization, increased cytochrome-c release, caspase-3 and caspase-7 activation, and increased poly ADP-ribose polymerase degradation. CGE also downregulated activation of p-AKT, p-glycogen synthase kinase-3β (GSK-3β), and p-BAD in a time-dependent manner. LY294002 inhibition of phosphoinositide 3-kinase (PI3K) significantly sensitized skin cancer cells, which led to an increase in CGE-induced apoptosis.
  
  
  CONCLUSIONS
  CGE controlled skin cancer cell growth by inhibiting the PI3K/AKT/GSK-3β signaling pathway and activating the effector caspases. This study is the first to demonstrate anti-cancer properties for CGE, and that CGE may be an effective therapeutic agent for treating skin cancer.
authors: Srilatha
authors: S
authors: Badaboina
authors: Hyoung-Woo
authors: HW
authors: Bai
authors: Chul-Hong
authors: CH
authors: Park
authors: Dong Min
authors: DM
authors: Jang
authors: Bo Yun
authors: BY
authors: Choi
authors: Advanced Radiation Technology Institute (ARTI), Korea Atomic Energy Research Institute (KAERI), Jeongeup-si, Jeollabuk-do 580-185, Republic of Korea. bychung@kaeri.re.kr.
authors: Byung Yeoup
authors: BY
authors: Chung
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D006109:Poaceae / Q000737:chemistry*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*
chemical_list: D002867:Chromones; D009025:Morpholines; D010936:Plant Extracts; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D019869:Phosphatidylinositol 3-Kinases; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D020169:Caspases