title: Silibinin inhibits tumor growth through downregulation of extracellular signal-regulated kinase and Akt in vitro and in vivo in human ovarian cancer cells.
abstract: Anticancer activity of silibinin, a flavonoid, has been demonstrated in various cancer cell types. However, the underlying mechanisms were not elucidated in human ovarian cancer cells. The present study was undertaken to examine the effect of silibinin in vitro and in vivo on tumor growth in human ovarian cancer cells. Silibinin decreased cell viability in a dose- and time-dependent manner. Silibinin caused an increase in reactive oxygen species (ROS) generation, and the silibinin-induced cell death was prevented by the antioxidant N-acetylcysteine (NAC). Western blot analysis showed silibinin-induced downregulation of extracellular signal-regulated kinase (ERK) and Akt. Transfection of constitutively active forms of MEK and Akt prevented the silibinin-induced cell death. Oral administration of silibinin in animals with subcutaneous A2780 cells reduced tumor volume. Subsequent tumor tissue analysis showed that silibinin treatment induced a decrease in Ki-67-positive cells, an increase in transferase-mediated dUTP nick end labeling (TUNEL)-positive cells, activation of caspase-3, and inhibition of p-ERK and p-Akt. These results indicate that silibinin reduces tumor growth through inhibition of ERK and Akt in human ovarian cancer cells. These data suggest that silibinin may serve as a potential therapeutic agent for human ovarian cancers.
authors.affiliation: Department of Medicine, Graduate School of Medicine, Pusan National University , Busan 602-739, Korea.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Cho
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Suh
authors.forename: Soo Hyeon
authors.initials: SH
authors.lastname: Moon
authors.forename: Yong Jung
authors.initials: YJ
authors.lastname: Song
authors.forename: Man Soo
authors.initials: MS
authors.lastname: Yoon
authors.forename: Do Yoon
authors.initials: DY
authors.lastname: Park
authors.forename: Kyung Un
authors.initials: KU
authors.lastname: Choi
authors.forename: Yong Keun
authors.initials: YK
authors.lastname: Kim
authors.forename: Ki Hyung
authors.initials: KH
authors.lastname: Kim
mesh_terms: D000111:Acetylcysteine / Q000009:adverse effects; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D019394:Ki-67 Antigen; D017382:Reactive Oxygen Species; D012838:Silymarin; D000077385:Silybin; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D000111:Acetylcysteine