title: Pivotal Roles of Ginsenoside Rg3 in Tumor Apoptosis Through Regulation of Reactive Oxygen Species.
abstract: Elevated production of reactive oxygen species (ROS) is observed in various cancer types and pathophysiological conditions. In cancer cells, ROS induce cell proliferation, genetic instability, and a malignant phenotype. Ginsenoside Rg3 is the main pharmacologically active component in ginseng and has been reported to have an antioxidant effect. To overcome lung cancer by regulating the ROS level, we investigated the antitumor effect and mechanism of Rg3 and its antioxidative property on Lewis lung carcinoma (LLC) cells.
  
  
  
  Inhibition of ROS was suppressed in LLC cells by Rg3 treatment, and these cells were used to investigate the antioxidant, antiproliferative, and antitumor effects in LLC cells.
  
  
  
  ROS production was increased in cells grown in serum-containing media (conditioned media) compared to those grown in serum-free media. The high level of ROS induced LLC cell proliferation, but treatment with Rg3 (200 ng/ml) resulted in reduction of ROS, leading to inhibition of cell proliferation. Treatment with Rg3 significantly reduced cyclin and cyclin-dependent kinase expression in LLC cells. Additionally, Rg3 treatment significantly suppressed activation of mitogen-activated protein kinases and induced LLC cell apoptosis through activation of pro-apoptotic proteins and suppression of anti-apoptotic proteins.
  
  
  
  Taken together, these findings demonstrate the role of Rg3 in reduction of the intracellular ROS level, attenuation of proliferation via augmentation of cell cycle- and cell proliferation-associated proteins, and activation of apoptosis through regulation of apoptosis-associated proteins in LLC. These findings suggest that Rg3 could be used as a therapeutic agent in lung cancer.
authors.affiliation: Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea.
authors.forename: Hwa Yeon
authors.initials: HY
authors.lastname: Sun
authors.affiliation: Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A.
authors.forename: Jun Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea.
authors.forename: Yong-Seok
authors.initials: YS
authors.lastname: Han
authors.affiliation: Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea.
authors.forename: Yeo Min
authors.initials: YM
authors.lastname: Yoon
authors.affiliation: Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea.
authors.forename: Chul Won
authors.initials: CW
authors.lastname: Yun
authors.affiliation: Department of Urology, Soonchunhyang University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jae Heon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Urology, Soonchunhyang University School of Medicine, Seoul, Republic of Korea.
authors.forename: Yun Seob
authors.initials: YS
authors.lastname: Song
authors.affiliation: Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea Department of Biochemistry, Soonchunhyang University College of Medicine, Cheonan, Republic of Korea ykckss1114@nate.com.
authors.forename: Sang Hun
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D018827:Carcinoma, Lewis Lung / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D017077:Culture Media, Conditioned / Q000737:chemistry; D016895:Culture Media, Serum-Free / Q000737:chemistry; D005434:Flow Cytometry; D036145:Ginsenosides / Q000737:chemistry*; D051379:Mice; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D036145:Ginsenosides; D017382:Reactive Oxygen Species; C097367:ginsenoside Rg3
keywords: Ginsenoside Rg3; Lewis lung carcinoma; anti-tumor effect; apoptosis; reactive oxygen species