title: Oleanen induces apoptosis of cervical cancer cells by up-regulation of Bim.
abstract: OBJECTIVE
  Plants belonging to the genus Celastrus exhibit antitumor activity and the ability to reverse multidrug resistance in tumor cells; however, it remains unclear whether the compound oleanen from Celastrus hypoleucus also exhibits antitumor activity. The objective of this study was to explore the inhibitory effect of 12-oleanene-3β, 6α-diol (oleanen) on the proliferation of cervical cancer HeLa cells in vitro, as well as its relative mechanism.
  
  
  METHODS
  HeLa cells were treated with different concentrations of oleanen for different times. Cell proliferation was determined by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide assay. Cell apoptosis was evaluated by flow cytometry and caspases activities assay. The expression of several proapoptotic proteins belonging to the Bcl-2 family, such as Bax, Bim, and Bad, was detected by Western blot.
  
  
  RESULTS
  Oleanen mainly inhibited the proliferation of HeLa cells at the G0 to G1 and G2 to M phases, and the IC50 of oleanen for cells was significantly higher at 24 hours compared to 48 hours (17.45 ± 3.71 vs 9.02 ± 0.83 μg/mL, respectively; P < 0.05). The significant increase in activity of caspase 3/7, caspase 6 in oleanen-treated HeLa cells indicated that oleanen promoted the apoptosis of HeLa cells. The activity of caspase 9 representing the endogenous apoptotic pathways also increased obviously in oleanen treatment. Furthermore, the increase in the expression of Bim was the most significant among the Bcl-2 family after oleanen treatment.
  
  
  CONCLUSIONS
  Oleanen up-regulates the expression of Bim and other proapoptotic molecules to activate the endogenous apoptosis pathway, thus promoting apoptosis and inhibiting proliferation of human cervical cancer HeLa cells in vitro.
authors: Department of Gynecology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors: Ningyue
authors: N
authors: Gan
authors: Gang
authors: G
authors: Chen
authors: Weijiang
authors: W
authors: Zhang
authors: Jianwei
authors: J
authors: Zhou
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D031247:Celastrus; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008565:Membrane Proteins / Q000378:metabolism*; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: C523152:12-oleanene-3beta,6alpha-diol; D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D010936:Plant Extracts; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D009828:Oleanolic Acid; D020169:Caspases