title: Furanodiene, a natural product, inhibits breast cancer growth both in vitro and in vivo.
abstract: OBJECTIVE
  Previous studies have reported that the Curcuma wenyujin Y.H. Chen et C. Ling extract, which has a high furanodiene content, showed anti-cancer effects in breast cancer cells in vitro. The present study was designed to evaluate the in vitro and in vivo anti-cancer activity of furanodiene.
  
  
  METHODS
  The in vitro effects of furanodiene were examined on two human breast cancer cell lines, MCF-7 and MDA-MB-231 cells. Assays of proliferation, LDH release, mitochondrial membrane potential (ΔΨm), cell cycle distribution, apoptosis and relevant signaling pathways were performed. The in vivo effect was determined with MCF7 tumor xenograft model in nude mice.
  
  
  RESULTS
  Furanodiene significantly inhibited the proliferation and increased the LDH release in both cell lines in a dose-dependent manner. ΔΨm depolarization, chromatin condensation, and DNA fragmentation were also observed after furanodiene treatment. Furanodiene dose-dependently induced cell cycle arrest at the G0/G1 phase. The protein expressions of p-cyclin D1, total cyclin D1, p-CDK2, total CDK2, p-Rb, total Rb, Bcl-xL, and Akt were significantly inhibited by furanodiene, whereas the protein expressions of Bad and Bax, and the proteolytic cleavage of caspase-9, caspase-7, and poly-ADP-ribose polymerase (PARP) were dramatically increased. Furthermore, the z-VAD-fmk markedly reversed the furanodiene-induced cell cytotoxicity, the proteolytic cleavage of caspase-9, and DNA fragmentation but did not affect the proteolytic cleavage of PARP, whereas the Akt inhibitor VIII increased the furanodiene-induced cytotoxicity and PARP cleavage. In addition, furanodiene dose-dependently suppressed the tumor growth in vivo, achieving 32% and 54% inhibition rates after intraperitoneal injection of 15 mg/kg and 30 mg/kg, respectively.
  
  
  CONCLUSIONS
  Taken together, we concluded that furanodiene suppresses breast cancer cell growth both in vitro and in vivo and could be a new lead compound for breast cancer chemotherapy.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macau, China.
authors.forename: Zhangfeng
authors.initials: Z
authors.lastname: Zhong
authors.forename: Yuanye
authors.initials: Y
authors.lastname: Dang
authors.forename: Xia
authors.initials: X
authors.lastname: Yuan
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Yingbo
authors.initials: Y
authors.lastname: Li
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
authors.forename: Jingrong
authors.initials: J
authors.lastname: Cui
authors.forename: Jinjian
authors.initials: J
authors.lastname: Lu
authors.forename: Qingwen
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xiuping
authors.initials: X
authors.lastname: Chen
authors.forename: Yitao
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053179:Caspase 7 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D030024:Curcuma / Q000737:chemistry; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D005663:Furans / Q000627:therapeutic use* / Q000633:toxicity; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006574:Heterocyclic Compounds, 2-Ring / Q000627:therapeutic use* / Q000633:toxicity; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D014183:Transplantation, Heterologous; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; D006574:Heterocyclic Compounds, 2-Ring; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C442489:furanodiene; D007770:L-Lactate Dehydrogenase; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D053179:Caspase 7; D053453:Caspase 9