title: Anticancer effect of total annonaceous acetogenins on hepatocarcinoma.
abstract: OBJECTIVE
  To confirm the anticancer effect of total annonaceous acetogenins (TAAs) abstracted from Annona squamosa Linn. on human hepatocarcinoma.
  
  
  METHODS
  The inhibitory effect of TAAs was demonstrated in H22-bearing mice. The potency of TAAs was confirmed as its 50% inhibiting concentration (IC50) on Bel-7402 cell under Sulfur Rhodamine B staining. Both underlying mechanisms were explored as cellular apoptosis and cell cycle under flow cytometry. Mitochondrial and recipient apoptotic pathways were differentiated as mitochondrial membrane potential under flow cytometry and caspases activities under fluorescence analysis.
  
  
  RESULTS
  The inhibitory rate of TAAs in mice was 50.98% at 4 mg/kg dose. The IC50 of TAAs on Bel-7402 was 20.06 µg/mL (15.13-26.61µg/mL). Effective mechanisms of TAAs were confirmed as both of arresting cell cycle at G1 phase and inducing apoptosis dose- and time-dependently. Mitochondrial and recipient pathways involved in apoptotic actions of TAAs.
  
  
  CONCLUSIONS
  TAAs is effective for hepatocarcinoma, via inhibiting proliferation and inducing apoptosis.
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100193, China.
authors.forename: Run-mei
authors.initials: RM
authors.lastname: Yang
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100193, China.
authors.forename: Wen-min
authors.initials: WM
authors.lastname: Li
authors.affiliation: Henan Institute of Engineering, Zhengzhou, 451191, China.
authors.forename: Wei-jun
authors.initials: WJ
authors.lastname: Hu
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100193, China.
authors.forename: Wen-hua
authors.initials: WH
authors.lastname: Huang
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100193, China.
authors.forename: Chun-yan
authors.initials: CY
authors.lastname: Zhu
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100193, China.
authors.forename: Jing-guang
authors.initials: JG
authors.lastname: Yu
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100193, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100193, China.
authors.forename: Da-yong
authors.initials: DY
authors.lastname: Cai
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100193, China. gaonann@126.com.
authors.forename: Nan-nan
authors.initials: NN
authors.lastname: Gao
mesh_terms: D054378:Acetogenins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D031041:Annona / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D009928:Organ Specificity / Q000187:drug effects; D013154:Spleen / Q000187:drug effects; D013950:Thymus Gland / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D054378:Acetogenins; D000972:Antineoplastic Agents, Phytogenic; D020169:Caspases
keywords: annonaceous acetogenins; apoptosis; hepatocarcinoma; proliferation