title: In vitro and in vivo anticancer properties of cucurbitacin isolated from Cayaponia racemosa.
abstract: BACKGROUND
  Cucurbitacins are a group of triterpenoids that have a cucurbitane skeleton with a wide range of biological activities.
  
  
  OBJECTIVE
  This study evaluated the anticancer properties of one cucurbitacin isolated from Cayaponia racemosa Cong. (Cucurbitaceae), 2β,3β,16α,20(R),25-pentahydroxy-22-oxocucurbita-5-en (1), with in vitro and in vivo models.
  
  
  METHODS
  In vitro cytotoxic activity was determined with human leukemia (HL60) and normal blood cells (PBMC). Sarcoma 180 was used as in vivo model.
  
  
  RESULTS
  The cucurbitacin (1) reduced the number of viable cells; however, there was no changed in the number of non-viable cells at 5 µg/mL. Selectivity towards cancer cells was suggested by the absence of activity on normal proliferating lymphocytes at the concentrations tested (IC₅₀ >25 µg/ml). Morphological analysis of compound 1-treated cells showed typical apoptotic features, such as intense deposition of granules in the cytoplasm (eosinophilia), DNA fragmentation and irregularities in the plasma membrane. In addition, the cells treated with compound 1 presented intense vacuolization and disruption of the plasma membrane. Acridine orange/Ethidium bromide staining confirmed these findings, revealing an increased number of apoptotic cells. In the Sarcoma 180 tumor model, compound 1 showed 52 and 62% of antitumor activity, either alone (25 mg/kg/day) or in association with the chemotherapeutic agent 5-FU (10 + 10 mg/kg/day), respectively. Moreover, either alone or associated with 5-FU, treatment with compound 1 caused an increase in spleen weight and morphological alterations related to immunostimulatory properties.
  
  
  CONCLUSIONS
  These data indicate that these naturally occurring compounds have anticancer potential.
authors.affiliation: Departamento de Fisiologia e Farmacologia da Universidade Federal de Pernambuco, Rua prof. Moraes Rego, Cidade Universitária, Recife, PE, Brasil. gcgadelha@yahoo.com.br
authors.forename: Gardenia C G
authors.initials: GC
authors.lastname: Militão
authors.forename: Ivana N F
authors.initials: IN
authors.lastname: Dantas
authors.forename: Paulo Michel P
authors.initials: PM
authors.lastname: Ferreira
authors.forename: Ana Paula N N
authors.initials: AP
authors.lastname: Alves
authors.forename: Davina C
authors.initials: DC
authors.lastname: Chaves
authors.forename: Francisco José Q
authors.initials: FJ
authors.lastname: Monte
authors.forename: Cláudia
authors.initials: C
authors.lastname: Pessoa
authors.forename: Manoel
authors.initials: M
authors.lastname: Odorico de Moraes
authors.forename: Letícia V
authors.initials: LV
authors.lastname: Costa-Lotufo
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019662:Cucurbitaceae / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D051379:Mice; D010946:Plants, Medicinal; D012510:Sarcoma 180 / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D047368:Tumor Burden / Q000187:drug effects; D055815:Young Adult
chemical_list: D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D014315:Triterpenes; D004317:Doxorubicin; D005472:Fluorouracil