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Cancer prevention mediated by caffeic acid phenethyl ester involves cyp2b1/2 modulation in hepatocarcinogenesis.

Authors
  • Beltrán-Ramírez, Olga
  • Pérez, Roberto Macías
  • Sierra-Santoyo, Adolfo
  • Villa-Treviño, Saúl
Type
Published Article
Journal
Toxicologic Pathology
Publisher
SAGE Publications
Publication Date
Apr 01, 2012
Volume
40
Issue
3
Pages
466–472
Identifiers
DOI: 10.1177/0192623311431947
PMID: 22291063
Source
Medline
License
Unknown

Abstract

Studies of cancer chemoprevention with caffeic acid phenethyl ester (CAPE) in the resistant hepatocyte model of hepatocarcinogenesis have shown the participation of CYP drug metabolizing enzymes. To prevent neoplastic and preneoplasic lesions, we must specifically identify which CYP activities are modified in the mechanism of action of CAPE. Male Fischer-344 rats were pretreated with CAPE twelve hours before administration of diethylnitrosamine (DEN) and were sacrificed twelve hours after CAPE and twelve hours, twenty-four hours, twenty-four days, and twelve months after DEN. Other rats were treated with the CYP inhibitors α-naphthoflavone or SKF525A and sacrificed twenty-four hours and twenty-four days after DEN. Microsomes were obtained from livers to quantify protein using Western blot. Diethylnitrosamine metabolism was measured based on nitrite formation and liver histology using GGT histochemistry. Caffeic acid phenethyl ester diminished the protein levels of CYP1A2 and CYP2B1/2. The inhibition of CYP2B1/2 prevented the appearance of preneoplastic lesions. Microsomal assays demonstrated that CAPE interfered with DEN activation diminishing nitrites similar to SKF525A and probably mediated by CYP2B1/2 inhibition. A single dose of CAPE before DEN treatment reduced the appearance of tumors by 43%. These results confirmed that CAPE is a promising agent to confer chemoprotection in liver cancer and should be considered for human therapies.

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