Journal
JOURNAL OF MEDICINAL FOOD
Volume 15, Issue 3, Pages 231-241Publisher
MARY ANN LIEBERT INC
DOI: 10.1089/jmf.2011.1701
Keywords
AKT/mammalian target of rapamycin/ribosomal p70 S6 kinase; apoptosis; guava leaves; prostate cancer
Funding
- Korea Science and Engineering Foundation [2011-0006220]
- Korean Ministry of Education, Science and Technology
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This study was carried out to evaluate the anticancer effects of guava leaf extracts and its fractions. The chemical compositions of the active extracts were also determined. In the present study, we set out to determine whether the anticancer effects of guava leaves are linked with their ability to suppress constitutive AKT/mammalian target of rapamycin (mTOR)/ribosomal p70 S6 kinase (S6K1) and mitogen-activated protein kinase (MAPK) activation pathways in human prostate cancer cells. We found that guava leaf hexane fraction (GHF) was the most potent inducer of cytotoxic and apoptotic effects in PC-3 cells. The molecular mechanism or mechanisms of GHF apoptotic potential were correlated with the suppression of AKT/mTOR/S6K1 and MAPK signaling pathways. This effect of GHF correlated with down-regulation of various proteins that mediate cell proliferation, cell survival, metastasis, and angiogenesis. Analysis of GHF by gas chromatography and gas chromatography-mass spectrometry tentatively identified 60 compounds, including beta-eudesmol (11.98%), alpha-copaene (7.97%), phytol (7.95%), alpha-patchoulene (3.76%), beta-caryophyllene oxide (CPO) (3.63%), caryophylla-3(15), 7(14)-dien-6-ol (2.68%), (E)-methyl isoeugenol (1.90%), a-terpineol (1.76%), and octadecane (1.23%). Besides GHF, CPO, but not phytol, also inhibited the AKT/mTOR/S6K1 signaling pathway and induced apoptosis in prostate cancer cells. Overall, these findings suggest that guava leaves can interfere with multiple signaling cascades linked with tumorigenesis and provide a source of potential therapeutic compounds for both the prevention and treatment of cancer.
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