A Hexane Fraction of Guava Leaves (Psidium guajavaL.) Induces Anticancer Activity by Suppressing AKT/Mammalian Target of Rapamycin/Ribosomal p70 S6 Kinase in Human Prostate Cancer Cells

Abstract

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 β-eudesmol (11.98%), α-copaene (7.97%), phytol (7.95%), α-patchoulene (3.76%), β-caryophyllene oxide (CPO) (3.63%), caryophylla-3(15),7(14)-dien-6-ol (2.68%), (E)-methyl isoeugenol (1.90%), α-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.

Phytopharmacological overview of Psidium guajava Linn.

“…Ryu et al 20 identified 60 compounds in a hexane fraction of P. guajava, including β-eudesmol, α-copaene, phytol, α-patchoulene, β-caryophyllene oxide, caryophylla-3(15),7(14)-dien-6-ol, (E)-methyl isoeugenol, α-terpineol, and octadecane. Shao et al 21 isolated and identified clovane-2 beta, 9 alpha-diol, 2 beta-acetoxyclovan-9 alpha-ol, 9 beta-diol, ent-T-muurolol, clov-2-ene-9 alpha-ol, (+)-globulol, (+)-caryolane-1, isophytol, gossypetin, tamarixetin, kaempferol, guajaverin, quercetin, avicularin, chrysin 6-C-glucoside, guavinoside A, guavinoside B 3'-Omethyl-3, 4-methylenedioxyellagic acid 4'-O-beta-D-glucopyranoside and p-hydroxy-benzoic acid.…”

“…It suppresses the AKT/mammalian target of rapamycin/ribosomal p70 S6 kinase and mitogen-activated protein kinase signaling pathways and this correlated with down-regulation of various proteins that mediate cell proliferation, cell survival, metastasis, as well as angiogenesis. 20 The P. guajava extract exerted anticancer activity on haematological and solid neoplasias. P. guajava and its pulp ex-tract are found to induce the apoptosis, which accompanied by caspase activation and p16, p21, Fas ligand, Bcl-2-associated agonist of cell death as well as TNF receptor super-family, member 10b, over expression.…”

Chemical composition, antioxidant, antitumor, anticancer and cytotoxic effects ofPsidium guajavaleaf extracts

“…Even though some earlier studies are reported on the use of P. guajava for the treatment of cancer (Sulain et al 2012;Ryu et al 2012), no such comprehensive study on different solvent extracts of P. guajava leaves native to Fresh leaves of P. guajava were rinsed with distilled water to remove dust and any particulate matter. Leaves were spread separately on paper sheets in a well-ventilated room.…”

Effect of Guava (Psidium guajava) Leaves Essential Oil on Some Reproductive Parameters in Male Guinea Pig (Cavia porcellus)

“…[3][4][5]. Studies on extracts from the leaves of P. guajava and essential oil they contain showed that they possess anti-inflammatory, antibiotics, analgesics, hepato protective and antioxidant activities [6][7][8].…”