A Hexane Fraction of Guava Leaves (Psidium guajava L.) Induces Anticancer Activity by Suppressing AKT/Mammalian Target of Rapamycin/Ribosomal p70 S6 Kinase in Human Prostate Cancer Cells
A Hexane Fraction of Guava Leaves (Psidium guajava L.) Induces Anticancer Activity by Suppressing AKT/Mammalian Target of Rapamycin/Ribosomal p70 S6 Kinase in Human Prostate Cancer Cells
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DOI：
10.1089/jmf.2011.1701
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发表时间：
2012-03-01
影响因子：
2.4
通讯作者：
Ahn, Kwang Seok
中科院分区：
文献类型：
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作者：
Ryu, Nae Hyung;Park, Kyung-Ran;Ahn, Kwang Seok
本研究对番石榴叶提取物及其组分的抗癌作用进行了评价。测定了活性提取物的化学成分。在本研究中，我们开始确定番木瓜叶的抗癌作用是否与它们抑制人类前列腺癌细胞中组成性AKT/哺乳动物雷帕霉素靶蛋白(mTOR)/核糖体p70 S6激酶（S6K1）和丝裂原活化蛋白激酶（MAPK）激活途径的能力有关。我们发现番石榴叶己烷组分（GHF）对PC-3细胞的细胞毒性和凋亡作用最有效。GHF凋亡电位的分子机制或机制与抑制AKT/mTOR/S6K1和MAPK信号通路有关。GHF的这种作用与介导细胞增殖、细胞存活、转移和血管生成的各种蛋白的下调有关。通过气相色谱和气相色谱-质谱联用分析，初步鉴定出60种化合物，包括-桉木酚（11.98%）、-copaene（7.97%）、叶绿醇（7.95%）、-广藿香烯（3.76%）、-石竹烯氧化物（CPO）（3.63%）、石竹烯-3（15）、7(14)-二烯-6-醇（2.68%）、(E)-甲基异丁香酚（1.90%）、-松油醇（1.76%）和十八烷（1.23%）。除GHF外，CPO还能抑制AKT/mTOR/S6K1信号通路，诱导前列腺癌细胞凋亡，而叶绿醇不具有这种作用。总的来说，这些发现表明番石榴叶可以干扰与肿瘤发生有关的多种信号级联反应，并为预防和治疗癌症提供潜在治疗化合物的来源。
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.