Crocus Sativus Stigma Extract and Its Major Constituent Crocin Possess Significant Antiproliferative Properties Against Human Prostate Cancer

Crocus Sativus Stigma Extract and Its Major Constituent Crocin Possess Significant Antiproliferative Properties Against Human Prostate Cancer
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DOI:
10.1080/01635581.2013.767368
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发表时间:
2013-08-01
影响因子:
2.9
通讯作者:
Festuccia, Claudio
Festuccia, Claudio
中科院分区:
医学4区
文献类型:
--
作者:
D'Alessandro, Anna M.;Mancini, Andrea;Festuccia, Claudio

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在本研究中,我们研究了藏红花提取物(SE)及其主要成分藏红花素对5种不同的恶性和2种非恶性前列腺癌细胞系的抗增殖作用。采用高效液相色谱法测定藏红花素的纯度和含量。用不同浓度的SE或藏红花素孵育48h。同时观察细胞周期和凋亡情况。SE和藏红花素在所有恶性细胞系中均具有时间和浓度依赖性,其IC50值在0.4 ~ 4mg/ml之间,而藏红花素的IC50值在0.26 ~ 0.95mM/ml之间。非恶性细胞未受影响。流式细胞术显示,大多数细胞停留在G(0)/G(1)期,凋亡细胞显著存在。Western blot分析显示,Bcl-2的表达明显下调,而Bax的表达明显上调。caspase活性分析表明,caspase依赖途径参与caspase-9的激活,提示其内在途径。综上所述,SE和藏红花素均能抑制前列腺癌细胞增殖,阻滞细胞周期进程,诱导细胞凋亡。因此,这些药物可以潜在地用作前列腺癌管理的化学预防剂和化学治疗剂。
In this study, we investigated the antiproliferative effects of saffron extract (SE) and its major constituent crocin on 5 different malignant and 2 nonmalignant prostate cancer cell lines. Using high performance liquid chromatography (HPLC), the purity and content of crocin were determined. All cells were incubated with different concentrations of SE or crocin for 48h. Cell cycle and apoptosis were also evaluated. In a time- and concentration-dependent manner, both SE and crocin reduced cell proliferation in all malignant cell lines with IC50 values ranging between 0.4 and 4mg/ml for SE and between 0.26 and 0.95mM/ml for crocin. Nonmalignant cells were not affected. Flow cytometry profiles revealed that most cells were arrested at G(0)/G(1) phase with a significant presence of apoptotic cells. Western blot analysis revealed that the expression of Bcl-2 was strikingly downregulated, whereas Bax was upregulated. Analysis of caspase activity indicated a caspase-dependent pathway with involvement of caspase-9 activation, suggesting an intrinsic pathway. Based on these findings, it can be concluded that both SE and crocin can inhibit cell proliferation, arrest cell cycle progression, inducing apoptosis in prostate cancer. Consequently, these agents could potentially be used as a chemopreventive as well as a chemotherapeutic agent for prostate cancer management.