Naringenin-Induced Apoptotic Cell Death in Prostate Cancer Cells Is Mediated via the PI3K/AKT and MAPK Signaling Pathways
Naringenin-Induced Apoptotic Cell Death in Prostate Cancer Cells Is Mediated via the PI3K/AKT and MAPK Signaling Pathways
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DOI：
10.1002/jcb.25729
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发表时间：
2017-05-01
影响因子：
4
通讯作者：
Song, Gwonhwa
中科院分区：
文献类型：
--
作者：
Lim, Whasun;Park, Sunwoo;Song, Gwonhwa
前列腺癌是男性最常见的癌症，也是男性癌症相关死亡的第二大常见原因。尽管通常使用各种靶向雄激素受体的药物，但患者经常发生疾病复发。为了克服这些限制，人们研究了天然化合物，以寻找它们抑制各种癌细胞进展和转移的证据。在本研究中，我们研究了柚皮素，一种来自柑橘的天然抗氧化类黄酮，对前列腺癌细胞（PC 3和LNCaP）的影响。目前的研究结果与PC 3和LNCaP细胞显示，柚皮素抑制增殖和迁移，同时诱导凋亡和活性氧产生的这些细胞。此外，柚皮素诱导的线粒体膜电位的损失，增加Bax和减少Bcl-2蛋白在PC 3细胞，但不是LNCaP细胞。柚皮素以剂量依赖性方式降低PC 3细胞中ERK 1/2、P70 S6 K、S6和P38的磷酸化，并降低LNCaP细胞中ERK 1/2、P53、P38和JNK蛋白的磷酸化。然而，在PC 3和LNCaP细胞中，柚皮素激活AKT的磷酸化。然后，使用AKT和ERK 1/2细胞信号通路的药理学抑制剂分析与PC 3和LNCaP细胞活力相关的靶向信号蛋白。此外，我们比较了柚皮素和紫杉醇单独和组合的凋亡作用，发现柚皮素增强了紫杉醇抑制前列腺癌细胞系进展的效率。总的来说，这些结果表明，柚皮素是一种潜在的治疗前列腺癌的化学治疗剂。J.细胞。118：1118-1131，2017. (c)2016 Wiley Periodicals，Inc.
Prostate cancer is the most common cancer in men and the second most common cause of cancer-related deaths in men. Although, various drugs targeting the androgen receptor are normally used, the patients frequently undergo recurrence of the disease. To overcome these limitations, natural compounds have been researched for evidence that they suppress progression and metastasis of various cancer cells. In the present study, we investigated effects of naringenin, a natural anti-oxidant flavonoid derived from citrus, on prostate cancer cells (PC3 and LNCaP). Results of present study with PC3 and LNCaP cells revealed that naringenin inhibited proliferation and migration, while inducing apoptosis and ROS production by those cells. In addition, naringenin-induced loss of mitochondrial membrane potential and increased Bax and decreased Bcl-2 proteins in PC3 cells, but not LNCaP cells. In a dose-dependent manner, naringenin decreased phosphorylation of ERK1/2, P70S6K, S6, and P38 in PC3 cells, and reduced phosphorylation of ERK1/2, P53, P38, and JNK proteins in LNCaP cells. However, naringenin activated phosphorylation of AKT in both PC3 and LNCaP cells. Then, targeted signaling proteins associated with viability of PC3 and LNCaP cells were analyzed using pharmacological inhibitors of AKT and ERK1/2 cell signaling pathways. Moreover, we compared the apoptotic effects of naringenin and paclitaxel alone and in combination to find that naringenin enhanced the efficiency of paclitaxel to suppress progression of prostate cancer cell lines. Collectively, these results indicate that naringenin is a potential chemotherapeutic agent for treatment of prostate cancer. J. Cell. Biochem. 118: 1118-1131, 2017. (c) 2016 Wiley Periodicals, Inc.