Alpha-tomatine induces apoptosis and inhibits nuclear factor-kappa B activation on human prostatic adenocarcinoma PC-3 cells.
Alpha-tomatine induces apoptosis and inhibits nuclear factor-kappa B activation on human prostatic adenocarcinoma PC-3 cells.
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α-呈α-诱导凋亡并抑制人类前列腺腺癌PC-3细胞的核因子-kappa B激活。
DOI：
10.1371/journal.pone.0018915
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发表时间：
2011-04-26
期刊：
影响因子：
3.7
通讯作者：
Mustafa MR
中科院分区：
文献类型：
--
作者：
Lee ST;Wong PF;Cheah SC;Mustafa MR
α-番茄素（α-番茄素）是番茄（lycopersico esculentum）中的主要皂苷。本研究探讨α-番茄素对雄激素不依赖型人前列腺癌PC-3细胞的化学预防作用。α-番茄素对高侵袭性人前列腺癌PC-3细胞的抑制作用呈浓度依赖性，半有效浓度（EC50）为1.67±0.3µM。它对正常人类肝脏WRL-68细胞和正常人类前列腺RWPE-1细胞的细胞毒性也较小。细胞阻抗实时细胞分析仪（RTCA）实时生长动力学检测结果显示，α-番茄素对PC-3细胞早在处理后1小时就表现出细胞毒性作用。α-番茄素对PC-3癌细胞生长的抑制作用主要表现为诱导凋亡，Annexin V染色阳性，线粒体膜电位降低，核凝聚、f -肌动蛋白极化、细胞膜通透性和细胞色素c表达增加。结果还显示α-番茄素诱导caspase-3、-8和-9的活化，提示细胞凋亡途径包括内源性和外源性。此外，核因子κB （NF-κB）核易位被抑制，从而导致处理后细胞核部分的NF-κB/p50和NF-κB/p65与未处理的对照细胞相比显著降低。这些结果进一步揭示了α-番茄素抗增殖作用的分子机制。α-番茄素诱导前列腺癌细胞凋亡，抑制NF-κB活化。这些结果表明α-番茄素可能对预防前列腺癌的发生和发展有益。
Alpha-tomatine (α-tomatine) is the major saponin in tomato (Lycopersicon esculentum). This study investigates the chemopreventive potential of α-tomatine on androgen-independent human prostatic adenocarcinoma PC-3 cells. Treatment of highly aggressive human prostate cancer PC-3 cells with α-tomatine resulted in a concentration-dependent inhibition of cell growth with a half-maximal efficient concentration (EC50) value of 1.67±0.3 µM. It is also less cytotoxic to normal human liver WRL-68 cells and normal human prostate RWPE-1 cells. Assessment of real-time growth kinetics by cell impedance-based Real-Time Cell Analyzer (RTCA) showed that α-tomatine exhibited its cytotoxic effects against PC-3 cells as early as an hour after treatment. The inhibitory effect of α-tomatine on PC-3 cancer cell growth was mainly due to induction of apoptosis as evidenced by positive Annexin V staining and decreased in mitochondrial membrane potential but increased in nuclear condensation, polarization of F-actin, cell membrane permeability and cytochrome c expressions. Results also showed that α-tomatine induced activation of caspase-3, -8 and -9, suggesting that both intrinsic and extrinsic apoptosis pathways are involved. Furthermore, nuclear factor-kappa B (NF-κB) nuclear translocation was inhibited, which in turn resulted in significant decreased in NF-κB/p50 and NF-κB/p65 in the nuclear fraction of the treated cells compared to the control untreated cells. These results provide further insights into the molecular mechanism of the anti-proliferative actions of α-tomatine. α-tomatine induces apoptosis and inhibits NF-κB activation on prostate cancer cells. These results suggest that α-tomatine may be beneficial for protection against prostate cancer development and progression.
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影响因子：
254.7
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通讯作者：
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