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蝎毒通过调节信号蛋白Erk和STAT3以及在乳腺癌和结肠癌细胞系中造成DNA损伤,导致p53上调以及Bcl-x和BID蛋白表达下调。

Scorpion Venom Causes Upregulation of p53 and Downregulation of Bcl-x and BID Protein Expression by Modulating Signaling Proteins Erk and STAT3, and DNA Damage in Breast and Colorectal Cancer Cell Lines.

作者信息

Al-Asmari Abdulrahman Khazim, Riyasdeen Anvarbatcha, Islam Mozaffarul

机构信息

1 Prince Sultan Military Medical City, Riyadh, Kingdom of Saudi Arabia.

出版信息

Integr Cancer Ther. 2018 Jun;17(2):271-281. doi: 10.1177/1534735417704949. Epub 2017 Apr 25.

Abstract

Scorpion venoms efficiently block the normal neurotransmitter signaling pathway by prejudicing the ion channel operating mechanism in the body system. Besides its negative effect, venoms also possess some beneficial qualities for humans. They have also been shown to exhibit anticancer properties in various cancer types. This unique property of the venom as an anticancer agent is mainly a result of its role in initiating apoptosis and inhibiting several signaling cascade mechanisms that promote cancer cell proliferation and growth. In this study, we examine the effect of venom on phenotypic changes as well as changes at the molecular levels in colorectal and breast cancer cell lines. A dramatic decrease in cell invasion was observed in both cancer cell lines on venom treatment. Additionally, there was decrease in IL-6, RhoC, Erk, and STAT3 in venom-treated cell lines, providing strong evidence of its anticancer properties. Furthermore, decrease in the expression of antiapoptotic proteins and also upregulation of proapoptotic ones by these lines were observed on venom treatment. Moreover, a vivid picture of DNA damage was also detected on venom treatment. In conclusion, scorpion venom possesses significant potential as an anticancer agent against colorectal and breast cancer cell lines.

摘要

蝎毒通过损害人体系统中的离子通道运作机制,有效地阻断正常的神经递质信号通路。除了其负面影响外,蝎毒对人类也具有一些有益特性。它们还被证明在多种癌症类型中具有抗癌特性。蝎毒作为一种抗癌剂的这种独特特性主要是其引发细胞凋亡以及抑制多种促进癌细胞增殖和生长的信号级联机制的结果。在本研究中,我们研究了蝎毒对结肠直肠癌和乳腺癌细胞系表型变化以及分子水平变化的影响。在两种癌细胞系中,经蝎毒处理后均观察到细胞侵袭显著减少。此外,经蝎毒处理的细胞系中白细胞介素 -6、RhoC、细胞外信号调节激酶(Erk)和信号转导子与转录激活子 3(STAT3)均减少,有力地证明了其抗癌特性。此外,经蝎毒处理后,观察到这些细胞系中抗凋亡蛋白表达减少,促凋亡蛋白上调。而且,在蝎毒处理后还检测到明显的DNA损伤迹象。总之,蝎毒作为一种针对结肠直肠癌和乳腺癌细胞系的抗癌剂具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb39/6041906/c9ac020e2430/10.1177_1534735417704949-fig1.jpg

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