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从伊朗蝎子中发现新的抗癌蛋白 Leptulipin。

Discovery of Leptulipin, a New Anticancer Protein from theIranian Scorpion, .

机构信息

Department of Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan 3514799422, Iran.

Venom and Biotherapeutics Molecules Laboratory, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran 1316943551, Iran.

出版信息

Molecules. 2022 Mar 22;27(7):2056. doi: 10.3390/molecules27072056.

DOI:10.3390/molecules27072056
PMID:35408455
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9000277/
Abstract

Cancer is one of the leading causes of mortality in the world. Unfortunately, the present anticancer chemotherapeutics display high cytotoxicity. Accordingly, the discovery of new anticancer agents with lower side effects is highly necessitated. This study aimed to discover an anticancer compound from scorpion venom. Bioactivity-guided chromatography was performed to isolate an active compound against colon and breast cancer cell lines. 2D electrophoresis and MALDI-TOF were performed to identify the molecule. A partial protein sequence was obtained by mass spectrometry, while the full-length was deciphered using a cDNA library of the venom gland by bioinformatics analyses and was designated as leptulipin. The gene was cloned in pET-26b, expressed, and purified. The anticancer effect and mechanism action of leptulipin were evaluated by MTT, apoptosis, and cell cycle assays, as well as by gene expression analysis of apoptosis-related genes. The treated cells displayed inhibition of cell proliferation, altered morphology, DNA fragmentation, and cell cycle arrest. Furthermore, the treated cells showed a decrease in expression and an increase in and genes. In this study, we discovered a new anticancer protein from scorpion venom. Leptulipin showed significant anticancer activity against breast and colon cancer cell lines.

摘要

癌症是世界上主要的死亡原因之一。不幸的是，目前的抗癌化疗药物显示出很高的细胞毒性。因此，非常需要发现具有更低副作用的新抗癌药物。本研究旨在从蝎子毒液中发现一种抗癌化合物。采用生物活性导向色谱法分离对结肠和乳腺癌细胞系具有活性的化合物。进行二维电泳和 MALDI-TOF 以鉴定该分子。通过质谱获得部分蛋白质序列，而通过生物信息学分析毒液腺 cDNA 文库来破译全长序列，并将其命名为 leptulipin。该基因被克隆到 pET-26b 中进行表达和纯化。通过 MTT、凋亡和细胞周期分析以及凋亡相关基因的表达分析来评估 leptulipin 的抗癌作用和机制作用。处理过的细胞显示出抑制细胞增殖、形态改变、DNA 片段化和细胞周期停滞。此外，处理过的细胞显示 表达减少， 和 基因增加。在这项研究中，我们从蝎子毒液中发现了一种新的抗癌蛋白。Leptulipin 对乳腺癌和结肠癌细胞系表现出显著的抗癌活性。

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