Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, People's Republic of China.
Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, People's Republic of China.
Appl Microbiol Biotechnol. 2020 Dec;104(23):10165-10179. doi: 10.1007/s00253-020-10918-z. Epub 2020 Oct 12.
Due to the high mortality rate and an increase in breast cancer incidence, it has been challenging for researchers to come across an effective chemotherapeutic strategy with minimum side effects. Therefore, the need for the development of effective chemotherapeutic drugs is still on the verge. Consequently, we approached a new mechanism to address this issue. The naturally available peptide named latcripin-7A (LP-7A), extracted from a mushroom called Lentinula edodes, provided us promising results in terms of growth arrest, apoptosis, and autophagy in breast cancer cells (MCF-7 and MDA-MB-231). Expressions of protein markers for apoptosis, autophagy, and cell cycle were confirmed via Western blot analysis. Migration and invasion assays were performed to analyze the anti-migratory and anti-invasive properties of LP-7A, while cell cycle analysis was performed via flow cytometry to evaluate its affect over cell growth. Supportive assays were performed like acridine orange, Hoechst 33258 stain, DNA fragmentation, and mitochondrial membrane potential (MMP) to further confirm the anticancer effect of LP-7A on breast cancer cell lines. It is concluded that LP-7A effectively reduces migration and promotes apoptosis as well as autophagy in MCF-7 and MDA-MB-231 breast cancer cell lines by inducing cell growth arrest at G/G phase and decreasing mitochondrial membrane potential without adverse effects on MCF-10A normal breast cells. KEY POINTS: • In this study, we have investigated the anti-cancer activity of novel latcripin-7A (LP-7A), a protein extracted as a result of de novo characterization of Lentinula edodes C • We conclude in our research work that LP-7A can initiate diverse cell death-related events, i.e., apoptosis and autophagy in both triple-positive and triple-negative breast cancer cell lines by interacting with different nodes of cellular signaling that can further be investigated in vivo to gain a better understanding.
由于高死亡率和乳腺癌发病率的增加，研究人员很难找到一种副作用最小的有效化疗策略。因此，开发有效化疗药物的需求仍然迫在眉睫。因此，我们采用了一种新的机制来解决这个问题。从一种名为香菇（Lentinula edodes）的蘑菇中提取的天然存在的肽，名为 latcripin-7A（LP-7A），在乳腺癌细胞（MCF-7 和 MDA-MB-231）的生长抑制、凋亡和自噬方面为我们提供了有希望的结果。通过 Western blot 分析证实了凋亡、自噬和细胞周期的蛋白标志物的表达。进行迁移和侵袭测定以分析 LP-7A 的抗迁移和抗侵袭特性，而通过流式细胞术进行细胞周期分析以评估其对细胞生长的影响。进行支持性测定，如吖啶橙、Hoechst 33258 染色、DNA 片段化和线粒体膜电位（MMP），以进一步证实 LP-7A 对乳腺癌细胞系的抗癌作用。研究结果表明，LP-7A 通过诱导细胞生长停滞在 G0/G1 期和降低线粒体膜电位，有效减少 MCF-7 和 MDA-MB-231 乳腺癌细胞系的迁移并促进细胞凋亡和自噬，而对 MCF-10A 正常乳腺细胞没有不良影响。关键点：• 在这项研究中，我们研究了新型 latcripin-7A（LP-7A）的抗癌活性，LP-7A 是从香菇 C 的从头鉴定中提取的一种蛋白质。• 在我们的研究工作中，我们得出结论，LP-7A 通过与不同的细胞信号节点相互作用，可以在三阳性和三阴性乳腺癌细胞系中引发多种与细胞死亡相关的事件，即凋亡和自噬，这些事件可以进一步在体内进行研究，以获得更好的理解。
