Effect of pH on antitumor activity of Chinese cobra (Naja atra) cytotoxin-XII.

IF 2 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Cytotechnology Pub Date : 2025-02-01 Epub Date: 2024-12-13 DOI:10.1007/s10616-024-00681-8

Xiancai Su, Jiayi Zhou, Mingyuan Zhang, Xiaoping Kang, Dongli Lu, Yanling Chen, Qing Lin, Cailing Yan, Yunlu Xu

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引用次数: 0

Abstract

Cytotoxins (CTXs), proteins found in cobra venom, selectively inhibit tumor cell proliferation. Herein, we selected CTX-XII because of its potent antitumor activity to investigate the effect of solution pH on its response. MTT assay results showed significantly higher inhibition rates for CTX-XII at pH 5.72 (75.79 ± 3.48%) than that at pH 7.32 (50.75 ± 3.8%). Flow cytometry demonstrated that apoptosis rates in B16F10 cells induced by CTX-XII were also higher at pH 5.72 (44.92 ± 7.94%) and 4.12 (42.87 ± 1.89%) than at pH 7.32 (23.5 ± 4.02%). Confocal laser scanning microscopy images showed that red fluorescence, representing CTX-XII concentration, was more intense around tumor cells at pH 5.72, with higher levels in the cytoplasm, than at pH 7.32. In the murine melanoma model, tumor weight in the pH 5.72 CTX-XII group (0.45 ± 0.19 g) was significantly lower than that in the pH 7.32 CTX-XII group (0.84 ± 0.42 g). These results indicate that pH has a strong influence on the antitumor activity of CTX-XII, likely due to pH-dependent ionization changes in CTX-XII that increase its affinity for and penetration into tumor cell membranes. This study provides new insights into the antitumor effects of CTXs and factors influencing their activity.

Supplementary information: The online version contains supplementary material available at 10.1007/s10616-024-00681-8.

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pH 值对眼镜蛇细胞毒素-XII 抗肿瘤活性的影响

细胞毒素（CTXs）是眼镜蛇毒液中的蛋白质，可选择性地抑制肿瘤细胞的增殖。由于 CTX-XII 具有很强的抗肿瘤活性，我们选择了它来研究溶液 pH 值对其反应的影响。MTT 检测结果显示，CTX-XII 在 pH 值为 5.72 时的抑制率（75.79 ± 3.48%）明显高于 pH 值为 7.32 时的抑制率（50.75 ± 3.8%）。流式细胞仪显示，CTX-XII 诱导的 B16F10 细胞凋亡率在 pH 值为 5.72（44.92 ± 7.94%）和 4.12（42.87 ± 1.89%）时也高于 pH 值为 7.32（23.5 ± 4.02%）时。共焦激光扫描显微镜图像显示，pH 值为 5.72 时肿瘤细胞周围的红色荧光（代表 CTX-XII 浓度）比 pH 值为 7.32 时更强，细胞质中的含量更高。在小鼠黑色素瘤模型中，pH 值为 5.72 的 CTX-XII 组肿瘤重量（0.45 ± 0.19 克）明显低于 pH 值为 7.32 的 CTX-XII 组（0.84 ± 0.42 克）。这些结果表明，pH值对CTX-XII的抗肿瘤活性有很大影响，这可能是由于CTX-XII的电离变化依赖于pH值，从而增加了其对肿瘤细胞膜的亲和力和穿透力。这项研究为CTX的抗肿瘤作用以及影响其活性的因素提供了新的见解：在线版本包含补充材料，可查阅 10.1007/s10616-024-00681-8。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cytotechnology 生物-生物工程与应用微生物

CiteScore

4.10

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The scope of the Journal includes: 1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products. 2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools. 3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research. 4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy. 5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.