Abstract

Context

Lucialdehyde B (LB), an effective triterpenoid isolated from Ganoderma lucidum (Leyss. ex Fr.) Karst. (Polyproraceae), exerts cytotoxic activity against nasopharyngeal carcinoma CNE2 cells.

Objective

To investigate the antiproliferative and pro-apoptotic effects of LB on CNE2 cells and explore its underlying mechanisms.

Materials and methods

LB concentrations of 5–40 μg/mL were used. Cell proliferation was determined using MTT, CFSE, and colony formation assays. LB-induced apoptosis and cell cycle arrest were measured by flow cytometry after 48-h LB treatments. Fluorescence microscopy and flow cytometry were performed to measure the alteration of MMP, mPTP opening, ROS level, and Ca²⁺ content in CNE2 cells. Western blotting was performed to evaluate the expression of mitochondrial apoptosis-related and Ras/ERK signaling proteins.

Results

IC₅₀ values of LB against CNE2 cells for 24, 48, and 72 h were 25.42 ± 0.87, 14.83 ± 0.93, and 11.60 ± 0.77 μg/mL, respectively. The CFSE assay showed that the cell proliferation index was 12.70 in the LB treatment group and 31.44 in the control group. LB significantly reduced clonogenic capacity, promoted cell apoptosis and induced cell cycle arrest at the G2/M phase. Our observations also revealed that LB induced ROS and calcium aggregation, opening of mPTP, MMP reduction, upregulation of mitochondrial apoptosis-related protein expression and inhibition of Ras/ERK signaling cascades.

Discussion

LB suppresses proliferation and induces mitochondrial-dependent apoptosis in nasopharyngeal carcinoma CNE2 cells.

Conclusions

LB may have a potential use as a clinical drug candidate for nasopharyngeal carcinoma treatment.

中文翻译：

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Luci醛 B 抑制鼻咽癌 CNE2 细胞增殖并诱导线粒体依赖性细胞凋亡

摘要

语境

Luci醛 B (LB)，一种从灵芝(Leyss. ex Fr.) 喀斯特中分离出来的有效三萜类化合物。（Polyproraceae）对鼻咽癌 CNE2 细胞具有细胞毒活性。

客观的

探讨LB对CNE2细胞的抗增殖和促凋亡作用并探讨其潜在机制。

材料和方法

使用 5–40 μg/mL 的 LB 浓度。使用 MTT、CFSE 和集落形成测定法测定细胞增殖。LB 处理 48 小时后，通过流式细胞术测量 LB 诱导的细胞凋亡和细胞周期停滞。荧光显微镜和流式细胞仪检测CNE2细胞中MMP、mPTP开放、ROS水平和Ca ^{2+含量的变化。}采用蛋白质印迹法评估线粒体凋亡相关蛋白和 Ras/ERK 信号蛋白的表达。

结果

LB对CNE2细胞24、48和72小时的IC 50 值分别为25.42±0.87、14.83±0.93和11.60±0.77μg/ mL _。CFSE检测显示LB治疗组细胞增殖指数为12.70，对照组细胞增殖指数为31.44。LB显着降低克隆形成能力，促进细胞凋亡并诱导细胞周期停滞在G2/M期。我们的观察还表明，LB 诱导 ROS 和钙聚集、mPTP 开放、MMP 减少、线粒体凋亡相关蛋白表达上调以及 Ras/ERK 信号级联抑制。

讨论

LB 抑制鼻咽癌 CNE2 细胞增殖并诱导线粒体依赖性细胞凋亡。

结论

LB可能具有作为鼻咽癌治疗的临床候选药物的潜在用途。