Lucialdehyde B suppresses proliferation and induces mitochondria-dependent apoptosis in nasopharyngeal carcinoma CNE2 cells

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.

Keywords:

• Ganoderma lucidum
• triterpenoid
• apoptosis
• cell proliferation

Author contributions

Peng Li conceived and designed the study. Lingxue Liu and Zhangning Yu performed the experiments. Lingxue Liu, Peng Li, and Benchen Liu wrote the manuscript. Jing Chen analyzed the data. Changhui Wu collected the samples. Jianhua Xu and Ye Li coordinated technical support.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Medical Innovation Program of Fujian Provincial Health Commission of China [2017-CX-37] and the National Nature Science Foundation of China [81202560]. The authors appreciate Junjin Lin of Public Technology Service Center of Fujian Medical University for his support in flow cytometric analysis.