Mukonal Inhibits Cell Proliferation, Alters Mitochondrial Membrane Potential and Induces Apoptosis and Autophagy in Human CNE1 Nasopharyngeal Carcinoma Cells

Abstract

Departmental sources Background: Nasopharyngeal carcinoma results in high patient morbidity and mortality, due to early metastasis, and toxicity due to chemotherapy. Mukonal is plant-derived carbazole alkaloid that has been used in traditional Chinese medicine to treat several types of cancer. This study aimed to investigate the effects of mukonal on cell proliferation, apoptosis, autophagy, and the mitochondrial membrane potential of nasopharyngeal carcinoma cells in vitro. Material/Methods: CNE1 human nasopharyngeal carcinoma cells and NP69 normal nasopharyngeal epithelial cells were cultured with and without treatment with increasing doses of mukonal. Cell viability was determined by the MTT assay. Fluorescence microscopy was used to detect reactive oxygen species (ROS), mitochondrial membrane potential, and the release of cytochrome C. Flow cytometry was used to examine changes in the cell cycle, electron microscopy examined cell autophagy, and Western blot was performed to measure levels of proteins associated with autophagy and apoptosis. Results: Mukonal had an antiproliferative effect on CNE1 cells, with an IC 50 of 9 µM and there were effects of toxicity on normal NP69 cells. Mukonal triggered ROS-mediated changes in mitochondrial membrane potential which was also accompanied by the discharge of cytochrome C in the CNE1 cells. Mukonal activated autophagy and apoptosis in CNE1 cells, which was also associated with upregulation of the autophagy-related proteins, LC3 II and beclin-1, as well as apoptosis-associated proteins, Bax, cleaved caspase-3 and-9. Mukonal treatment also resulted in CNE1 cells cycle arrest at G 2 /M. Conclusions: Mukonal inhibited the growth of human CNE1 nasopharyngeal carcinoma cells in vitro.

Histone demethylase KDM4A plays an oncogenic role in nasopharyngeal carcinoma by promoting cell migration and invasion

“…NPC is considered a rare cancer in most parts of the world, but it has high morbidity and mortality rates due to its early metastasis and chemotherapy toxicity 21 , 22 . Radiation therapy is the main treatment for NPC, but radiation resistance can prevent effective treatment 23 .…”

Mukonal exerts anticancer effects on the human breast cancer cells by inducing autophagy and apoptosis and inhibits the tumor growth in vivo

“…Mukonal is a carbazole alkaloid and has revealed to possess remarkable pharmacological and biological propensities. It has been reported to induce anticancer effects against different human cancer cell lines (Li et al 2018 ; Guo et al 2019 ). Therefore, the current study was undertaken due to accumulative evidences suggesting that mukonal has a great propensity to act as an anticancer agent.…”

“…Mukonal has been reported to show anticancer activities against different human cancer cell lines in vitro including laryngeal AMC-HN-8 cancer cells and nasopharyngeal CNE-1 carcinoma cells. It has shown a remarkable potential of autophagy initiation, apoptosis induction, modification of mitochondrial membrane potential, cell cycle arrest, blocking of MEK/ERK and PI3K/AKT signalling pathways (Li et al 2018 ; Guo et al 2019 ). Therefore, current investigation was designed to unveil the anti-breast cancer potential of mukonal along with its effects of autophagy and apoptosis induction.…”

The anticancer activity of carbazole alkaloids

“…Mukonal (Figure 4 and Table 3; 20, IC 50 : 7.5 µM, MTT assay), an active member of carbazole alkaloids isolated from Murraya koenigii, had the potential to induce antiproliferative effects against MDA-MB-231 and SK-BR-3 cells and no significant toxicity (IC 50 : 110 µM) of mukonal was observed in case of normal MB-157 breast cells. [57,58] 7-Methoxymukonal (21, IC 50 : 82.6 µM, MTT assay), isolated from the root bark of Clausena harmandiana, showed moderate activity against HepG2 cells. [59] The mechanistic studies illustrated that cancer cells.…”