Mahanimbine Exerts Anticancer Effects on Human Pancreatic Cancer Cells by Triggering Cell Cycle Arrest, Apoptosis, and Modulation of AKT/Mammalian Target of Rapamycin (mTOR) and Signal Transducer and Activator of Transcription 3 (STAT3) Signalling Pathways

Pei, Chenlin; He, Qun; Liang, Shuai; Gong, Xuejun

doi:10.12659/msm.911013

Cited by 22 publications

(15 citation statements)

References 18 publications

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“…Mukonal treatment also arrested CNE1 cells in the G2/M phase in a dose-dependent manner. These findings are supported by the findings from studies on similar molecules, such as mahanimbine, which has been reported to trigger cell cycle arrest [19]. The results of the present study suggest that further studies, including in vitro and in vivo studies, and controlled clinical studies, are required to evaluate the potential role of mukonal in the management of nasopharyngeal cancer.…”

Section: Discussionsupporting

confidence: 88%

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

Guo

Guan

et al. 2019

Med Sci Monit

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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.

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Section: Discussionsupporting

confidence: 88%

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

Guo

Guan

et al. 2019

Med Sci Monit

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“…Therefore, in the present study, the effect of murrayanine on the distribution of the cell cycle phase of the A549 cells showed that murrayanine blocked the A549 cells in the G2/M phase of the cell cycle, which was supported by reduced expression levels of cyclin B and cyclin E and upregulation of p21 and p27, which are key the regulators of cell cycle [16]. Apart from cell cycle arrest, apoptosis is a mechanism to eliminate cancer cells [15] and in this study, murrayanine was found to induce apoptosis of the A549 cells. Murrayanine also enhanced the cleavage of caspase-3 and caspase-9 and increased the Bax/Bcl-2 ratio.…”

Section: Discussionmentioning

confidence: 85%

“…Carbazole alkaloids have also been reported to inhibit the growth of cancer cells by triggering cell cycle arrest. Mahanimbine has been reported to halt the growth of pancreatic cancer cells by causing G0/G1 arrest [ 15 ]. Therefore, in the present study, the effect of murrayanine on the distribution of the cell cycle phase of the A549 cells showed that murrayanine blocked the A549 cells in the G2/M phase of the cell cycle, which was supported by reduced expression levels of cyclin B and cyclin E and upregulation of p21 and p27, which are key the regulators of cell cycle [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Murrayanine Induces Cell Cycle Arrest, Oxidative Stress, and Inhibition of Phosphorylated p38 Expression in A549 Lung Adenocarcinoma Cells

Zhang

Gao

et al. 2019

Med Sci Monit

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BackgroundMurrayanine is a carbazole alkaloid derived from Murraya koenigii, which has been used in traditional Chinese medicine in the treatment of cancer. This study aimed to investigate the effects of murrayanine on human lung adenocarcinoma cells in vitro and to investigate the mechanisms of its action.Material/MethodsA549 human lung adenocarcinoma cells and MRC-5 human lung fibroblasts were grown in culture, and an MTT assay determined cell viability. Cells were treated for 24 h with increasing doses of murrayanine (0, 9, 18, and 36 μM). Fluorescence, using 4′, 6-diamidino-2-phenylindole (DAPI), acridine orange, ethidium bromide, and propidium iodide (PI), were used for the detection of apoptosis. The cell cycle was studied with fluorescence-activated cell sorting (FACS), and Western blot evaluated protein expression.ResultsMurrayanine treatment resulted in significant dose-dependent inhibition of the growth of A549 cells (p<0.05), with an IC50 of 9 μM, and arrested the cells at the G2/M phase of the cell cycle, reduced the expression of cyclin D and E, CDK2, 4, and 6, and increased the expression of p21 and p27. Murrayanine treatment increased apoptosis of the A549 cells and increased cleaved of caspase-3 and caspase-9, and the Bax/Bcl-2 ratio. Murrayanine treatment increased levels of reactive oxygen species (ROS), disrupted the mitochondrial membrane potential, inhibited invasion, and inhibited phosphorylation of p38 mitogen-activated protein kinase (MAPK) of the A549 cells.ConclusionsMurrayanine induced cell cycle arrest, oxidative stress, and inhibited the expression of phosphorylated p38 in A549 adenocarcinoma cells.

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“…These results established the potential of M. koenigii as an anticancer agent in vitro [11]. Additional evidence for the anticancer activity of M. koenigii has been obtained from rodent cancer cell lines, as well as different in vivo cancer models [12][13][14][22][23][24]114,115]. In an early study, histopathological evidence showed that M. koenigii extract treatment generated a decline in neoplasms in the colon [85].…”

Section: Anticancer Activity (In Vivo and In Vitro)mentioning

confidence: 65%

Medicinal Profile, Phytochemistry, and Pharmacological Activities of Murraya koenigii and its Primary Bioactive Compounds

Balakrishnan

Vijayraja²,

et al. 2020

Antioxidants

105

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The discovery of several revitalizing molecules that can stop or reduce the pathology of a wide range of diseases will be considered a major breakthrough of the present time. Available synthetic compounds may provoke side effects and health issues, which heightens the need for molecules from plants and other natural resources under discovery as potential methods of replacing synthetic compounds. In traditional medicinal therapies, several plant extracts and phytochemicals have been reported to impart remedial effects as better alternatives. Murraya koenigii (M. koenigii) belongs to the Rutaceae family, which is commonly used as a medicinally important herb of Indian origin in the Ayurvedic system of medicine. Previous reports have demonstrated that the leaves, roots, and bark of this plant are rich sources of carbazole alkaloids, which produce potent biological activities and pharmacological effects. These include antioxidant, antidiabetic, anti-inflammatory, antitumor, and neuroprotective activities. The present review provides insight into the major components of M. koenigii and their pharmacological activities against different pathological conditions. The review also emphasizes the need for more research on the molecular basis of such activity in various cellular and animal models to validate the efficacy of M. koenigii and its derivatives as potent therapeutic agents.

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Mahanimbine Exerts Anticancer Effects on Human Pancreatic Cancer Cells by Triggering Cell Cycle Arrest, Apoptosis, and Modulation of AKT/Mammalian Target of Rapamycin (mTOR) and Signal Transducer and Activator of Transcription 3 (STAT3) Signalling Pathways

Cited by 22 publications

References 18 publications

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

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

Murrayanine Induces Cell Cycle Arrest, Oxidative Stress, and Inhibition of Phosphorylated p38 Expression in A549 Lung Adenocarcinoma Cells

Medicinal Profile, Phytochemistry, and Pharmacological Activities of Murraya koenigii and its Primary Bioactive Compounds

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