Alantolactone pyrazoline analogue inhibits cancer cell proliferation and induces apoptosis in non-small cell lung carcinoma cells

<p>The aim of the current study was to evaluate the anticancer and apoptotic effects of alantolactone pyrazoline analogue in human non-small cell lung cancer (NCI-H460) cells. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra-zolium bromide) assay was used to evaluate the cell viability while as fluorescence microscopy was used to assess the effect on apoptosis, cellular and nuclear morphology. Flow cytometry evaluated the effect of APA on cell cycle arrest in these cells. The results revealed that APA induced potent, time and dose-dependent cytotoxic effects on the growth of NCI-H460 cells. It also inhibited colony forming tendency as well as cell invasion capability of these cancer cells. APA induced dose-dependent nuclear and cellular morphological effects including chromatin condensation and DNA fragmentation. Flow cytometry revealed that the anticancer effects of APA might be due to its cell cycle arrest inducing tendency in G0/G1 phase of the cell cycle.</p>

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Actinomycin V Suppresses Human Non-Small-Cell Lung Carcinoma A549 Cells by Inducing G2/M Phase Arrest and Apoptosis via the p53-Dependent Pathway

Marine Drugs ◽

10.3390/md17100572 ◽

2019 ◽

Vol 17 (10) ◽

pp. 572 ◽

Cited By ~ 4

Author(s):

Shi-qi Lin ◽

Fu-juan Jia ◽

Cai-yun Zhang ◽

Fang-yuan Liu ◽

Jia-hui Ma ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Lung Carcinoma ◽

Small Cell Lung Carcinoma ◽

A549 Cells ◽

Small Cell ◽

Small Cell Lung ◽

Cell Lung Carcinoma ◽

Cycle Arrest ◽

M Phase

Actinomycin V, extracted and separated from marine-derived actinomycete Streptomyces sp., as the superior potential replacement of actinomycin D (which showed defect for its hepatotoxicity) has revealed an ideal effect in the suppression of migration and invasion in human breast cancer cells as referred to in our previous study. In this study, the involvement of p53 in the cell cycle arrest and pro-apoptotic action of actinomycin V was investigated in human non-small-cell lung carcinoma A549 cells. Results from the 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide assay showed that cytotoxic activity of actinomycin V on A549 cells (with wild-type p53) was stronger than the NCI-H1299 cells (p53-deficient). Actinomycin V upregulated both of the protein and mRNA expression levels of p53, p21Waf1/Cip1 and Bax in A549 cells. For this situation, actinomycin V decreased the M-phase related proteins (Cdc2, Cdc25A and Cyclin B1) expression, arrested cells in G2/M phase and subsequently triggered apoptosis by mediating the Bcl-2 family proteins’ expression (Bax and Bcl-2). Furthermore, the effects of cell cycle arrest and apoptosis in A549 cells which were induced by actinomycin V could be reversed by the pifithrin-α, a specific inhibitor of p53 transcriptional activity. Collectively, our results suggest that actinomycin V causes up-regulation of p53 by which the growth of A549 cells is suppressed for cell cycle arrest and apoptosis.

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