Coptisine-induced cell cycle arrest at G2/M phase and reactive oxygen species–dependent mitochondria-mediated apoptosis in non-small-cell lung cancer A549 cells

Abstract

This study aimed to explore the effect of coptisine on non-small-cell lung cancer and its mechanism through various in vitro cellular models (A549). Results claimed significant inhibition of proliferation by coptisine against A549, H460, and H2170 cells with IC 50 values of 18.09, 29.50, and 21.60 µM, respectively. Also, coptisine exhibited upregulation of pH2AX, cell cycle arrest at G2/M phase, and downregulation of the expression of cyclin B1, cdc2, and cdc25C and upregulation of p21 dose dependently. Furthermore, induction of apoptosis in A549 cells by coptisine was characterized by the activation of caspase 9, caspase 8, and caspase 3, and cleavage of poly adenosine diphosphate ribose polymerase. In addition, coptisine was found to increase reactive oxygen species generation, upregulate Bax/Bcl-2 ratio, disrupt mitochondrial membrane potential, and cause cytochrome c release into the cytosol. Besides, treatment with a reactive oxygen species inhibitor (N-acetyl cysteine) abrogated coptisine-induced growth inhibition, apoptosis, reactive oxygen species generation, and mitochondrial dysfunction. Thus, the mediation of reactive oxygen species in the apoptosisinduced effect of coptisine in A549 cells was corroborated. These findings have offered new insights into the effect and mechanisms of action of coptisine against non-small-cell lung cancer.

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“…Besides, coptisine (12.5‐50 μmol/L, 48 hours) not only promoted DNA damage of A594 cell through increase pH2AX protein (DNA damage marker) level but also triggered the occurrence of apoptosis by up‐regulating ROS, caspase‐3/‐9, Bax/Bcl‐2 and PARP cleavage . Consistent with that in A549 cell, coptisine (2.5‐40 μmol/L, 4 hours; 25‐50 μmol/L, 24 hours) as well modulate ROS caspase‐3/‐9 and Bax/Bcl‐2 in H2O2‐stimulated EA.hy926 and NCI⁃H1650 cells …”

“…31,32 Similar anti-cancer property of coptisine was observed in liver 33,34 In the next study, authors revealed that coptisine and NCI•H1650 cells. [38][39][40] Several studies have established that coptisine exerts ameliorative effect on cancer in in vivo model. Cao Another study, which was aimed to investigate the effect of coptisine on liver cancer-associated acute liver failure, verified that coptisine (37.5-150 mg/kg, oral, once daily for 7 days) down-regulated TLR-4 expressions and apoptotic protein level.…”

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“…Many anti-cancer agents reduce malignant growth by arresting the cell cycle at the G1/S or G2/M phases [ 53 ]. According to previous studies, cell cycle arrest, particularly G2/M phase, might be a useful therapy to prevent the proliferation of cancer cells [ 54 ]. The CDK1, Cyclin B and Cdc25C are essential for inducing G2/M cycle phase, which could enhance the dividing of a cell into two [ 55 ].…”

Hyaluronic acid-functionalized bismuth oxide nanoparticles for computed tomography imaging-guided radiotherapy of tumor

“…As analyzed by flow cytometry (Figures 9A and S8), radiation (6 Gy) alone slightly caused 19.87% of G2/M phase arrest, which might induce apoptosis of cells. 49,50 In addition, HABi 2 O 3 NPs (from 0 to 200 μg/mL) activated apoptotic cell death from 0.446% to 2.34%, as reflected by the sub-G1 proportions. 51 However, the combination of HA-Bi 2 O 3 NPs and radiation dose-dependently increased the extent of G2/M phase arrest and cell apoptosis.…”