JS‑K induces G2/M phase cell cycle arrest and apoptosis in A549 and H460 cells via the p53/p21WAF1/CIP1 and p27KIP1 pathways

Song, Zeqing; Yin, Yuexin; Hao, Siyuan; Wei, Jianmao; Liu, Bin; Huang, Xiaojie; Gao, Chenfeng; Zhu, Runzhi; Liao, Weiguo; Cai, De

doi:10.3892/or.2019.7104

Cited by 7 publications

(6 citation statements)

References 45 publications

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“…In addition, cell % was markedly reduced from 88.79% to 31.22% at G0/G1 phase when A549 cells were treated with C8. Obtained results suggested that C8 demonstrated a significant antineoplastic effect and led to the stoppage A549 cell cycle progression at G2/M, metaphase, after the gestation period of 24 h. These results were in accordance with the other recent research conducted on A549 cells, wherein the anticancer effects were attributed to the blocking of the G2/M phase [54][55][56].…”

Section: Cell Cycle Analysissupporting

confidence: 89%

Anticancer Activity of Anti-Tubercular Compound(s) Designed on Pyrrolyl Benzohydrazine Scaffolds: A Repurposing Study

et al. 2023

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The present study explored anti-tubercular pyrrole derivatives against cancer targets using different in silico and in vitro approaches. Initially, nineteen anti-tubercular pyrrolyl benzohydrazide derivatives were screened against a potent cancer target PLK1 using an AutoDock Vina approach. Out of the nineteen derivatives, the two most potent derivatives C8 [N′-(4-(1H-pyrrol-1-yl) benzoyl)-3-chlorobenzohydrazide] and C18 [N′-(4-(1H-pyrrol-1-yl) benzoyl)-4-nitrobenzohydrazide], were subjected to molecular simulation analysis for a 100 ns trajectory. Further, these two derivatives were tested against A549, MCF-7, and HepG2 cell lines using an MTT proliferation assay. Apoptotic cell cycle and DAPI assays were also performed for C8 on A549 cell lines. Molecular dynamic analysis revealed that the stability of the C8–PLK1 protein complex during the 100 ns trajectory run was better than that of the C18–PLK1 protein complex. In addition, C8 showed lower IC50 values against the tested cell lines, in comparison to C18. Thus, C8 was selected for cell cycle, apoptosis, and DAPI analysis. Interestingly, C8 resulted in the significant cell cycle arrest of A549 cells at the G2/M phase, and annexin V-FITC/PI showed a significant increase (from 6.27% to 60.52%) in the percentage of apoptotic A549 cells. The present findings suggest that the anti-tubercular compound (C8) could be translated into a potent repurposed candidate against lung cancer. Nevertheless, in vivo assessment is necessary to further confirm the outcome and its clinical translation.

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Section: Cell Cycle Analysissupporting

confidence: 89%

Anticancer Activity of Anti-Tubercular Compound(s) Designed on Pyrrolyl Benzohydrazine Scaffolds: A Repurposing Study

et al. 2023

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“…Western blot analysis showed that p21 and p27 expression was significantly increased after o-GQD administration, which was consistent with the results from the apoptosis protein array. p21 and p27 affect the cell cycle by regulating the expression of CDKs and cyclin [ 19 ], and previous studies also indicated that the increase of p21 and p21 protein expression promotes G2/M cell cycle arrest [ 21 , 22 ]. Our results also revealed that o-GQD treatment down-regulated cyclin D1 and cyclin B1 expression.…”

Section: Discussionmentioning

confidence: 99%

Specific Forms of Graphene Quantum Dots Induce Apoptosis and Cell Cycle Arrest in Breast Cancer Cells

Shen

Hsieh

et al. 2023

IJMS

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Graphene quantum dots (GQDs), nanomaterials derived from graphene and carbon dots, are highly stable, soluble, and have exceptional optical properties. Further, they have low toxicity and are excellent vehicles for carrying drugs or fluorescein dyes. Specific forms of GQDs can induce apoptosis and could be used to treat cancers. In this study, three forms of GQDs (GQD (nitrogen:carbon = 1:3), ortho-GQD, and meta-GQD) were screened and tested for their potential to inhibit breast cancer cell (MCF-7, BT-474, MDA-MB-231, and T-47D) growth. All three GQDs decreased cell viability after 72 h of treatment and specifically affected breast cancer cell proliferation. An assay for the expression of apoptotic proteins revealed that p21 and p27 were up-regulated (1.41-fold and 4.75-fold) after treatment. In particular, ortho-GQD-treated cells showed G2/M phase arrest. The GQDs specifically induced apoptosis in estrogen receptor-positive breast cancer cell lines. These results indicate that these GQDs induce apoptosis and G2/M cell cycle arrest in specific breast cancer subtypes and could potentially be used for treating breast cancers.

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“…However, it appears that there are some differences in response to this compound between vascular SMCs and cancer cells. In cancer cells, CFI-400945 treatment upregulated the expression of p53, an essential regulator of the G2/M checkpoint [ 32 , 33 ], which activates cell cycle inhibitors, including p21 and p27 [ 34 ], and arrests the cell cycle. Our study revealed that CFI-400945 increased p27 protein levels but decreased p21 expression, suggesting that CFI-400945 treatment caused SMC cell cycle arrest mainly through the p53/p27 pathway.…”

Section: Discussionmentioning

confidence: 99%

Polo-like kinase 4 inhibitor CFI-400945 inhibits carotid arterial neointima formation but increases atherosclerosis

et al. 2023

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Neointima lesion and atherosclerosis are proliferative vascular diseases associated with deregulated proliferation of vascular smooth muscle cells (SMCs). CFI-400945 is a novel, highly effective anticancer drug that inhibits polo-like kinase 4 (PLK4) and targets mitosis. In this study, we aim to investigate how CFI-400945 affects the development of proliferative vascular diseases. In C57BL/6 mice, neointima formation was generated by complete carotid ligation. In apolipoprotein E knockout (ApoE−/−) mice fed a high-fat diet, atherosclerosis was induced by partial carotid ligation. CFI-400945 was directly applied to carotid arteries via a perivascular collar. Our results showed that CFI-400945 drastically inhibited neointima formation but significantly accelerated atherosclerosis. In vitro studies showed that CFI-400945 treatment induced SMC polyploidization and arrested cells in the G2/M phase. CFI-400945 treatment upregulated p53 and p27 expression but decreased p21 and cyclin B1 expression. CFI-400945 also induced SMC apoptosis, which was inhibited by hydroxyurea, a DNA synthesis inhibitor that inhibits polyploidization. Furthermore, CFI-400945 caused supernumerary centrosomes, leading to mitotic failure, resulting in polyploidization. In conclusion, CFI-400945 prevents carotid arterial neointima formation in C57BL/6 mice but accelerates atherosclerosis in ApoE−/− mice, likely through mitotic arrest and subsequent induction of polyploidization and apoptosis.

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JS‑K induces G2/M phase cell cycle arrest and apoptosis in A549 and H460 cells via the p53/p21WAF1/CIP1 and p27KIP1 pathways

Cited by 7 publications

References 45 publications

Anticancer Activity of Anti-Tubercular Compound(s) Designed on Pyrrolyl Benzohydrazine Scaffolds: A Repurposing Study

Anticancer Activity of Anti-Tubercular Compound(s) Designed on Pyrrolyl Benzohydrazine Scaffolds: A Repurposing Study

Specific Forms of Graphene Quantum Dots Induce Apoptosis and Cell Cycle Arrest in Breast Cancer Cells

Polo-like kinase 4 inhibitor CFI-400945 inhibits carotid arterial neointima formation but increases atherosclerosis

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