Bufalin induces G0/G1 phase arrest through inhibiting the levels of cyclin D, cyclin E, CDK2 and CDK4, and triggers apoptosis via mitochondrial signaling pathway in T24 human bladder cancer cells

Huang, Wen Wen; Yang, Jai Sing; Pai, Shu Jen; Wu, Ping; Chang, Sun‐Yran; Chueh, Fu Shin; Fan, Ming; Chiou, Shang Ming; Kuo, Hsiu Maan; Yeh, Chun Chieh; Chen, Po‐Yuan; Tsuzuki, Minoru; Chung, Jing Gung

doi:10.1016/j.mrfmmm.2011.09.010

Cited by 58 publications

(49 citation statements)

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“…The cell cycle is regulated by the temporal activation of different cyclin-dependent kinase (CDK)/cyclin complexes in eukaryotic cells [36] . The cell cycle progression from G 1 phase to S phase is initiated by phosphorylated Rb, which is regulated by CDK/cyclin complexes and multiple suppressor proteins [37] . The cyclin E-CDK2 complex is required for the G 1 -S transition in the cell cycle, and the activity of this complex is thought to be required for the G 1 -S transition [35,38] .…”

Section: Discussionmentioning

confidence: 99%

In vitro anti-cancer activity of chamaejasmenin B and neochamaejasmin C isolated from the root of Stellera chamaejasme L

et al. 2012

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Aim: To examine the anti-cancer effects of chamaejasmenin B and neochamaejasmin C, two biflavonones isolated from the root of Stellera chamaejasme L (known as the traditional Chinese herb Rui Xiang Lang Du) in vitro. Methods: Human liver carcinoma cell lines (HepG2 and SMMC-7721), a human non-small cell lung cancer cell line (A549), human osteosarcoma cell lines (MG63, U2OS, and KHOS), a human colon cancer cell line (HCT-116) and a human cervical cancer cell line (HeLa) were used. The anti-proliferative effects of the compounds were measured using SRB cytotoxicity assay. DNA damage was detected by immunofluorescence and Western blotting. Apoptosis and cell cycle distribution were assessed using flow cytometry analysis. The expression of the related proteins was examined with Western blotting analysis. Results: Both chamaejasmenin B and neochamaejasmin C exerted potent anti-proliferative effects in the 8 human solid tumor cell lines. Chamaejasmenin B (the IC 50 values ranged from 1.08 to 10.8 μmol/L) was slightly more potent than neochamaejasmin C (the IC 50 values ranged from 3.07 to 15.97 μmol/L). In the most sensitive A549 and KHOS cells, the mechanisms underlying the anti-proliferative effects were characterized. The two compounds induced prominent expression of the DNA damage marker γ-H2AX as well as apoptosis. Furthermore, treatment of the cells with the two compounds caused prominent G 0 /G 1 phase arrest. Conclusion: Chamaejasmenin B and neochamaejasmin C are potential anti-proliferative agents in 8 human solid tumor cell lines in vitro via inducing cell cycle arrest, apoptosis and DNA damage.

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Section: Discussionmentioning

confidence: 99%

In vitro anti-cancer activity of chamaejasmenin B and neochamaejasmin C isolated from the root of Stellera chamaejasme L

et al. 2012

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“…Cells (2x10 5 cells/well) were maintained in 24-well plates and then were treated with 0, 50, 100 and 200 nM of bufalin. Cell morphological examination was determined utilizing a phase-contrast microscope as previously described (19). Chromatin condensation was detected using the DAPI staining method as previously described (19,28).…”

Section: Methodsmentioning

confidence: 99%

“…It has been reported that the topoisomerase inhibitor, etoposide and adriamycin are widely prescribed anticancer drugs which inhibit cell proliferation and induce apoptosis in numerous cancer cell lines (17,18). Our earlier study showed that bufalin is found to inhibit cell growth at G 0 /G 1 phase of the cell cycle and to induce apoptosis in a dose-dependent manner, which was associated with both mitochondria-regulated and death receptor-initiated pathways (19). Furthermore, bufalin has been found to inhibit Bcl-2 and c-myc in human leukemia cells (20) and to induce apoptosis of human prostate cancer cells in part with Fas stimulation, cyto-cytochrome c release and caspase activation (15).…”

Section: Introductionmentioning

confidence: 98%

AKT serine/threonine protein kinase modulates bufalin-triggered intrinsic pathway of apoptosis in CAL 27 human oral cancer cells

Tsai

Lee

et al. 2012

International Journal of Oncology

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Abstract. Bufalin has been reported to induce apoptosis in a variety of cancers but little is demonstrated in oral squamous cell carcinoma (OSCC) cells. The present study investigated the inhibition of proliferation, cell cycle arrest and apoptotic effects of bufalin in CAL 27 human oral cancer cells. Bufalin inhibited the growth of CAL 27 cells in a concentration-dependent manner and an IC 50 value of bufalin was about 125 nM for 24 h treatment using the MTT assay. Moreover, the cell cycle distribution was arrested at the G 0 /G 1 phase in CAL 27 cells after bufalin exposure. Upon bufalin stimulation, the expression of Bcl-2 was significantly decreased while that of cytochrome c, Apaf-1 and AIF was increased compared to the control group by western blot analysis. An increase in the expression of the active form of caspases was found in bufalin-treated cells, and the caspase activities were also elevated. Bufalin-triggered apoptosis was blocked by specific inhibitors of caspase-9 (z-LEHD-fmk) and caspase-3 (z-DEVD-fmk), respectively. In contrast, CAL 27 cells overexpressing constitutively active AKT (CAL 27/CA-AKT) were exposed to bufalin at different concentrations, and cell growth remained unchanged. Bufalin exhibited minimal apoptotic effects on CAL 27/CA-AKT cells. Taken together, bufalin induced G 0 /G 1 phase arrest and provoked the intrinsic apoptotic pathway via AKT activation in CAL 27 cells. Our data suggest that bufalin could be potentially efficacious in the treatment of oral cancer in the future.

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“…CDK2 belongs to the CDK family of serine/threonine protein kinases, and is involved in the regulation of this cell cycle stage (Dulić et al, 1992). The activation of CDK2 through its interaction with cyclin E constitutes an indispensable event in the G1/S transition (Huang et al, 2012). The cyclin E/CDK2 complex promotes G1 progression by phosphorylating retinoblastoma protein (Rb; Hinds et al, 1992), causing the release of the transcription factor E2F from the Rb/E2F complex, which in turn promotes the expression of genes that drive the G1/S phase transition (Zhang et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Molecular cloning and functional characterization of cyclin E and CDK2 from Penaeus monodon

Zhao

Qiu

2016

Genet. Mol. Res.

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ABSTRACT. Reduced reproductive performance of the black tiger shrimp (Penaeus monodon) has caused economic losses and hampered the fishing industry. Detailed investigation of the molecular mechanism by which the cell cycle is regulated in this organism is needed to understand the development and maturation of ovaries and oocytes, with a view to improving reproductive capacity. Cell cycle progression is mainly determined by cyclin-dependent kinase (CDK) and cyclin complexes, the cyclin E/CDK2 complex playing a key role in G1/S transition. However, knowledge of the interplay between cyclin E and CDK2 in invertebrates remains limited. In this study, full-length P. monodon cyclin E (Pmcyclin E) and CDK2 (PmCDK2) sequences were cloned. The open reading frame of Pmcyclin E was 1263 bp in 2 C. Zhao et al. Genetics and Molecular Research 15 (3): gmr.15038716 length and encoded a 47.9-kDa protein, while that of PmCDK2 was 921 bp, encoding a protein of 34.9 kDa. Recombinant cyclin E and CDK2 proteins were expressed in Escherichia coli and purified by Ni-chelating affinity chromatography. In addition, a pull-down assay was performed to identify any interaction between Pmcyclin E and PmCDK2. This research provides a basis for the study of the functional mechanisms of the cyclin E/CDK2 complex in shrimp, further enriching our knowledge of invertebrate cell cycle regulation.

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Bufalin induces G0/G1 phase arrest through inhibiting the levels of cyclin D, cyclin E, CDK2 and CDK4, and triggers apoptosis via mitochondrial signaling pathway in T24 human bladder cancer cells

Cited by 58 publications

References 31 publications

In vitro anti-cancer activity of chamaejasmenin B and neochamaejasmin C isolated from the root of Stellera chamaejasme L

In vitro anti-cancer activity of chamaejasmenin B and neochamaejasmin C isolated from the root of Stellera chamaejasme L

AKT serine/threonine protein kinase modulates bufalin-triggered intrinsic pathway of apoptosis in CAL 27 human oral cancer cells

Molecular cloning and functional characterization of cyclin E and CDK2 from Penaeus monodon

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