Anti-Colon Cancer Effects of 6-Shogaol Through G2/M Cell Cycle Arrest by p53/p21-cdc2/cdc25A Crosstalk

2015 ◽  
Vol 43 (04) ◽  
pp. 743-756 ◽  
Author(s):  
Lian-Wen Qi ◽  
Zhiyu Zhang ◽  
Chun-Feng Zhang ◽  
Samantha Anderson ◽  
Qun Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Cycle Arrest ◽  
Strong Support ◽  
Cancer Chemoprevention ◽  
M Cell ◽  
Cycle Arrest ◽  
Hct 116 ◽  
Hct 116 Cells

Chemopreventive agents can be identified from botanicals. Recently, there has been strong support for the potential of 6-shogaol, a natural compound from dietary ginger (Zingiber officinale), in cancer chemoprevention. However, whether 6-shogaol inhibits the growth of colorectal tumors in vivo remains unknown, and the underlying anticancer mechanisms have not been well characterized. In this work, we observed that 6-shogaol (15 mg/kg) significantly inhibited colorectal tumor growth in a xenograft mouse model. We show that 6-shogaol inhibited HCT-116 and SW-480 cell proliferation with IC50 of 7.5 and 10 μM, respectively. Growth of HCT-116 cells was arrested at the G2/M phase of the cell cycle, primarily mediated by the up-regulation of p53, the CDK inhibitor p21waf1/cip1 and GADD45α, and by the down-regulation of cdc2 and cdc25A. Using p53-/- and p53+/+ HCT-116 cells, we confirmed that p53/p21 was the main pathway that contributed to the G2/M cell cycle arrest by 6-shogaol. 6-Shogaol induced apoptosis, mainly through the mitochondrial pathway, and the bcl-2 family might act as a key regulator. Our results demonstrated that 6-shogaol induces cancer cell death by inducing G2/M cell cycle arrest and apoptosis. 6-Shogaol could be an active natural product in colon cancer chemoprevention.

scholarly journals Ellagic acid induces cell cycle arrest and apoptosis via the TGF‑β1/Smad3 signaling pathway in human colon cancer HCT‑116 cells

2020 ◽  
Vol 44 (2) ◽  
pp. 768-776 ◽  
Author(s):  
Jinlu Zhao ◽  
Guodong Li ◽  
Jiufeng Wei ◽  
Shuwei Dang ◽  
Xiaotong Yu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Cycle Arrest ◽  
Ellagic Acid ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Cycle Arrest ◽  
Hct 116 ◽  
Hct 116 Cells ◽  
Tgf Β1

scholarly journals Saponins from edible spears of wild asparagus inhibit AKT, p70S6K, and ERK signalling, and induce apoptosis through G0/G1 cell cycle arrest in human colon cancer HCT-116 cells

2016 ◽  
Vol 26 ◽  
pp. 1-10 ◽  
Author(s):  
Sara Jaramillo ◽  
Francisco J.G. Muriana ◽  
Rafael Guillen ◽  
Ana Jimenez-Araujo ◽  
Rocio Rodriguez-Arcos ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Cycle Arrest ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Cycle Arrest ◽  
Hct 116 ◽  
G1 Cell Cycle Arrest ◽  
Hct 116 Cells

scholarly journals In Vitro Evaluation of Chemically Analyzed Hypericum Triquetrifolium Extract Efficacy in Apoptosis Induction and Cell Cycle Arrest of the HCT-116 Colon Cancer Cell Line

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4139 ◽  
Author(s):  
Shahinaz Mahajna ◽  
Sleman Kadan ◽  
Zipora Tietel ◽  
Bashar Saad ◽  
Said Khasib ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cell Line ◽  
Human Colon ◽  
Colon Cancer Cell Line ◽  
Cycle Arrest ◽  
Hct 116 ◽  
Hct 116 Cells

Naturally derived drugs and plant-based products are attractive commodities that are being explored for cancer treatment. This in vitro study aimed to investigate the role of Hypericum triquetrifolium (50% ethanol: 50% water) extract (HTE) treatment on apoptosis, cell cycle modulation, and cell cycle arrest in human colon cancer cell line (HCT-116). HTE induced cell death via an apoptotic process, as assayed by an Annexin V-Cy3 assay. Exposing HCT-116 cells to 0.064, 0.125, 0.25, and 0.5 mg/mL of HTE for 24 h led to 50 ± 9%, 71.6 ± 8%, 85 ± 5%, and 96 ± 1.5% apoptotic cells, respectively. HCT-116 cells treated with 0.25 and 0.5 mg/mL HTE for 3 h resulted in 38.9 ± 1.5% and 57.2 ± 3% cleavage of caspase-3-specific substrate, respectively. RT-PCR analysis revealed that the HTE extract had no effect on mRNA levels of Apaf-1 and NOXA. Moreover, the addition of 0.125 mg/mL and 0.25 mg/mL HTE for 24 h was clearly shown to attenuate the cell cycle progression machinery in HCT-116 cells. GC/MS analysis of the extract identified 21 phytochemicals that are known as apoptosis inducers and cell cycle arrest agents. All the compounds detected are novel in H. triquetrifolium. These results suggest that HTE-induced apoptosis of human colon cells is mediated primarily through the caspase-dependent pathway. Thus, HTE appears to be a potent therapeutic agent for colon cancer treatment.

scholarly journals Dual effect of 2-methoxyestradiol on cell cycle events in human osteosarcoma 143B cells.

2002 ◽  
Vol 49 (1) ◽  
pp. 59-65 ◽  
Author(s):  
Justyna Gołebiewska ◽  
Piotr Rozwadowski ◽  
Jan Henryk Spodnik ◽  
Narcyz Knap ◽  
Takashi Wakabayashi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Growth Inhibitor ◽  
Cytotoxic Action ◽  
M Cell ◽  
Human Osteosarcoma ◽  
Cycle Arrest ◽  
M Phase ◽  
The Stability

We have demonstrated for the first time that the steroid metabolite, 2-methoxyestradiol (2-ME) is a powerful growth inhibitor of human osteosarcoma 143 B cell line by pleiotropic mechanisms involving cell cycle arrest at two different points and apoptosis. The ability of 2-ME to inhibit cell cycle at the respective points has been found concentration dependent. 1 microM 2-ME inhibited cell cycle at G1 phase while 10 microM 2-ME caused G2/M cell cycle arrest. As a natural estrogen metabolite 2-ME is expected to perturb the stability of microtubules (MT) in vivo analogously to Taxol--the MT binding anticancer agent. Contrary to 2-ME, Taxol induced accumulation of osteosarcoma cells in G2/M phase of cell cycle only. The presented data strongly suggest two different mechanisms of cytotoxic action of 2-ME at the level of a single cell.

scholarly journals Antagonism of PP2A is an independent and conserved function of HIV-1 Vif and causes cell cycle arrest

2019 ◽  
Author(s):  
Sara Marelli ◽  
James C Williamson ◽  
Anna V Protasio ◽  
Adi Naamati ◽  
Edward JD Greenwood ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Cycle Progression ◽  
M Cell ◽  
Regulatory Subunits ◽  
Cycle Arrest ◽  
Identify Amino Acid ◽  
Necessary And Sufficient ◽  
Hiv 1

AbstractThe seminal description of cellular restriction factor APOBEC3G and its antagonism by HIV-1 Vif has underpinned two decades of research on the host-virus interaction. As well as APOBEC3G and its homologues, however, we have recently discovered that Vif is also able to degrade the PPP2R5 family of regulatory subunits of key cellular phosphatase PP2A (PPP2R5A-E) (Greenwood et al., 2016; Naamati et al., 2019). We now identify amino acid polymorphisms at positions 31 and 128 of HIV-1 Vif which selectively regulate the degradation of PPP2R5 family proteins. These residues covary across HIV-1 viruses in vivo, favouring depletion of PPP2R5A-E. Through analysis of point mutants and naturally occurring Vif variants, we further show that degradation of PPP2R5 family subunits is both necessary and sufficient for Vif-dependent G2/M cell cycle arrest. Antagonism of PP2A by HIV-1 Vif is therefore independent of APOBEC3 family proteins, and regulates cell cycle progression in HIV-infected cells.

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