scholarly journals Effects of 17-allylamino-17-demethoxygeldanamycin on the induction of apoptosis and cell cycle arrest in HCT-116 cells

2017 ◽  
Vol 14 (2) ◽  
pp. 2177-2185 ◽  
Author(s):  
Xuerong Zhao ◽  
Jianping Wang ◽  
Lijun Xiao ◽  
Qian Xu ◽  
Enhong Zhao ◽  
...  
2015 ◽  
Vol 43 (04) ◽  
pp. 743-756 ◽  
Author(s):  
Lian-Wen Qi ◽  
Zhiyu Zhang ◽  
Chun-Feng Zhang ◽  
Samantha Anderson ◽  
Qun Liu ◽  
...  

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.


2020 ◽  
Vol 44 (2) ◽  
pp. 768-776 ◽  
Author(s):  
Jinlu Zhao ◽  
Guodong Li ◽  
Jiufeng Wei ◽  
Shuwei Dang ◽  
Xiaotong Yu ◽  
...  

2016 ◽  
Vol 26 ◽  
pp. 1-10 ◽  
Author(s):  
Sara Jaramillo ◽  
Francisco J.G. Muriana ◽  
Rafael Guillen ◽  
Ana Jimenez-Araujo ◽  
Rocio Rodriguez-Arcos ◽  
...  

2011 ◽  
Vol 89 (3) ◽  
pp. 287-298 ◽  
Author(s):  
Wei Liu ◽  
Qinsheng Dai ◽  
Na Lu ◽  
Libin Wei ◽  
Jun Ha ◽  
...  

We recently established that LYG-202, a new flavonoid with a piperazine substitution, exerts an anti-tumor effect in vivo and in vitro. In the present study, we demonstrate that LYG-202 induces G1/S phase arrest and apoptosis in human colorectal carcinoma HCT-116 cells. Data showed that the blockade of the cell cycle was associated with increased p21WAF1/Cip1 and Rb levels and reduced expression of cyclin D1, cyclin E, and CDK4. Moreover, PARP cleavage, activation of caspase-3, caspase-8, and caspase-9, and an increased ratio of Bax/Bcl-2 were detected in LYG-202-induced apoptosis. Additionally, activation of p53 resulted in the up-regulation of its downstream targets PUMA and p21WAF1/Cip1, as well as the down-regulation of its negative regulator MDM2, suggesting that the p53 pathway may play a crucial role in LYG-202-induced cell cycle arrest and apoptosis. Furthermore, siRNA knockdown of p53 attenuated the G1 cell cycle arrest and apoptosis induced by LYG-202, as the effects of LYG-202 on up-regulation of p21WAF1/Cip1 and down-regulation of Bcl-2 and pro-caspase-3 were partly inhibited in p53 siRNA transfected cells compared with control siRNA transfected cells. Collectively, these data indicate that LYG-202 exerts its anti-tumor potency by activating the p53–p21 pathway for G1/S cell cycle arrest and apoptosis in colorectal cancer cells.


Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4139 ◽  
Author(s):  
Shahinaz Mahajna ◽  
Sleman Kadan ◽  
Zipora Tietel ◽  
Bashar Saad ◽  
Said Khasib ◽  
...  

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.


2015 ◽  
Vol 117 (5) ◽  
pp. 1262-1272 ◽  
Author(s):  
Nadia Mustapha ◽  
Aline Pinon ◽  
Youness Limami ◽  
Alain Simon ◽  
Kamel Ghedira ◽  
...  

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