Mechanisms of arsenic trioxide induced apoptosis of human cervical cancer HeLa cells and protection by Bcl-2

1999 ◽  
Vol 42 (6) ◽  
pp. 635-643 ◽  
Author(s):  
Youping Deng ◽  
Chen Lin ◽  
Jie Zheng ◽  
Xiao Liang ◽  
Jieping Chen ◽  
...  
2019 ◽  
Vol 2019 ◽  
pp. 1-26
Author(s):  
Liubing Hu ◽  
Yan Wang ◽  
Zui Chen ◽  
Liangshun Fu ◽  
Sheng Wang ◽  
...  

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent cancer cell apoptosis-inducing factor that can induce apoptosis in a variety of cancer cells. However, resistance to TRAIL in cancer cells is a huge obstacle in creating effective TRAIL-targeted clinical therapies. Thus, agents that can either enhance the effect of TRAIL or overcome its resistance are needed. In this study, we combined TRAIL with SNX-2112, an Hsp90 inhibitor we previously developed, to explore the effect and mechanism that SNX-2112 enhanced TRAIL-induced apoptosis in cervical cancer cells. Our results showed that SNX-2112 markedly enhanced TRAIL-induced cytotoxicity in HeLa cells, and this combination was found to be synergistic. Additionally, we found that SNX-2112 sensitized TRAIL-mediated apoptosis caspase-dependently in TRAIL-resistant HeLa cells. Mechanismly, SNX-2112 downregulated antiapoptosis proteins, including Bcl-2, Bcl-XL, and FLIP, promoted the accumulation of reactive oxygen species (ROS), and increased the expression levels of p-JNK and p53. ROS scavenger NAC rescued SNX-2112/TRAIL-induced apoptosis and suppressed SNX-2112-induced p-JNK and p53. Moreover, SNX-2112 induced the upregulation of death-receptor DR5 in HeLa cells. The silencing of DR5 by siRNA significantly decreased cell apoptosis by the combined effect of SNX-2112 and TRAIL. In addition, SNX-2112 inhibited the Akt/mTOR signaling pathway and induced autophagy in HeLa cells. The blockage of autophagy by bafilomycin A1 or Atg7 siRNA abolished SNX-2112-induced upregulation of DR5. Meanwhile, ROS scavenger NAC, JNK inhibitor SP600125, and p53 inhibitor PFTα were used to verify that autophagy-mediated upregulation of DR5 was regulated by the SNX-2112-stimulated activation of the ROS-JNK-p53 signaling pathway. Thus, the combination of SNX-2112 and TRAIL may provide a novel strategy for the treatment of human cervical cancer by overcoming cellular mechanisms of apoptosis resistance.


PLoS ONE ◽  
2014 ◽  
Vol 9 (8) ◽  
pp. e105768 ◽  
Author(s):  
Tao Xu ◽  
Qiuying Pang ◽  
Dong Zhou ◽  
Aiqin Zhang ◽  
Shaman Luo ◽  
...  

2016 ◽  
Vol 11 (4) ◽  
pp. 2411-2419 ◽  
Author(s):  
LUYAN SHEN ◽  
NAIYAN WEN ◽  
MEIHUI XIA ◽  
YU ZHANG ◽  
WEIMIN LIU ◽  
...  

2021 ◽  
Vol 12 (21) ◽  
pp. 6310-6319
Author(s):  
Jing Chen ◽  
Cunmin Zhou ◽  
Juan Yi ◽  
Jingjing Sun ◽  
Bei Xie ◽  
...  

2021 ◽  
Vol 7 (5) ◽  
pp. 3470-3478
Author(s):  
Li Zuo ◽  
Ting Li ◽  
Fuxiang Liu

Cervical cancer is a serious threat to women’s health. In recent years, the incidence rate has increased year by year, and the incidence of cervical cancer tends to be younger. Because of its characteristics of easy recurrence and easy metastasis, the drug therapy of cervical cancer has attracted increasing attention. Coixen ester has anti-cancer and immunomodulatory effects. After years of clinical research, it has been shown to be effective against a variety of cancers and has a growth inhibitory effect on tumor cells. This article aims to study the mechanism of Coixen ester-induced apoptosis of human cervical cancer HeLa cells. This article puts forward what are the causes of cervical cancer, and analyzes the positive effects of traditional Chinese medicine in the prevention and treatment of cervical cancer. During the experiment, the MTT method was used to study the effect of the complex on the proliferation of HeLa cells. The experimental results in this article show that a certain concentration of Coixen ester solution can inhibit cell proliferation and can also reduce cell viability to about 0.35.


2021 ◽  
pp. 1-27
Author(s):  
Nabil Mohie Abdel-Hamid ◽  
Moustafa Fathy ◽  
Chika Koike ◽  
Toshiko Yoshida ◽  
Motonori Okabe ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Yu Wu ◽  
Xianjing Hu ◽  
Liyan Song ◽  
Jianhua Zhu ◽  
Rongmin Yu

Inflammation is known to be closely associated with the development of cancer. The study was launched in human cervical cancer HeLa cells to investigate the antitumor and anti-inflammatory effects of P2, a marine polypeptide fraction from an important fishery resourceArca subcrenata. The basic research showed that P2 could suppress the production of nitric oxide in LPS-induced RAW264.7 macrophage cells as well as the secretion of inflammatory cytokines IL-6 and TNF-αin human cervical cancer HeLa cells. For the molecular mechanisms, P2 was shown to downregulate the gene expression of proinflammatory cytokines IL-6 and IL-8 and to inhibit the COX-2 and iNOS-related pathways in HeLa cells. In consequence, P2 might inhibit tumor development by blocking the interaction between tumor microenvironment and proinflammatory mediators. All findings indicate that P2 possesses the potential to be developed as a novel agent for cancer therapy.


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