Hypoxia-inducible factor 1-alpha up-regulates the expression of phospholipase D2 in colon cancer cells under hypoxic conditions

2014 ◽  
Vol 32 (1) ◽  
Author(s):  
Maoxi Liu ◽  
Kunli Du ◽  
Zhongxue Fu ◽  
Shouru Zhang ◽  
Xingye Wu
Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 113 ◽  
Author(s):  
Alaa A. A. Aljabali ◽  
Hamid A. Bakshi ◽  
Faruck L. Hakkim ◽  
Yusuf A. Haggag ◽  
Khalid M. Al-Batanyeh ◽  
...  

Piceatannol (PIC) is known to have anticancer activity, which has been attributed to its ability to block the proliferation of cancer cells via suppression of the NF-kB signaling pathway. However, its effect on hypoxia-inducible factor (HIF) is not well known in cancer. In this study, PIC was loaded into bovine serum albumin (BSA) by desolvation method as PIC–BSA nanoparticles (NPs). These PIC–BSA nanoparticles were assessed for in vitro cytotoxicity, migration, invasion, and colony formation studies and levels of p65 and HIF-1α. Our results indicate that PIC–BSA NPs were more effective in downregulating the expression of nuclear p65 and HIF-1α in colon cancer cells as compared to free PIC. We also observed a significant reduction in inflammation induced by chemical colitis in mice by PIC–BSA NPs. Furthermore, a significant reduction in tumor size and number of colon tumors was also observed in the murine model of colitis-associated colorectal cancer, when treated with PIC–BSA NPs as compared to free PIC. The overall results indicate that PIC, when formulated as PIC–BSA NPs, enhances its therapeutic potential. Our work could prompt further research in using natural anticancer agents as nanoparticels with possible human clinical trails. This could lead to the development of a new line of safe and effective therapeutics for cancer patients.


2017 ◽  
Vol 118 (7) ◽  
pp. 1868-1878 ◽  
Author(s):  
Martha L. Pinzón-Daza ◽  
Yenith Cuellar-Saenz ◽  
Francisco Nualart ◽  
Alejandro Ondo-Mendez ◽  
Lilia Del Riesgo ◽  
...  

2018 ◽  
Vol 66 (4) ◽  
pp. 543-550 ◽  
Author(s):  
Martha Leonor Pinzón-Daza ◽  
Yenith Cuellar ◽  
Alejandro Ondo ◽  
Luisa Matheus ◽  
Lilia Del Riesgo ◽  
...  

Introduction: Drug resistance mechanisms may be associated with decreased cell death and its induction may depend on the response to oxidative stress caused by hypoxia. The correlation between hypoxia-inducible factor HIF-1α, the number of reactive oxygen species and their effect on cell survival has not yet been evaluated.Objective: The purpose of this study was to evaluate the effect of HIF-1α activity and reactive oxygen species (ROS) accumulation in apoptosis of colon cancer cells.Materials and methods: HT29 colon cancer cells were treated with CoCl2 or doxorubicin and the activity of HIF-1α was determined by ELISA assay. ROS were determined using fluorescence probe carboxy-H2DFFDA. Apoptosis was assessed by caspase-3 activation analysis, and PUMA and BAX mRNA levels by qRT-PCR. The reduction of the antiapoptotic effect due to hypoxia was attenuated by use of the endonuclease APE-1 (E3330) inhibitor. The endonuclease E3330 APE-1 inhibitor allowed evaluating the effect of ROS generated by doxorubicin and CoCl2 on apoptosis.Results: Chemical hypoxia in combination with doxorubicin is an oxidative stressor in HT29 cells and induces a reduction in the apoptotic process in a time-dependent manner.Conclusion: Resistance to hypoxia and doxorubicin-mediated cell death could be controlled by a mechanism related to the activity of HIF-1α and the amount of reactive oxygen species generated.


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