The role of p21WAF1/Cip1 protein and chaperone inhbition in tumor cell response to therapy

Jagušt, Petra (2014) The role of p21WAF1/Cip1 protein and chaperone inhbition in tumor cell response to therapy. Diploma thesis, Faculty of Science > Department of Biology.

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Protein p21WAF1/Cip1 belongs to the Cip/ Kip family of cyclin dependent kinases inhibitors that mediates cell cycle arrest, activates senescence, has dual role in apoptosis modulation, and still unknown role in autophagy and in the interplay of these cell responses to therapy. Autophagy is a process of lysosomal degradation which maintains cell homeostasis, but it is also a stress-response mechanism. The aim of this work was to investigate the role of p21 in the activation of apoptosis, autophagy and cellular senescence through regulation of reactive oxygen species (ROS). For this purpose, we treated HCT 116 colon cancer cells with chemotherapeutic agents, cisplatin and doxorubicin after transduction with adenoviral vectors bearing p21 sequence or silencing p21 expression with small interfering RNAs. The results showed that the p21 activated senescence and autophagy by mechanism involving ROS accumulation, while it inhibited apoptosis. The results indicate the importance of ROS in the initiation of certain types of cell death. To test the influence of HSP90 and HSP70 inhibitors on cell viability after treatment with chemotherapeutic agents, we used geldanamicin or pifitrin-μ. We showed that the inhibition of HSP90 with geldanamicin slightly enhanced the effect of doxorubicin, while pifitrin-μ had no effect on the cell viability.

Item Type: Thesis (Diploma thesis)
Keywords: protein p21, reactive oxygen species, cellular senescence, apoptosis, autophagy, molecular chaperones
Supervisor: Kralj, Marijeta
Co-supervisor: Matulić, Maja
Date: 2014
Number of Pages: 82
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Grozdana Sirotic
Date Deposited: 25 Mar 2014 14:08
Last Modified: 23 Sep 2014 08:54

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