Abstract
Background: The purpose of this study was to investigate whether proteasome inhibition acts as a thermal sensitizing agent to induce tumor cell death in a colon cancer cell line. Methods: HT-29 colon cancer cells were exposed to hyperthermia (43°C) in the presence of proteasome inhibition for 1 h. Viable cell mass and apoptosis were measured by MTT and annexin V staining, respectively. Protein levels were determined by Western blot analysis. Results: A significant synergistic effect on cell viability with proteasome inhibition was noted under hyperthermic conditions compared to hyperthermia alone (p < 0.05). Increases in phosphorylated ERK and decreases in HSP27 levels were observed in the cells exposed to proteasome inhibition at 43°C. Pretreatment with an inhibitor of ERK yielded an additional increase in apoptosis when used in combination with proteasome inhibition and hyperthermia. Decreased expression of HSP27 by siRNA also resulted in increased thermally induced apoptotic cell death. Conclusions: Thermal sensitization through proteasome inhibition may represent a novel approach to increase the efficacy of hyperthermia as an anticancer modality.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 98-103 |
| Number of pages | 6 |
| Journal | Oncology |
| Volume | 73 |
| Issue number | 1-2 |
| DOIs | |
| State | Published - Mar 1 2008 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
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Proteasome inhibition potentiates the cytotoxic effects of hyperthermia in HT-29 colon cancer cells through inhibition of heat shock protein 27. / Chen, Fei; Rezavi, Reza; Wang, Cha Chi; Harrison, Lawrence E.
In: Oncology, Vol. 73, No. 1-2, 01.03.2008, p. 98-103.Research output: Contribution to journal › Article
TY - JOUR
T1 - Proteasome inhibition potentiates the cytotoxic effects of hyperthermia in HT-29 colon cancer cells through inhibition of heat shock protein 27
AU - Chen, Fei
AU - Rezavi, Reza
AU - Wang, Cha Chi
AU - Harrison, Lawrence E.
PY - 2008/3/1
Y1 - 2008/3/1
N2 - Background: The purpose of this study was to investigate whether proteasome inhibition acts as a thermal sensitizing agent to induce tumor cell death in a colon cancer cell line. Methods: HT-29 colon cancer cells were exposed to hyperthermia (43°C) in the presence of proteasome inhibition for 1 h. Viable cell mass and apoptosis were measured by MTT and annexin V staining, respectively. Protein levels were determined by Western blot analysis. Results: A significant synergistic effect on cell viability with proteasome inhibition was noted under hyperthermic conditions compared to hyperthermia alone (p < 0.05). Increases in phosphorylated ERK and decreases in HSP27 levels were observed in the cells exposed to proteasome inhibition at 43°C. Pretreatment with an inhibitor of ERK yielded an additional increase in apoptosis when used in combination with proteasome inhibition and hyperthermia. Decreased expression of HSP27 by siRNA also resulted in increased thermally induced apoptotic cell death. Conclusions: Thermal sensitization through proteasome inhibition may represent a novel approach to increase the efficacy of hyperthermia as an anticancer modality.
AB - Background: The purpose of this study was to investigate whether proteasome inhibition acts as a thermal sensitizing agent to induce tumor cell death in a colon cancer cell line. Methods: HT-29 colon cancer cells were exposed to hyperthermia (43°C) in the presence of proteasome inhibition for 1 h. Viable cell mass and apoptosis were measured by MTT and annexin V staining, respectively. Protein levels were determined by Western blot analysis. Results: A significant synergistic effect on cell viability with proteasome inhibition was noted under hyperthermic conditions compared to hyperthermia alone (p < 0.05). Increases in phosphorylated ERK and decreases in HSP27 levels were observed in the cells exposed to proteasome inhibition at 43°C. Pretreatment with an inhibitor of ERK yielded an additional increase in apoptosis when used in combination with proteasome inhibition and hyperthermia. Decreased expression of HSP27 by siRNA also resulted in increased thermally induced apoptotic cell death. Conclusions: Thermal sensitization through proteasome inhibition may represent a novel approach to increase the efficacy of hyperthermia as an anticancer modality.
UR - http://www.scopus.com/inward/record.url?scp=41549146961&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=41549146961&partnerID=8YFLogxK
U2 - 10.1159/000120997
DO - 10.1159/000120997
M3 - Article
C2 - 18337621
AN - SCOPUS:41549146961
VL - 73
SP - 98
EP - 103
JO - Oncology
JF - Oncology
SN - 0030-2414
IS - 1-2
ER -