- Email: [email protected]
W1739 ROS-Dependent Degradation of HSP90 in Deoxycholate-Induced Apoptosis in Gastric Cancer Epithelial Cells
W1737
no pretreatment or were preincubated with antioxidants [vitamin C (VitC), N-acetyl cysteine (NAC) and quercetin (Q)], or proteasome inhibitors [proteasome inhibitor I (PI), lactacystin (LC) and MG-132)] for 16 hours prior to addition of DC. ROS-mediated protein modification was measured by immunodetection of carbonyl groups using the OxyELISA oxidized protein kit (Millipore). Caspase-3 activation, poly(ADP-ribose)polymerase (PARP) cleavage, and HSP90 fragmentation were detected in whole lysates by Western blot analysis. Results: DC (300 μM) induced the oxidative modification of proteins and increased carbonyl levels to 1.15 ± 0.02 and 2.05± 0.15 nmoles carbonyls/mg protein after 2 and 4 hours of treatment as compared to 0.25 ± 0.01 nmoles carbonyls/mg protein in untreated cells (p< 0.001). Significant increase of oxidative status of proteins correlated with HSP90 cleavage to the 45 KDa fragment, caspase-3 activation and PARP cleavage. Antioxidants significantly inhibited the DC-induced carbonyl production (NAC 90.2 %, Q 46.3 %, VitC 43.9 %) as well as HSP90 degradation and caspase-3 activation. HSP90 processing was not dependent on proteasome activation since none of selected proteasome inhibitors protected HSP90 from cleavage. Conclusion: These results demonstrate that DC-induced degradation of HSP90 to a 45 KDa fragment is mediated through a mechanism involving ROS production, but is not dependent on proteasome activation. ROS-mediated inhibition of HSP90 chaperoning ability is essential for activation of pro-apoptotic signaling in AGS cells exposed to DC.
AGA Abstracts
Advanced Colorectal Neoplasia is Associated With Telomere Shortening Within the Normal Colorectal Mucosa Daniel L. Worthley, Nathan O'Callaghan, Shuji Ogino, Natsumi Irahara, Vicki L. Whitehall, Barbara A. Leggett, Michael Fenech Introduction: In carcinogenesis, telomere shortening can promote chromosomal instability (CIN). Advanced adenomas are the pathological precursors to CIN-pathway colorectal cancers (CRC). Telomere shortening is evident within advanced colorectal adenomas. This study investigated whether telomere attrition was present in the normal colorectal mucosa in patients diagnosed with advanced colorectal neoplasia. Methods: Seventy-one patients were prospectively studied. Colonoscopic biopsies were taken from normal mucosa within the cecum, transverse colon, sigmoid colon and rectum. Telomere length was determined in each biopsy using a quantitative real-time PCR technique. Telomere lengths (kb/diploid genome) were reported for each site as well as for the proximal (mean of cecum and transverse), distal (mean of sigmoid and rectum) and entire colorectum (pancolorectal, mean of all 4 sites). These results were log transformed and examined for univariate and multivariate associations with colorectal region, patient age, smoking and the presence of advanced neoplasia (>10mm, high-grade dysplasia or villous change). Results: 34 patients had normal colonoscopies, 13 had simple adenomas, 9 had advanced neoplasia (8 advanced adenomas and 1 cancer) and 15 had non-adenomatous polyps. Mean age was 59 years (range 28 - 80 years). The mean pancolorectal telomere length was 768 kb/diploid genome. Patients with advanced colorectal neoplasia had significantly shorter telomeres in their background normal mucosa than those without advanced neoplasia, 672 vs. 781 kb/diploid genome, p=0.024. On simple logistic regression pancolorectal telomere length was significantly and inversely associated with the presence of advanced neoplasia, OR=0.010, p=0.031. There was no significant relationship between colorectal region and telomere length, distal vs. proximal mucosal telomere length was 748 vs. 786 kb/diploid genome, p=0.14. In this study there was no clear relationship between age and telomere length. On multivariate logistic regression, using a model that included significant family history, prior adenomas and age, pancolorectal telomere length was independently and inversely associated with the presence of advanced adenomas (OR = 0.002, p = 0.027). Conclusions: Telomere length in the normal colorectal mucosa is an independent predictor of advanced colorectal neoplasia. Telomere attrition in the colorectal field may be an important indicator of, or even prelude to, advanced colorectal neoplasia.
W1740 Anti-Cancer Effects of Xanthorrhizol and Astaxanthine in Esophageal Cancer Cell Lines Moon Kyung Joo, Jong-Jae Park, Beom Jae Lee, Jong Yeol Kim, Jin Ki Hwang, Seung Goun Hong, Keyhyeon Kim, Ja In Park, Joo Yeon Oh, Ji Hoon Kim, Jong Eun Yeon, Jae Seon Kim, Kwan Soo Byun, Young-Tae Bak, Sun-Joong Kim, Seok-Keun Choi Background: Xanthorrhizol (XT) is a natural sesquiterpenoid compound isolated from the rhizome of Curcuma xanthorrhizza Roxb (Zingerberaceae). Recent In Vitro studies support the role of XT as an anti-cancer agent in hepatoma or breast cancer cell lines. Astaxanthin (AX) and α-tocopherol (AT) also have shown anti-cancer effects on various gastrointestinal cancer cell lines. We assessed the effect of XT as well as combination including AX and AT on human esophageal squamous cancer cell lines to show the mechanism of anti-cancer effect and its therapeutic potential. Materials and methods: Two human esophageal squamous cancer cell lines (TE-1, TE-4) were exposed to XT, AX and AT. Quantification of proliferation was performed by MTT assay. After deciding adequate concentration of these agents and treating them for 24 hours, western blot analysis was done do investigate the protein expression of p-p38, p-AKT, cyclin D1, p27 and caspase-3. Results: More than 50% inhibition of cell proliferation by XT by a dose-dependent manner was observed in both cell lines, and similar pattern by AX and AT in TE-4 cell line. Western blot analyses demonstrated that XT alone reduced the protein expression of p-AKT and cyclin D1 in both cell lines. Double combination of XT and AX, and triple combination of XT, AX and AT also reduced the expression of p-AKT and cyclin D1, and increased that of caspase-3 more prominently than XT as a single agent in both cell lines. Conclusion: XT is effective in inhibition of cell proliferation and thought to modulate oncogenic pathway by p-AKT and cyclin D1. Our results also suggest that combination of XT and other anti-cancer agents has cooperative inhibitory effect on the apoptosis of human esophageal squmous cancer cell lines.
W1738 Role of TLR4 in Carcinogenesis and Tumor Progression of Colorectal Cancer Noha E. El-Sakka, Georgina L. Hold, Emad El-Omar Background: There is now a clear association between chronic inflammation and carcinogenesis. Inflammation is accompanied by generation of free radicals, cytokines, and growth factors that favour carcinogenesis by stimulating angiogenesis, and inducing cell proliferation. Toll-like receptor 4 (TLR4) is the main receptor involved in recognition of bacterial endotoxin (LPS) and promotes immunoinflammatory responses by intestinal epithelial cells. TLR4 has a role in promoting tumor growth and carcinogenesis and is a potential therapeutic target in cancer therapy. Blockade of TLR4 signalling in other cancer models is associated with retarded tumour growth and prolonged survival. However little is currently known within the context of CRC. Aim: To examine the pathophysiologic role of TLR4 in CRC carcinogenesis. Methods: Pre-designed silencer siRNA for TLR4 was used to transfect the human CRC cell line SW480. Following siRNA, cells were stimulated with E. coli LPS (2 μg/ml) and various markers of carcinogenesis were compared between wildtype and TLR4 knockdown SW480 cells. For cell proliferation, colorimetric CellTiter 96 AQueous One assay was used to measure formazan product. Apoptosis assessment was performed by Annexin-V-FLUOS using FACSCalibur. A panel of 5 cytokines (IL-8, IL-6, IL-10, IL-1β and TNF-α) were also measured. Mann-Whitney U test was used and p-values < 0.05 were considered statistically significant. Results: Following LPS stimulation of SW480 cells we were able to demonstrate effective TLR4 knockdown following siRNA incorporation. There was a significant reduction in LPS-stimulated cell proliferation: TLR4 siRNA transfection 88.5 (range - 84.1 -91.5) compared to 95.6 (range - 88.9-121.2) for non-transfection, (p =0.003). Apoptosis assessment showed that cells with siRNA/silenced TLR4 had significantly higher percentages of apoptotic cells compared to no siRNA/high TLR4: 14.7% (range - 7.4-16.8%) vs 6.8% (range - 4.0412.8%)(p=0.0028). TLR4 siRNA transfected cells expressed lower IL-6 protein levels at 6 hours compared to normal cells: 1.38pg/ml (range 1.13-1.69) vs 1.75pg/ml (range 1.094.9) (p= 0.04)). Conclusions: Our results suggest that blockade of TLR4 leads to a reduction in tumour cell proliferation, an increase in tumour cell death and a reduction in proinflammatory cytokine production. It remains to be shown whether similar effects could be achieved In Vivo and further work is required to elucidate the molecular mechanisms involved. However, the prospect of achieving these effects offers an opportunity for therapeutic intervention in the context of CRC.
W1741 Effect of Trastuzumab on Phosphorylated Histone H2AX Induced by Topoisomerase-1 Inhibitor (SN-38) in Gastric Cancer Cell Lines With or Without HER2 Expression Mihoko Yamade, Takahisa Furuta, Mitsushige Sugimoto, Chise Kodaira, Masafumi Nishino, Takahiro Uotani, Mutsuhiro Ikuma Aim: Molecular targeting therapy is an important strategy in treating various cancers. Human epidermal growth factor receptor 2 (HER2), a member of the epidermal growth factor receptor family, is a target of such therapeutic strategies and is sometimes found expressed on gastric cancer cells. Recent In Vitro and In Vivo studies have demonstrated that trastuzumab enhances the therapeutic efficacy of antineoplastic agents in treating gastric cancer. Trastuzumab inhibits the signaling pathway from the HER2 receptor and induces antibody-dependent cell-mediated cytotoxicity (ADCC). However, the mechanism by which trastuzumab enhances the cellular toxicity of antineoplastic agents has not been fully elucidated. When a topoisomerase I inhibitor such as SN-38 induces a DNA double strand breaks (DSBs) in cells, histone H2AX is immediately phosphorylated to γH2AX, the sensitive marker of DSBs. Here, we investigated the effect of trastuzumab on SN-38-induced γH2AX in cells with or without HER2 expression. Methods: Gastric cancer cell lines used in the present study were NCI-N87, with strong expression of HER2, and MKN74, which lacks HER2 expression. Both cell lines were exposed to SN-38 with and without trastuzumab, and induction of γH2AX was determined by immunofluorescence and Western blot. The influence of trastuzumab on the cytotoxic effects of SN-38 was measured by MTT and cell count assays, and the effect of trastuzumab on cell cycle progression was determined by flow cytometry. Results: Trastuzumab administered alone induced γH2AX in NCI-N87 cells, but not in MKN74 cells. Further, when administered after SN-38, trastuzumab increased γH2AX induced by SN-38 and enhanced the cytotoxic effect of SN-38 in NCI-N87 cells, but not in MKN74 cells. However, when administered before SN-38, trastuzumab instead reduced γH2AX induction by SN-38 in a dose dependent manner in NCI-N87 cells, but exerted no effect in MKN74 cells. Trastuzumab administered at any check point induced S phase delay in NCI-N87 cells, but not in MKN74 cells. Conclusion: Results from the present study suggest that trastuzumab disrupts the repair of DSBs induced by SN-38 in an HER2-dependent manner. However, trastuzumab also hinders cell cycle progression, which thereby diminishes the replication-dependent generation of DSBs by SN-38. Therefore, whether or not trastuzumab enhances the cytotoxicity of SN-38 depends on the order of administration of SN-38 and trastuzumab.
W1739 ROS-Dependent Degradation of HSP90 in Deoxycholate-Induced Apoptosis in Gastric Cancer Epithelial Cells Maria J. Redlak, Thomas A. Miller Introduction: Heat shock protein 90 (HSP90) is essential for correct protein folding and assembly of some critical proteins which are important for cell survival. In many cancer cells HSP90 is over-expressed and participates in malignant transformation through stabilization of mutated genes and enhancement of cancer cell survival. We have previously shown that deoxycholate (DC) inhibits pro-survival PI3K/Akt/HSP90 signaling in gastric cancer mucosal cells by dephosphorylation of Akt and degradation of HSP90 to a 45 KDa fragment. It has been reported that the chaperoning function of HSP90 may be disrupted by cleavage induced by hydrogen peroxide or other reactive oxygen species (ROS). We examined the hypothesis that HSP90 degradation is mediated by ROS production in gastric cancer cells exposed to deoxycholate. Methods: AGS cells (human gastric adenocarcinoma mucosal cells) received
AGA Abstracts
S-730
no pretreatment or were preincubated with antioxidants [vitamin C (VitC), N-acetyl cysteine (NAC) and quercetin (Q)], or proteasome inhibitors [proteasome inhibitor I (PI), lactacystin (LC) and MG-132)] for 16 hours prior to addition of DC. ROS-mediated protein modification was measured by immunodetection of carbonyl groups using the OxyELISA oxidized protein kit (Millipore). Caspase-3 activation, poly(ADP-ribose)polymerase (PARP) cleavage, and HSP90 fragmentation were detected in whole lysates by Western blot analysis. Results: DC (300 μM) induced the oxidative modification of proteins and increased carbonyl levels to 1.15 ± 0.02 and 2.05± 0.15 nmoles carbonyls/mg protein after 2 and 4 hours of treatment as compared to 0.25 ± 0.01 nmoles carbonyls/mg protein in untreated cells (p< 0.001). Significant increase of oxidative status of proteins correlated with HSP90 cleavage to the 45 KDa fragment, caspase-3 activation and PARP cleavage. Antioxidants significantly inhibited the DC-induced carbonyl production (NAC 90.2 %, Q 46.3 %, VitC 43.9 %) as well as HSP90 degradation and caspase-3 activation. HSP90 processing was not dependent on proteasome activation since none of selected proteasome inhibitors protected HSP90 from cleavage. Conclusion: These results demonstrate that DC-induced degradation of HSP90 to a 45 KDa fragment is mediated through a mechanism involving ROS production, but is not dependent on proteasome activation. ROS-mediated inhibition of HSP90 chaperoning ability is essential for activation of pro-apoptotic signaling in AGS cells exposed to DC.
AGA Abstracts
Advanced Colorectal Neoplasia is Associated With Telomere Shortening Within the Normal Colorectal Mucosa Daniel L. Worthley, Nathan O'Callaghan, Shuji Ogino, Natsumi Irahara, Vicki L. Whitehall, Barbara A. Leggett, Michael Fenech Introduction: In carcinogenesis, telomere shortening can promote chromosomal instability (CIN). Advanced adenomas are the pathological precursors to CIN-pathway colorectal cancers (CRC). Telomere shortening is evident within advanced colorectal adenomas. This study investigated whether telomere attrition was present in the normal colorectal mucosa in patients diagnosed with advanced colorectal neoplasia. Methods: Seventy-one patients were prospectively studied. Colonoscopic biopsies were taken from normal mucosa within the cecum, transverse colon, sigmoid colon and rectum. Telomere length was determined in each biopsy using a quantitative real-time PCR technique. Telomere lengths (kb/diploid genome) were reported for each site as well as for the proximal (mean of cecum and transverse), distal (mean of sigmoid and rectum) and entire colorectum (pancolorectal, mean of all 4 sites). These results were log transformed and examined for univariate and multivariate associations with colorectal region, patient age, smoking and the presence of advanced neoplasia (>10mm, high-grade dysplasia or villous change). Results: 34 patients had normal colonoscopies, 13 had simple adenomas, 9 had advanced neoplasia (8 advanced adenomas and 1 cancer) and 15 had non-adenomatous polyps. Mean age was 59 years (range 28 - 80 years). The mean pancolorectal telomere length was 768 kb/diploid genome. Patients with advanced colorectal neoplasia had significantly shorter telomeres in their background normal mucosa than those without advanced neoplasia, 672 vs. 781 kb/diploid genome, p=0.024. On simple logistic regression pancolorectal telomere length was significantly and inversely associated with the presence of advanced neoplasia, OR=0.010, p=0.031. There was no significant relationship between colorectal region and telomere length, distal vs. proximal mucosal telomere length was 748 vs. 786 kb/diploid genome, p=0.14. In this study there was no clear relationship between age and telomere length. On multivariate logistic regression, using a model that included significant family history, prior adenomas and age, pancolorectal telomere length was independently and inversely associated with the presence of advanced adenomas (OR = 0.002, p = 0.027). Conclusions: Telomere length in the normal colorectal mucosa is an independent predictor of advanced colorectal neoplasia. Telomere attrition in the colorectal field may be an important indicator of, or even prelude to, advanced colorectal neoplasia.
W1740 Anti-Cancer Effects of Xanthorrhizol and Astaxanthine in Esophageal Cancer Cell Lines Moon Kyung Joo, Jong-Jae Park, Beom Jae Lee, Jong Yeol Kim, Jin Ki Hwang, Seung Goun Hong, Keyhyeon Kim, Ja In Park, Joo Yeon Oh, Ji Hoon Kim, Jong Eun Yeon, Jae Seon Kim, Kwan Soo Byun, Young-Tae Bak, Sun-Joong Kim, Seok-Keun Choi Background: Xanthorrhizol (XT) is a natural sesquiterpenoid compound isolated from the rhizome of Curcuma xanthorrhizza Roxb (Zingerberaceae). Recent In Vitro studies support the role of XT as an anti-cancer agent in hepatoma or breast cancer cell lines. Astaxanthin (AX) and α-tocopherol (AT) also have shown anti-cancer effects on various gastrointestinal cancer cell lines. We assessed the effect of XT as well as combination including AX and AT on human esophageal squamous cancer cell lines to show the mechanism of anti-cancer effect and its therapeutic potential. Materials and methods: Two human esophageal squamous cancer cell lines (TE-1, TE-4) were exposed to XT, AX and AT. Quantification of proliferation was performed by MTT assay. After deciding adequate concentration of these agents and treating them for 24 hours, western blot analysis was done do investigate the protein expression of p-p38, p-AKT, cyclin D1, p27 and caspase-3. Results: More than 50% inhibition of cell proliferation by XT by a dose-dependent manner was observed in both cell lines, and similar pattern by AX and AT in TE-4 cell line. Western blot analyses demonstrated that XT alone reduced the protein expression of p-AKT and cyclin D1 in both cell lines. Double combination of XT and AX, and triple combination of XT, AX and AT also reduced the expression of p-AKT and cyclin D1, and increased that of caspase-3 more prominently than XT as a single agent in both cell lines. Conclusion: XT is effective in inhibition of cell proliferation and thought to modulate oncogenic pathway by p-AKT and cyclin D1. Our results also suggest that combination of XT and other anti-cancer agents has cooperative inhibitory effect on the apoptosis of human esophageal squmous cancer cell lines.
W1738 Role of TLR4 in Carcinogenesis and Tumor Progression of Colorectal Cancer Noha E. El-Sakka, Georgina L. Hold, Emad El-Omar Background: There is now a clear association between chronic inflammation and carcinogenesis. Inflammation is accompanied by generation of free radicals, cytokines, and growth factors that favour carcinogenesis by stimulating angiogenesis, and inducing cell proliferation. Toll-like receptor 4 (TLR4) is the main receptor involved in recognition of bacterial endotoxin (LPS) and promotes immunoinflammatory responses by intestinal epithelial cells. TLR4 has a role in promoting tumor growth and carcinogenesis and is a potential therapeutic target in cancer therapy. Blockade of TLR4 signalling in other cancer models is associated with retarded tumour growth and prolonged survival. However little is currently known within the context of CRC. Aim: To examine the pathophysiologic role of TLR4 in CRC carcinogenesis. Methods: Pre-designed silencer siRNA for TLR4 was used to transfect the human CRC cell line SW480. Following siRNA, cells were stimulated with E. coli LPS (2 μg/ml) and various markers of carcinogenesis were compared between wildtype and TLR4 knockdown SW480 cells. For cell proliferation, colorimetric CellTiter 96 AQueous One assay was used to measure formazan product. Apoptosis assessment was performed by Annexin-V-FLUOS using FACSCalibur. A panel of 5 cytokines (IL-8, IL-6, IL-10, IL-1β and TNF-α) were also measured. Mann-Whitney U test was used and p-values < 0.05 were considered statistically significant. Results: Following LPS stimulation of SW480 cells we were able to demonstrate effective TLR4 knockdown following siRNA incorporation. There was a significant reduction in LPS-stimulated cell proliferation: TLR4 siRNA transfection 88.5 (range - 84.1 -91.5) compared to 95.6 (range - 88.9-121.2) for non-transfection, (p =0.003). Apoptosis assessment showed that cells with siRNA/silenced TLR4 had significantly higher percentages of apoptotic cells compared to no siRNA/high TLR4: 14.7% (range - 7.4-16.8%) vs 6.8% (range - 4.0412.8%)(p=0.0028). TLR4 siRNA transfected cells expressed lower IL-6 protein levels at 6 hours compared to normal cells: 1.38pg/ml (range 1.13-1.69) vs 1.75pg/ml (range 1.094.9) (p= 0.04)). Conclusions: Our results suggest that blockade of TLR4 leads to a reduction in tumour cell proliferation, an increase in tumour cell death and a reduction in proinflammatory cytokine production. It remains to be shown whether similar effects could be achieved In Vivo and further work is required to elucidate the molecular mechanisms involved. However, the prospect of achieving these effects offers an opportunity for therapeutic intervention in the context of CRC.
W1741 Effect of Trastuzumab on Phosphorylated Histone H2AX Induced by Topoisomerase-1 Inhibitor (SN-38) in Gastric Cancer Cell Lines With or Without HER2 Expression Mihoko Yamade, Takahisa Furuta, Mitsushige Sugimoto, Chise Kodaira, Masafumi Nishino, Takahiro Uotani, Mutsuhiro Ikuma Aim: Molecular targeting therapy is an important strategy in treating various cancers. Human epidermal growth factor receptor 2 (HER2), a member of the epidermal growth factor receptor family, is a target of such therapeutic strategies and is sometimes found expressed on gastric cancer cells. Recent In Vitro and In Vivo studies have demonstrated that trastuzumab enhances the therapeutic efficacy of antineoplastic agents in treating gastric cancer. Trastuzumab inhibits the signaling pathway from the HER2 receptor and induces antibody-dependent cell-mediated cytotoxicity (ADCC). However, the mechanism by which trastuzumab enhances the cellular toxicity of antineoplastic agents has not been fully elucidated. When a topoisomerase I inhibitor such as SN-38 induces a DNA double strand breaks (DSBs) in cells, histone H2AX is immediately phosphorylated to γH2AX, the sensitive marker of DSBs. Here, we investigated the effect of trastuzumab on SN-38-induced γH2AX in cells with or without HER2 expression. Methods: Gastric cancer cell lines used in the present study were NCI-N87, with strong expression of HER2, and MKN74, which lacks HER2 expression. Both cell lines were exposed to SN-38 with and without trastuzumab, and induction of γH2AX was determined by immunofluorescence and Western blot. The influence of trastuzumab on the cytotoxic effects of SN-38 was measured by MTT and cell count assays, and the effect of trastuzumab on cell cycle progression was determined by flow cytometry. Results: Trastuzumab administered alone induced γH2AX in NCI-N87 cells, but not in MKN74 cells. Further, when administered after SN-38, trastuzumab increased γH2AX induced by SN-38 and enhanced the cytotoxic effect of SN-38 in NCI-N87 cells, but not in MKN74 cells. However, when administered before SN-38, trastuzumab instead reduced γH2AX induction by SN-38 in a dose dependent manner in NCI-N87 cells, but exerted no effect in MKN74 cells. Trastuzumab administered at any check point induced S phase delay in NCI-N87 cells, but not in MKN74 cells. Conclusion: Results from the present study suggest that trastuzumab disrupts the repair of DSBs induced by SN-38 in an HER2-dependent manner. However, trastuzumab also hinders cell cycle progression, which thereby diminishes the replication-dependent generation of DSBs by SN-38. Therefore, whether or not trastuzumab enhances the cytotoxicity of SN-38 depends on the order of administration of SN-38 and trastuzumab.
W1739 ROS-Dependent Degradation of HSP90 in Deoxycholate-Induced Apoptosis in Gastric Cancer Epithelial Cells Maria J. Redlak, Thomas A. Miller Introduction: Heat shock protein 90 (HSP90) is essential for correct protein folding and assembly of some critical proteins which are important for cell survival. In many cancer cells HSP90 is over-expressed and participates in malignant transformation through stabilization of mutated genes and enhancement of cancer cell survival. We have previously shown that deoxycholate (DC) inhibits pro-survival PI3K/Akt/HSP90 signaling in gastric cancer mucosal cells by dephosphorylation of Akt and degradation of HSP90 to a 45 KDa fragment. It has been reported that the chaperoning function of HSP90 may be disrupted by cleavage induced by hydrogen peroxide or other reactive oxygen species (ROS). We examined the hypothesis that HSP90 degradation is mediated by ROS production in gastric cancer cells exposed to deoxycholate. Methods: AGS cells (human gastric adenocarcinoma mucosal cells) received
AGA Abstracts
S-730