• The Korean Journal of Physiology and Pharmacology
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• v.28 no.4
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• pp.379-387
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• 2024

Breast cancer (BC) is most commonly diagnosed worldwide. Liquiritigenin is a flavonoid found in various species of the Glycyrrhiza genus, showing anti-tumor activity. This article was to explore the influences of liquiritigenin on the biological behaviors of BC cells and its underlying mechanism. BC cells were treated with liquiritigenin alone or transfected with oe-HSP90 before liquiritigenin treatment. RT-qPCR and Western blotting were employed to examine the levels of HSP90, Snail, E-cadherin, HSC70, and LAMP-2A. Cell viability, proliferation, migration, and invasion were evaluated by performing MTT, colony formation, scratch, and Transwell assays, respectively. Liquiritigenin treatment reduced HSP90 and Snail levels and enhanced E-cadherin expression as well as inhibiting the proliferation, migration, and invasion of BC cells. Moreover, liquiritigenin treatment decreased the expression of HSC70 and LAMP-2A, proteins related to chaperone-mediated autophagy (CMA). HSP90 overexpression promoted the CMA, invasion, and migration of BC cells under liquiritigenin treatment. Liquiritigenin inhibits HSP90-mediated CMA, thereby suppressing BC cell growth.

• The Journal of Korean Physical Therapy
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• v.26 no.6
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• pp.418-424
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• 2014

Purpose: This study was performed to investigate the effect of joint mobilization on pain relief and cartilage repair in an induced osteoarthritis rat model by analyzing the expression of heat shock protein 70 in articular cartilage. Methods: MIA was injected into SD rats to induce osteoarthritis. These rats were divided into 4 groups: control group (n=30), no further treatment after the MIA injection ; experimental group I(n=30), performed swimming exercise after the MIA injection experimental group II (n=30), underwent joint mobilization after the MIA injection and experimental group III (n=30), performed swimming exercise and underwent joint mobilization after the MIA injection. For the histologic and pathophysiologic evaluation, safranin-O staining and for the immunohistochemical evaluation, the expression of HSP 70 in articular cartilage was analyzed 1, 7, 14, and 21 days after the MIA injection. Results: The inflammatory response and loss of tissue declined in experimental groups I and II over time, whereas the greatest decreases were noted in experimental group III. In the articular cartilage, low expression of HSP 70 was observed in every group on day 1, whereas HSP 70 expression was elevated on days 7 and 14 in experimental groups II and III. After 21 days, experimental group II displayed the strongest positive reaction, whereas HSP 70 was higher in experimental group III at this time point compared to that after 14 days. Conclusion: Our results showed that swimming exercise and joint mobilization had positive effects on pain relief and histologic and functional recovery in an induced osteoarthritis rat model.

• Journal of Life Science
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• v.27 no.3
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• pp.267-274
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• 2017

The patient with end-stage renal disease show several nervous complications. The factors contributing to the nervous complications are still incompletely characterized. Cyanate, known as one of the uremic toxins, is derived spontaneously from urea. To investigate the mechanism of cyanate-induced effect on C6 glioma cells, the glioma cells were treated with 0, 1, 5, 10, 20 and 40 mM cyanate. There was a dose-dependent decrease in cell viability and the decreased number of cell was observed in glioma cells by treatment with cyanate. Western blot showed the down- regulation of procaspase-3, which means up-regulation of caspase-3, and the up-regulation of caspase-8, but the down-regulation by cyanate. In addition, cDNA microarray showed 934 down-regulated genes and 165 up-regulated genes on 1,099 genes in cyanate treated group. Treatment with cyanate led to 16 down-regulated genes and 6 up-regulated genes on apoptosis category, and especially heat shock 70 kD protein 1A gene on the category of apoptosis was significantly up-regulated. These results suggest that cyanate can induce apoptosis through caspase-8 and caspase-3 in glioma cells and decrease of gene expression including apoptosis category in glioma cells. These effects of cyanate may play a role in the nervous complications of patient with end-stage renal disease.

• Journal of Life Science
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• v.28 no.10
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• pp.1212-1219
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• 2018

The critical role of heat shock protein 90 (Hsp90) in tumorigenesis led to the development of several first- and second-generation Hsp90 inhibitors, which have demonstrated promising responses in cancers. In this study, we found second-generation Hsp90 inhibitor BIIB021-resistant multidrug-resistant (MDR) human cancer cells, although BIIB021 was shown to be active in first-generation Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG)-resistant MDR cells. MCF7-MDR and HeyA8- MDR cells were more resistant to BIIB021 than their parental counterparts, indicating that BIIB021 cannot be applicable to all cancer cells expressing MDR proteins. We revealed that dimethyl-celecoxib (DMC), one of the non-steroidal anti-inflammatory drugs (NSAIDs), potentiated cytotoxicity of BIIB021 against both BIIB021-resistant and BIIB021-sensitive MDR cells. The effectiveness of NSAIDs involving celecoxib and DMC in combination with BIIB021 led to the autophagic degradation/down-regulation of mutant p53 (mutp53) that overexpressed MDR cells and the suppression of Hsp70 induction. This resulted in sensitization of MDR cells to BIIB021. Moreover, autophagy induction by sulindac sulfide, another type of NSAID, and niclosamide, an FDA-approved anthelmintic drug, potentiated 17-AAG-mediated autophagic degradation/down-regulation of mutp53 and c-Myc, client proteins of Hsp90. Therefore, our results suggest that NSAIDs and niclosamide positively enhance the anticancer activity of Hsp90 inhibitors through an autophagic pathway. They may also be new candidates for sensitizing MDR cells to Hsp90 inhibitors.

• Clinical and Experimental Reproductive Medicine
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• v.26 no.1
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• pp.103-109
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• 1999

Objective: Heat shock protein 70-2 (Hsp70-2) gene knockout mice are found to have premeiotic arrest at the primary spermatocyte stage with a complete absence of spermatids and spermatozoa. This observation led to the hypothesis that hspA2 may be disrupted in human testes with abnormal spermatogenesis. To test this hypothesis, we studied the mRNA expression of hspA2 in infertile men with azoospermia. Design: The mRNA expression were analyzed by competitive RT-PCR among testes with normal spermatogenesis, pachytene spermatocyte arrest, and sertoli-cell only syndrome. Materials and methods: Testicular biopsy was performed in men with azoospermia (n=15). Specimens were subdivided into three groups: (group 1) normal spermatogenesis (n=5), (group 2) spermatocyte arrest (n=5), (group 3) Sertoli-cell only syndrome (n=5). Total RNA was extracted by Trizol reagent. Total extracted RNA was reverse transcribed into cDNA and amplified by PCR using specific primers for hspA2 target cDNAs. A competitive cDNA fragment was constructed by deleting a defined fragment from the target cDNA sequence, and then coamplified with the target cDNA for competitive PCR. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene was used as an internal control. Results: On Competitive RT-PCR analyses for hspA2 mRNA, significant amount of hspA2 expression was observed in group 1, whereas a constitutively low level of hspA2 was expressed in groups 2 and 3. Conclusion(s): The study demonstrates that the hspA2 gene expression is down-regulated in human testes with abnormal spermatogenesis, which in turn suggests that hspA2 gene may play a specific role during meiosis in human testes.

• Journal of Pharmacopuncture
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• v.3 no.2
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• pp.191-212
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• 2000

Objective: This study was perfomled to examine the therapeutic effect of aqua-acupuncture solution of Hominis Placenta(HP) on kidney and liver intoxicated by $HgCI_2$ in rats. Methods: $10\%$ and $25\%$ HP aqua-acupuncture were carried out everyday for 8 days on corresponding bilateral loci of Shinsu(BL23) and Kansu(BL18), respectively, after mercuric chloride intoxication in rats. Thereafter BUN, creatinine, GOT, GPT, ALP, ${\gamma}$-GT, albumin and total bilirubin were measured before intoxication, and at the 4th and the 8th experimental day. Histopathological and immunochemical observation were also carried out. Results: 1. It showed significant decreases of BUN in the group of $10\%$ HP aqua-acupuncture into Shinsu on the 4th experimental day as compared with the control group. 2. It showed significant decreases of creatinine in the group of $10\%$ HP aqua-acupuncture into Shinsu on the 4th and the 8th experimental days as compared with the control group. 3. There were not any significant changes of GOT, GPT, ALP,${\gamma}$-GT, albumin and total bilirubin in the HP aqua-acupuncture groups compared with the control group. 4. By the histopathological observations on kidney under a light microscope, alt the $10\%$ and $25\%$ HP aqua-acupuncture into Shinsu showed the preventive effect on tubulo-interstitial necrosis and muItifocal calcification in tubular lumen respectively compared with the control group. 5. By the histopathological observations on liver under a light mIcroscope, the groups $10\%$ and $25\%$ HP aqua--acupuncture into Kansu did not show any significant changes in the liver compared with the control group. 6. By the immunochemical analysis of heat shock protein(hsp) and glucose-regulated protein(grp) in rat renal cortex, the expressions of hsp70 and grp78 were decreased in the $10\%$ and $25\%$ HP aqua-acupuncture into Shinsu respectively compared with the control group. Conclusion: These results suggest that Hominis Placenta aqua-acupuncture have an effect on prevention and protection of renal intoxication by $HgCI_2$ in rats.

• Reproductive and Developmental Biology
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• v.38 no.1
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• pp.53-62
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• 2014

The objective of this study was to investigate the relationship between fertility and protein pattern change using in vitro fertilization, analysis of sperm characteristics and two-dimensional gel electrophoresis in different pig types. In results, the viability and mitochondria integrity of sperm were higher significantly (p<0.05) but the portions of acrosome reaction was lower significantly (p<0.05) in Duroc and $F_1$ (potbellied ${\times}$ PWG miniature pig) than PWG miniature. On in vitro fertilization to investigate fertility, the fertility of $F_1$ semen war higher significantly (p<0.05) than in Duroc and PWG miniature pig. On the other hand, protein patterns showed similar function among the different boar semen. Especially, the heat shock 70 kDa 1-like and G patch domain-containing protein 4 were significantly (p<0.05) higher expressed in $F_1$ than in Duroc and PWG miniature pig. The proteins associated with mitochondria in Duroc were significantly (p<0.05) higher expressed than in $F_1$ and PWG miniature pig. The developmental rates to blastocyst stage of oocytes fertilized with sperm of $F_1$ pig were significantly (p<0.05) higher than in PWG miniature pig. However, phosphoglycerate kinase 2 and zinc finger protein 431 were significantly (p<0.05) higher expressed in PWG miniature pig than in $F_1$ and Duroc pigs. In conclusion, the results of the present study indicate that different proteins were expressed in different pig types, and were associated with a sperm functions and embryo development.

• Journal of Life Science
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• v.24 no.2
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• pp.105-111
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• 2014

The purpose of this study was to characterize equine heat-shock protein (Hsp) genes and analyze their expression pattern in various horse tissues and blood leukocytes after exercise. In a previous study, RNA sequencing of blood and skeletal muscles of thoroughbreds before and after exercise was performed using differently expressed gene (DEG) analysis. Three Hsp genes (HspH1, Hsp90${\alpha}$ and Hsp70) were selected by DEG analysis and were found to be differentially expressed in either blood or muscle. To validate and extend previous observations on these genes, we performed RT-PCR analyses of horse tissue as well as real-time qPCR analyses of blood leukocytes after exercise. mRNA expression of these Hsp genes was found to be ubiquitous in the analyzed tissues (including thyroid, colon, skeletal muscle, cecum, kidney, spinal cord, heart, and lung). In addition, Hsp mRNA expression of these genes in extracted whole blood increased after 120 minutes of exercise compared to the baseline condition. These results are in agreement with the results of human and other experimental animals, suggesting that regulatory mechanisms that are responsible for upregulation of Hsp gene transcription may be conserved among species. Further investigations to correlate Hsp gene expression patterns with athletic performance or recovery processes after exercise are warranted.

• Physical Therapy Korea
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• v.13 no.3
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• pp.57-66
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• 2006

Ischemic stroke results from a transient or permanent reduction in cerebral blood flow that is restricted to the territory of a major brain artery. Thus, this study was performed to examine (1) the effects of swimming exercise on the improvement of muscle atrophy, and (2) exercise and HSP 70 expression in an ischemic stroke model induced by middle cerebral artery occlusion. The results of this study were as follows: One week after ischemic stroke was induced, changes appeared in the muscle weight of the gastrocnemius muscle due to muscle atrophy in the affected side. Group II showed statistically significant difference from group III eight weeks after ischemic stroke was induced. (p<.05). One week and eight weeks after ischemic stroke was induced there was significant decrease in the relative muscle weight of the gastrocnemius muscle in each group except Group IV, while there was statistically significant increase in group II eight weeks after ischemic stroke was induced, compared to group III (p<.05). For neurologic exercise behavior tests, Group II generally had the highest score, compared to other groups. In immunohistochemical observations, Group II showed a decrease in HSP 70. The above results suggest that swimming exercise improved muscle atrophy, changed the HSP 70 expression of ischemic stroke in rats, and contributed to the improvement of exercise function.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6011-6016
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• 2012

Introduction: Epidemiological studies suggest a protective role for ${\beta}$-carotene with several malignancies. Esophageal adenocarcinoma frequently arises from Barrett's esophagus (BE). We postulated that ${\beta}$-carotene therapy maybe protective in BE. Materials and Method: We conducted a prospective study in which 25 mg of ${\beta}$-carotene was administered daily for six-months to six patients. Each patient underwent upper endoscopy before and after therapy and multiple mucosal biopsies were obtained. Additionally, patients completed a gastroesophageal reflux disease (GERD) symptoms questionnaire before and after therapy and severity score was calculated. To study the effect of ${\beta}$-carotene at molecular level, tissue extracts of the esophageal mucosal biopsy were subjected to assessment of heat-shock protein 70 (HSP70). Results: A significant (p<0.05) reduction in mean GERD symptoms severity score from $7.0{\pm}2.4$ to $2.7{\pm}1.7$ following ${\beta}$-carotene therapy was noted. Measurement of Barrett's segment also revealed a significant reduction in mean length after therapy. In fact, two patients had complete disappearance of intestinal metaplasia. Furthermore, marked enhancement of HSP70 expression was demonstrated in biopsy specimens from Barrett's epithelium in four cases that were tested. Conclusions: Long-term ${\beta}$-carotene therapy realizes amelioration of GERD symptoms along with restitution of the histological and molecular changes in esophageal mucosa of patients with BE, associated with concurrent increase in mucosal HSP70 expression.