• 동의생리병리학회지
• /
• 제19권5호
• /
• pp.1370-1374
• /
• 2005

The Tosyl-JM3 (TJM3) is a modified compound from one of 1,2,3,4-Tetra- hydroisoquinoline (THIQ) derivatives. The THIQs include potent cytotoxic agents that display a range of anti-tumor activities, antimicrobial activity, and other biological properties. In this study, we investigated the effect of TJM3 on the cytotoxicity, induction of apoptosis in human promyelocytic leukemia cells (HL-60 cells). TJM3 showed a significant cytotoxic activity in HL-60 cells (IC50 = approximately $60{\mu}g/m{\ell}$) after a 24 hr incubation. Treatment of HL-60 cells with TJM3 exhibited several features of apoptosis, including formation of DNA ladders in agarose gel electrophoresis, morphological changes of HL-60 cells with DAPI stain. Here we observed that TJM3 caused a decrease of procaspase-3 protein. Further molecular analysis demonstrated that TJM3 led to cleavage of poly(ADP-ribose) polymerase (PARP) by western blot and increase of hypodiploid (Sub-G1) population in the flow cytometric analysis. In conclusion, these above results indicate that TJM3 dramatically suppresses HL-60 cell growth and induces apoptosis. These data may support a possibility for the use of TJM3 in the prevention and treatment of leukemia.

• Biomolecules & Therapeutics
• /
• 제23권5호
• /
• pp.471-478
• /
• 2015

Colon cancer is considered as the precarious forms of cancer in many developed countries, with few to no symptoms; the tumor is often diagnosed in the later stages of cancer. Monoterpenes are a major part of plant essential oils found largely in fruits, vegetables and herbs. The cellular and molecular activities show therapeutic progression that may reduce the risk of developing cancer by modulating the factors responsible for colon carcinogenesis. Colon cancer was induced with DMH with a dose of (20 mg/Kg/body weight) for 15 weeks by subcutaneous injection once in a week. Myrtenal treatment was started with (230 mg/Kg/body weight) by intragastric administration, one week prior to DMH induction and continued till the experimental period of 30 weeks. The Invivo results exhibit the elevated antioxidant and lipid peroxidation levels in DMH treated animals. The Histopathological analysis of colon tissues well supported the biochemical alterations and inevitably proves the protective role of Myrtenal. Treatment with myrtenal to cancer bearing animals resulted in a remarkable increase in the inherent antioxidants and excellent modulation in the morphological and physiological nature of the colon tissue. It is thus concluded that myrtenal exhibits excellent free radical scavenging activity and anticancer activity through the suppression of colon carcinoma in Wistar albino rats.

• 한방재활의학과학회지
• /
• 제23권2호
• /
• pp.17-31
• /
• 2013

Objectives : Peripheral nerve injuries are commonly encountered clinical problems and often result in serve functional deficit. Bee venom and scolopendra subspinipes have been traditionally used in oriental medicine to treat several inflammatory diseases and chronic pain conditions. Methods : In the present study, the effects of bee venom pharmacopuncture and scolopendra subspinipes pharmacopuncture on functional recovery, severity of pain, and expressions of neurofilament, cycloxygenease-2(COX-2), and tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) following sciatic crushed nerve injury in rats were investigated. For this study, walking tract analysis, plantar test, western blot for COX-2 and TNF-${\alpha}$, and immunohistochemistry for neurofilament were performed. Results : In the present results, sciatic functional index(SFI) in walking tract analysis was significantly decreased following sciatic crushed nerve injury, and pain severity in plantar test was significantly increased. COX-2 and TNF-${\alpha}$ expressions were increased whereas neurofilament expression was decreased by sciatic crushed nerve injury. On the other hand, bee venom pharmacopuncture and scolopendra subspinipes pharmacopuncture improved SFI in walking tract analysis and suppressed the pain severity in sciatic crushed nerve injury. Bee venom pharmacopuncture and scolopendra subspinipes pharmacopuncture suppressed COX-2 and TNF-${\alpha}$ expression and enhanced the neurofilament expression in sciatic crushed nerve injury. Conclusions : In the present study, we have shown that treatment with bee venom or scolopendra subspinipes is the effective therapeutic modality to ameliorate the symptoms of sciatic crushed nerve injury. The efficacies of bee venom and scolopendra subspinipes were similar.

• 대한한방부인과학회지
• /
• 제19권1호
• /
• pp.125-138
• /
• 2006

Purpose : This study was to investigate the effects of Dohongsamul-tang extract on the rat with an surgically induced endometriosis. Methods : Four weeks after the operation for inducing the endometriosis to a matured female rat, the normal hyperplasia of the transplanted endometrium was identified in anatomico-histological aspects. By dividing each of the control group and Dohongsamul-tang administered experimental group into 8 rats, Dohongsamul-tang concentrates were administered orally to the experimental group with 1g/1ml/200g everyday for 40 days and then images were taken from the macroscopic tissues which were transplanted to the mesenterium, and the concentrations of progesterone, estradiol, tumor necrosis $factor-{\alpha}(TNF-{\alpha})$, and interleukin(IL)(-2, -4, -6, and -10) in the serum were measured. Results : Transplanted endometrium tissues showed the histological findings in accordance with the normal endometrium tissues and from the macroscopic findings the size of transplanted endometrium tissues showed a definite decrease. Compared to the control group, the experimental group showed significant decreases in the values of $TNF-{\alpha}$,IL-2, and IL-4 and significant increases in the values of IL-10. However, there were no significant differences in progesterone, estradiol and IL-6. Conclusion : From the above results, Dohongsamul-tang showed the strengthening of immunological function and anti-inflammatory effect. Therefore it is considered that Dohongsamul-tang will be very effective on the treatment of inflammation developed endometriosis, especially to treat the endometriosis without affecting the ovary functions.

• The Korean Journal of Physiology and Pharmacology
• /
• 제20권4호
• /
• pp.357-366
• /
• 2016

Pro-inflammatory cytokine and brain-derived neurotrophic factor (BDNF) are modulated in post-traumatic stress disorder (PTSD). This study investigated the effects of ibuprofen (IBU) on enhanced anxiety in a rat model of PTSD induced by a single prolonged stress (SPS) procedure. The effects of IBU on inflammation and BDNF modulation in the hippocampus and the mechanisms underlying for anxiolytic action of IBU were also investigated. Male Sprague-Dawley rats were given IBU (20 or 40 mg/kg, i.p., once daily) for 14 days. Daily IBU (40 mg/kg) administration significantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index in the EPM test, and increased the time spent in the center of an open field after SPS. IBU administration significantly decreased the expression of pro-inflammatory mediators, such as tumor necrosis $factor-{\alpha}$, $interleukin-1{\beta}$, and BDNF, in the hippocampus, as assessed by reverse transcription-polymerase chain reaction analysis and immunohistochemistry. These findings suggest that IBU exerts a therapeutic effect on PTSD that might be at least partially mediated by alleviation of anxiety symptoms due to its anti-inflammatory activity and BDNF expression in the rat brain.

• Child Health Nursing Research
• /
• 제7권1호
• /
• pp.108-117
• /
• 2001

This research objected to the diagnosed patients as acute lymphoblastic leukemia, acute myelogenous leukemia, neuroblastoma, non-Hodgkins lymphoma, Hodgkin's disease, kidney tumor, myelodysplastic syndrom and juvenile chronic leukemia after admission in the 'P' hospital in Pusan from Aug. 1. 1999 to Jan. 31. 2000. The results of this study are summarized as follows. 1. On the specific character between the experimental(exp.) group and the control (con.) group : there were 7 of 4-7 years old patients(the most) in the experimental group(53.8％), 5 of 12 years old or older patients in the control group (38.5％). Patients who experienced operation were 7 in the exp. group(53.8％) and 6 in con. group(46.2％). The largest number of the patients' diagnosis was acute lymphoblastic leukemia by 5 in the exp. group(38.5％) and 4 in the con. group (30.8％). The hardest nausea came on the second day by 5 in the exp. group(38.5％), 9 in the con. group(69.2％). 2. P-score of the nausea vomiting on the number of daily anticancer drug administration : first day, the exp. group got 9.6 and the con. group 17.6(P = 0.03). 2nd day, 10.9 and 19.4(P = 0.00), 3rd day, 10.6 and 18.3(P = 0.00), 4th day 10.0 and 18.0, 5th day 10.9 and 16.8(P = 0.05). The score showed statistically significant difference(P < .05). 3. Oral intake didn't show statistically significant difference between two groups. However the average of Oral intake of the exp. group was continually higher than the con. group except to the first day after administration. In conclusion, nursing intervention and nutrition care are much more needed on the 2-3th day after administration to reduce nausea vomiting, and for remission of nausea and enlarging oral intake it is utilizable to apply the easy, economic Oral Cryotherapy to the young patients who undergo chemotherapy.

• Journal of Gastric Cancer
• /
• 제3권2호
• /
• pp.75-79
• /
• 2003

Purpose: Evidence exists that dysregulation of apoptosis is involved in the pathogenesis of cancer development. The Bcl-$x_{L}$/Bcl-2-associated death promoter (BAD), a member of the Bcl-2 family, is a critical regulatory component of the intrinsic cell-death pathway that exerts its pro-apoptotic effect upon heterodimerization with anti-apoptotic proteins Bcl-2 and Bcl-$X_{L}$. Expression of the BAD protein has been reported in several cancer types, but not in stomach cancer. The aim of this study was to explore the expression status of the BAD protein in gastric carcinomas. Materials and Methods: In the current study, we analyzed the expression of the BAD protein in 60 advanced gastric adenocarcinomas by using immunohistochemistry and a tissue microarray approach. Results: Immunopositivity (defined as $\geq\30\%$) was observed for the BAD protein in 57 ($95\%$) of the 60 cancers. Normal gastric mucosal cells showed weaker expressions of the BAD protein than gastric carcinomas. Conclusion: Taken together, these results suggest that stomach cancer cells in vivo may need BAD protein expression for apoptosis. Also, the higher expression of the BAD protein in stomach cancer cells than in normal gastric mucosal cells suggests that apoptosis might be easily triggered in susceptible stomach cancer cells, thereby producing selective pressure to make more apoptosis-resistant cells during tumor development.

• Biomolecules & Therapeutics
• /
• 제20권3호
• /
• pp.313-319
• /
• 2012

In recent years, inhibition of HDACs has emerged as a potential strategy to reverse aberrant epigenetic changes associated with cancer, and several classes of HDAC inhibitors have been found to have potent and specific anticancer activities in preclinical studies. But their precise mechanism of action has not been elucidated. In this study, a novel synthetic inhibitor of HDAC, 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide [IN-2001] was examined for its antitumor activity and the underlying molecular mechanisms of any such activity on human breast cancer cell lines. IN-2001 effectively inhibited cellular HDAC activity ($IC_{50}$ = 0.585 nM) inMDA-MB-231 human breast cancer cells. IN-2001 caused a significant dose-dependent inhibition of cell proliferation in estrogen receptor (ER) negative MDA-MB-231human breast cancer cells. Cell cycle analysis revealed that the growth inhibitory effects of IN-2001 might be attributed to cell cycle arrest at $G_0/G_1$ and/or $G_2$/Mphase and subsequent apoptosis in human breast cancer cells. These events are accompanied by modulating several cell cycle and apoptosis regulatory genes such as CDK inhibitors $p21^{WAF1}$ and $p27^{KIP1}$ cyclin D1, and other tumor suppressor genes such as cyclin D2. Collectively, IN-2001 inhibited cell proliferation and induced apoptosis in human breast cancer cells and these findings may provide new therapeutic approaches, combination of antiestrogen together with a HDAC inhibitor, in the hormonal therapy-resistant ER-negative breast cancers. In summary, our data suggest that this histone deacetylase inhibitor, IN-2001, is a novel promising therapeutic agent with potent antitumor effects against human breast cancers.

• Biomolecules & Therapeutics
• /
• 제20권3호
• /
• pp.273-279
• /
• 2012

Hesperidin, a flavanone present in citrus fruits, has been studied as potential therapeutic agents that have anti-tumor activity and apoptotic effects in several cancers, but there is no report about the apoptotic effect of hesperidin in human malignant pleural mesothelioma through the specificity protein 1 (Sp1) protein. We investigated whether hesperidin inhibited cell growth and regulated Sp1 target proteins by suppressing the levels of Sp1 protein in MSTO-211H cells. The $IC_{50}$ value of hesperidin was determined to be 152.3 ${\mu}M$ in MSTO-211H cells for 48 h. Our results suggested that hesperidin (0-160 ${\mu}M$) decreased cell viability, and induced apoptotic cell death. Hesperidin increased Sub-$G_1$ population in MSTO-211H cells. Hesperidin significantly suppressed mRNA/protein level of Sp1 and modulated the expression level of the Sp1 regulatory protein such as p27, p21, cyclin D1, Mcl-1, and survivin in mesothelioma cells. Also, hesperidin induced apoptotic signaling including: cleavages of Bid, caspase-3, and PARP, upregulation of Bax, and down-regulation of Bcl-$_{xl}$ in mesothelioma cells. These results show that hesperidin suppressed mesothelioma cell growth through inhibition of Sp1. In this study, we demonstrated that Sp1 acts as a novel molecular target of hesperidin in human malignant pleural mesothelioma.

• Journal of Dental Anesthesia and Pain Medicine
• /
• 제19권5호
• /
• pp.253-260
• /
• 2019

Background: Sometimes general anesthesia is required for dental surgery in pregnant women. Facial bone fractures or neck abscess should be treated immediately. Dental surgery, however, creates a stressful situation that can cause inflammation. Inflammatory responses are a well-known major cause of preterm labor and preterm birth. Here we demonstrate the effects of remifentanil on the factors related to preterm labor and its mechanism of action on amniotic-derived epithelial cells (WISH cells). Methods: WISH cells were exposed to lipopolysaccharide (LPS) for 24 h and co-treated with various concentrations of remifentanil. MTT assays were performed to measure cell viability. To explain the effects of remifentanil on the factors related to inflammation in WISH cells, activation of nuclear factor kappa B ($NF-{\kappa}B$) and p38 and the expression of interleukin $(IL)-1{\beta}$, tumor necrosis factor $(TNF)-{\alpha}$, cyclooxygenase (COX)2, and prostaglandin E $(PGE)_2$ were quantified using western blotting and RT-PCR, respectively. Results: Remifentanil did not affect WISH cell viability. In western blot analysis, co-treatment with remifentanil resulted in decreased phosphorylation of $NF-{\kappa}B$, and expression of COX2 and $PGE_2$ in LPS-induced inflammation, but the results were statistically significant only at low concentrations. Reduction of $IL-1{\beta}$ and $TNF-{\alpha}$ expression was also observed with RT-PCR. Conclusion: Co-treatment with remifentanil does not affect the viability of WISH cells, but reduces the expression of the factors related to inflammation, which can induce uterine contraction and preterm labor. These findings provide evidence that remifentanil may inhibit uterine contraction and preterm labor in clinical settings.