• Title/Summary/Keyword: G2 cell cycle arrest

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Apoptotic Effect of Ethanol Extracts of Bojungbangamtang and Acidic Polysaccharide of Korea Red Ginseng in a MCF7/adR Multidrug-resistance Breast Cancer Cells (항암제 내성 유방암 MCF7/adR 세포주에 대한 보정방암탕과 홍삼산성다당체의 세포고사 유도효과)

  • Ahn, Gyu-In;Park, Cheol-Hwan;Lee, Eun-Ok;Lee, Hyo-Jung;Lee, Jae-Ho;Kim, Kwan-Hyun;Rhee, Yun-Hee;Jang, Yu-Sung;Kim, Sang-Tae;Kim, Sung-Hoon
    • YAKHAK HOEJI
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    • v.50 no.4
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    • pp.272-277
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    • 2006
  • This study was undertaken to determine whether the 9 herbal complex induces apoptosis in human breast cancer MCF-7 cells and adriamycin-resistant MCF7/adR cells. Ethanol extracts of Bojungbangamtang (BBTE) and acidic polysaccharide of Red Ginseng (GIN) induced cell death in both MCF-7 and MCF7/adR cells. Ethanol extracts of Bojungbangamtang and acidic polysaccharide of Red Ginseng also induced $G_2/M$ cell cycle arrest and increased TUNEL positive cells in MCF7/adR cells. In addition, flow cytometric analysis revealed the decreased expression of P-glycoprotein (P-gp) in ethanol extracts of Bojungbangamtang and acidic polysaccharide of Red Ginseng treated MCF7/adR cells. Similarly, decreased protein levels of P-glycoprotein and multidrug resistance associated proteins-1 were also determined by immunocytometry in ethanol extracts of Bojungbangamtang treated MCF7/adR cells. Taken together these data indicate that ethanol extracts of Bojungbangamtang and acidic polysaccharide of Red Ginseng inhibit the function of ABC transporters such as multi drug resistance associated proteins (MRPs) and P-glycoprotein as well as induce apoptosis in MCF7/adR cells. Thus, these data suggest that ethanol extracts of Bojungbangamtang and polysaccharide of Red Ginseng can be candidates for the treatment of multidrug-resistant MCF7/adR cells.

Menadione Induced Apoptosis in MKN45 Cells via Down-regulation of Survivin (Menadione의 Survivin 하향 조절을 통한 MKN45 세포의 세포사멸 유도 효과)

  • Lee, Min Ho;Kim, Jeongyong;Cho, Yoonjung;Kim, Do Hyun;Yang, Ji Yeong;Kwon, Hye Jin;Park, Min;Woo, Hyun Jun;Kim, Sa-Hyun;Kim, Jong-Bae
    • Korean Journal of Clinical Laboratory Science
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    • v.51 no.1
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    • pp.71-77
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    • 2019
  • Menadione is known as an anti-tumor factor. Many studies have reported the potential anti-cancer role of menadione against a range of cancer cell lines. In this study, the anti-cancer effects of menadione and the underlying molecular signaling involved in apoptosis was investigated in gastric cancer cell lines. The menadione treatment decreased the cell viability of MKN45 gastric cancer cells. The decreased cell viability was attributed to the induction of apoptosis, which was confirmed by the results indicating the activation of caspase-3 and -7 and the cleavage of PARP in Western blotting. The upstream regulatory molecules involved in apoptosis were investigated further and it was discovered that menadione reduced the expression of survivin, an inhibitor of upstream apoptosis proteins. In addition, a transcription factor ${\beta}$-catenin, which is known to regulate survivin expression, was down-regulated by menadione. A previous report showed that menadione inhibited XIAP expression to induce apoptosis and induced G2/M cell cycle arrest in AGS cells. This study elucidated another inhibitory mechanism of menadione against gastric cancer cells in a different cell line. Although further studies will be needed, the inhibitory mechanism demonstrated in this study will help better understand the anti-cancer effects of menadione.

Immunohistochemical Study of Phosphatase and Tensin Homolog Deleted on Chromosome Ten in Gefitinib Treated Nonsmall Cell Lung Cancer Patients (폐암 조직에서의 PTEN 발현 정도와 Gefitinib의 반응율과의 관계)

  • Lee, Sung Yong;Lee, Ju Han;Jung, Jin Yong;Lee, Kyoung Ju;Lee, Seung Hyeun;Kim, Se Joong;Lee, Eun Joo;Hur, Gyu Young;Jung, Ki Hwan;Jung, Hye Cheol;Lee, Sang Yeub;Kim, Je Hyeong;Shin, Chol;Shim, Jae Jeong;In, Kwang Ho;Kang, Kyung Ho;Yoo, Se Hwa
    • Tuberculosis and Respiratory Diseases
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    • v.58 no.5
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    • pp.473-479
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    • 2005
  • Background : Gefitinib targets the epidermal growth factor receptor r(EGFR), and Gefitinib has antitumor activity in patient with non-small cell lung cancer (NSCLC). However, only 10 to 20 percent of patients show a clinical response to this drug, and the molecular mechanisms underlying patient sensitivity to gefitinib are unknown. PTEN (Phosphatase and tensin homolog deleted on chromosome Ten) plays a role for the modulation of the phosphatidylinositol 3-kinase pathway (PI3K), which is involved in cell proliferation and survival, so that it can inhibit cell cycle progression and induce G1 arrest. Therefore, we analyzed the relationship between PTEN expression and gefitinib's responsiveness in patients having advanced non small cell lung cancer that had progressed after previous chemotherapy. Methods : The expression of PTEN was studied by immunohistochemistry in paraffin-embedded tumor blocks that were obtained from 22 patients who had been treated with gefitinib from JAN, 2001 to AUG. 2004. For the evaluation of the relationships between the PTEN expression, the clinical stage and the basal characteristics, those cases that showed the respective antigen expression in >50% of the tumor cells were considered positive. Results : The positive rate of PTEN staining was 55% of the total of 22 patients. There was a significant relationship between the increased expression of PTEN and the response group (p=0.039). However, there was no significant relationship between the expression of PTEN and other clinicopathologic characteristics. Conclusion: The expression of PTEN in patients with advanced non small cell lung cancer that has progressed after previous chemotherapy may play a role in gefitinib's responsiveness.

Clinical Analysis According to $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ Expression in Gastric Cancer (위암에서의 $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ 단백 발현)

  • Kim, Sin-Sun;Park, Yong-Geun;Jun, Kyong-Hwa;Jung, Hun;Song, Gyo-Young;Kim, Jin-Joo;Chin, Hyung-Min;Kim, Wook;Park, Cho-Hyun;Park, Seung-Man;Lim, Keun-Woo;Kim, Seung-Nam;Jeon, Hae-Myung
    • Journal of Gastric Cancer
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    • v.6 no.1
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    • pp.36-42
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    • 2006
  • Purpose: The $p21^{Waf1/Cip1}$ protein Inhibits the cell cycle by Inhibiting the phosphorylation at the $G1{\rightarrow}S$ check point, and the $p27^{kip1}$ protein similarly performs the suppressor function by controlling the p27-mediated G1 arrest. In this study, we analysed the clinical status and survival rates in correlations with p21 and p27 expression patterns in gastric cancer. Materials and Methods: Between 1993 and 1997, 192 patients who underwent surgeries in Catholic Medical Center were analysed retrospectively in this study. Immunohistochemical staining was performed and if the nuclei of the tumor cells were stained, we assumed those as positive results. Statistical analysis was based on clinicopathological findings and differences in survival rates. Results: The expression rate of p27 was 28.1% and 15.6% in p21 each. The ratio of T1-2(80.0%) was significantly high in p21 (+), but the ratio of T3-4 (50.6%) was slightly high in p21 (-). There was no statistical significance regarding other factors. The results in p27 was not much different from expression rate of p21 in T-stage. In addition, p27 expression in diffuse type (91.3%) was higher than in intestinal type (62.7%) by Lauren's classification (P<0.05). Also, there was no statistical significance in other factors. In the correlation of p21 and p27, p27 was positive when p21 was positive (53.5%). Conversely, p27 was negative when p21 was negative (76.5%, p<0.05). In the p21 and p27 combination test, there was higher rate of T1-2 (87.5%) in p21 (+)/p27 (+), and higher rate of T3-4 (58.1%) in p21 (-)/p27 (-) (P<0.05). Results showed higher rate of intestinal type (100%) in p21 (+)/p27 (+), and diffuse type (87.0%) was dominant in p21 (-)/p27 (-) (P<0.05) by Lauren's classification. Moreover, there was no statistical significance in the 5-year survival rate in the expression of p21 and p27, and the 5-year survival rate was highest in the case of p21 (+)/p27 (+) without statistical significance. Conclusion: In our study, $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ expressed similar patterns. The expression of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ affected the degree of invasiveness of the tumor, and. Combined examination result revealed the correlation of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ with Lauren's classification and depth of invasion of the tumor. However, we assumed that little difference between the survival rates depending on expression of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ has limited their value as predictable prognostic indicators.

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