• BMB Reports
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• 제44권9호
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• pp.572-577
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• 2011

Elevated phospholipase D (PLD) expression prevents cell cycle arrest and apoptosis. However, the roles of PLD isoforms in cell proliferation and apoptosis are incompletely understood. Here, we investigated the physiological significance of the interaction between PLD2 and protein kinase CKII (CKII) in HCT116 human colorectal carcinoma cells. PLD2 interacted with the CKII${\beta}$ subunit in HCT116 cells. The C-terminal domain (residues 578-933) of PLD2 and the N-terminal domain of CKII${\beta}$ were necessary for interaction between the two proteins. PLD2 relocalized CKII${\beta}$ to the plasma membrane area. Overexpression of PLD2 reduced CKII${\beta}$ protein level, whereas knockdown of PLD2 led to an increase in CKII${\beta}$ expression. PLD2-induced CKII${\beta}$ reduction was mediated by ubiquitin-dependent degradation. The C-terminal domain of PLD2 was sufficient for CKII${\beta}$ degradation as the catalytic activity of PLD2 was not required. Taken together, the results indicate that the C-terminal domain of PLD2 can regulate CKII by accelerating CKII${\beta}$ degradation in HCT116 cells.

• 동의생리병리학회지
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• 제19권1호
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• pp.167-173
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• 2005

To investigate the possible molecular mechanism (s) of bee venom as a candidate of anti-cancer drug, we examined the effects of the compound on the growth of human lung carcinoma cell line A549. Bee venom treatment declined the cell growth and viability of A549 cells in a concentration-dependent manner, which was associated with induction of apoptotic cell death. Bee venom down-regulated the levels of anti-apoptotic genes such as Bcl-2 and Bcl-XS/L, however, the levels of Bax, a pro-apoptotic gene, were up-regulated. Bee venom treatment induced not only tumor suppressor p53 but also cyclin-dependent kinase inhibitor p21WAF1/CIP1 expression in a dose-dependent manner. Furthermore, bee venom treatment induced the down-regulation of telomerase reverse transcriptase mRNA and telomeric repeat binding factor expression of A549 cells, however, the levels of telomerase-associated protein-1 and c-myc were not affected. Taken together, these findings suggest that bee venom-induced inhibition of human lung cancer cell growth is associated with the induction of apoptotic cell death via regulation of several major growth regulatory gene products, and bee venom may have therapeutic potential in human lung cancer.

• 한국식품위생안전성학회지
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• 제26권4호
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• pp.398-402
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• 2011

십자화과 채소는 Diindolylmethane (DIM)을 포함한 Isothiocyanates계 화합물을 함유하고 있는데, 이들이 암을 예방하는 효과가 있는 것으로 알려져 있다. 특히 이번 연구에 사용되어진 DIM-C-pPhBr과 DIM-C-pPhF를 기존에 알려진 DIM보다 독성은 최소화되고, 효능은 높은 물질로 보고되어져 있다 하지만, 아직까지 구강편평상피세포암종에서의 세포증식 및 세포사멸에 대한 효능연구는 보고된 바 가 없다. 따라서, 이번 연구에서는 C-DIM 중에 DIM-pPhBr과 DIM-pPhF의 구강편평상피세포암종 세포주인 KB세포에서의 세포증식 및 세포사멸유도효능을 확인함으로써 C-DIM 의 항종양능력을 확인하고자 하였다. 결과를 분석해보면, DIM-C-pPhBr과 DIM-C-pPhF은 구강편평상피세포암종 세포주인 KB의 세포증식을 감소시키고 Western blot분석법, DAPI염색법, 및 Sub-$G_1$축적분석결과에서 알수 있듯이 세포증식을 억제하기 위해 세포사멸을 유도하는 것으로 나타났다. 따라서, DIM-C-pPhBr과 DIM-C-pPhF에 의해 유도되는 세포사멸 및 세포증식억제는 구강암 예방 및 치료를 위한 좋은 전략이 될 수 있을 것으로 사료된다.

• Nutrition Research and Practice
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• 제4권3호
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• pp.177-182
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• 2010

The Chaga mushroom (Inonotus obliquus) has been used in folk medicine to treat cancers. However, limited information exists on the underlying anticancer effects of the major component of I. obliquus in vivo. We hypothesize that the pure compounds ($3{\beta}$-hydroxy-lanosta-8,24-dien-21-al, inotodiol and lanosterol, respectively) separated from I. obliquus would inhibit tumor growth in Balbc/c mice bearing Sarcoma-180 cells (S-180) in vivo and growth of human carcinoma cells in vitro. To test this hypothesis, the growth inhibition of each subfraction isolated from I. obliquus on human carcinoma cell lines (lung carcinoma A-549 cells, stomach adenocarcinoma AGS cells, breast adenocarcinoma MCF-7 cells, and cervical adenocarcinoma HeLa cells) was tested in vitro. Then, after S-180 implantation, the mice were fed a normal chow supplemented with 0, 0.1 or 0.2 mg of subfraction 1, 2 or 3 per mouse per day. All of the subfractions isolated from I. obliquus showed significant cytotoxic activity against the selected cancer cell lines in vitro. Subfraction 1 was more active than subfraction 2 and subfraction 3 against the A549, AGS and MCF-7 cancer cell lines in vitro. In in vivo results, subfraction 1 isolated from I. obliquus at concentrations of 0.1 and 0.2 mg/mouse per day significantly decreased tumor volume by 23.96% and 33.71%, respectively, as compared with the control. Subfractions 2 and 3 also significantly inhibited tumor growth in mice bearing S-180 as compared with the control mouse tumor. Subfraction 1 isolated from I. obliquus showed greater inhibition of tumor growth than subfractions 2 and 3, which agrees well with the in vitro results. The results suggest that I. obliquus and its compounds in these subfractions isolated from I. obliquus could be used as natural anticancer ingredients in the food and/or pharmaceutical industry.

• Asian Pacific Journal of Cancer Prevention
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• 제14권7호
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• pp.4427-4433
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• 2013

Cervical cancer is the second most common cancer in women. HLA class I and II alleles polymorphisms have been shown to be associated with cervical cancer risk, but results have varied among different populations. In this study, the HLA-A, -B, and -DRB1 alleles among 100 southern Chinese women with cervical squamous cell carcinoma (SCC) were compared to 254 controls. Our results showed that $B^*51$:01:02 allele frequency was significantly higher in patients with SCC than in healthy controls ($P=3.17{\times}10^{-5}$, $P_c$=0.005, OR=26.7). Statistical analysis also revealed a significantly decreased frequency of $B^*51$:01:02 ($P=7.01{\times}10^{-4}$, $P_c$=0.03, OR=0.12) in patients with SCC when compared with healthy controls. These results indicate that HLA-$B^*51$:01:02 may confer susceptibility to SCC and HLA-$B^*51$:01:02 may contribute to resistance to the development of SCC in Chinese women. None of the HLA-A-B or HLA-A-B-DRB1 haplotypes were significantly different in cases and controls after multiple testing corrections, indicating the individual allele associations to be independent of the identified haplotypes. These results support the hypothesis that some HLA-B alleles could be involved with susceptibility for developing SCC.

• 동의생리병리학회지
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• 제17권4호
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• pp.1019-1030
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• 2003

Platycodi Radix, the root of Platycodon grandiflorum, commonly known as Doraji, is used as a traditional oriental medicine. Extracts from the roots of P. grandiflorum have been reported to have wide ranging health benefits. In the present study, we investigated the effects of an aqueous extract from the roots of P. grandiflorum (AEPG) on the growth of human lung carcinoma A549 cells. Results obtained are as fellow; AEPG treatment resulted in the inhibition of the cell viability of A549 cells in a concentration-dependent manner. Upon treatment with AEPG, A549 cells developed many of the hallmark features of apoptosis, including condensation of chromatin. Flow cytometry analysis confirmed that AEPG increased populations of apoptotic-sub G1 phase. Western blot and RT-PCR analyses indicated that the expressions of Bcl-2 was down-regulated but Bax was up-regulated in AEPG-treated A549 cells. AEPG-induced apoptotis of A549 cells was associated with rroteolytic cleavage and activation of caspase-3, release of cytochrome c from mitochondria into cytosol and down-regulation of Akt and phospho-Akt proteins in a dose-dependent manner. Induction of apoptosis by AEPG treatment was associated with inhibition and/or degradation of apoptotic target proteins such as poly(ADP-ribose) polymerase, β-catenin and phospholipase C-γ 1. AEPG treatment inhibited the levels of cyclooxygenases protein of A549 cells, which was associated with the inhibition of prostaglandin E2 accumulation in a concentration-dependent fashion. Taken together, these findings suggest that P. grandiflorum has strong potential for development as an agent for prevention against human lung cancer.

• Clinical Endoscopy
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• 제56권1호
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• pp.55-64
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• 2023

Background/Aims: Endoscopic submucosal dissection (ESD) has been established as a treatment modality for superficial esophageal squamous cell carcinoma (ESCC). Long-term follow-up data are lacking in Western countries. The aim of this study was to analyze long-term survival in a Western center. Methods: Patients undergoing ESD for ESCC were included. The analysis was performed retrospectively using a prospectively collected database. Results: R0 resection rate was 96.7% (59/61 lesions in 58 patients). Twenty-seven patients (46.6%) fulfilled the curative resection criteria (M1/M2) (group A), 11 patients (19.0%) had M3 lesions without lymphovascular invasion (LVI) (group B), and 20 patients (34.5%) had lesions with submucosal invasion or LVI (group C). Additional treatment was recommended after non-curative resection. It was not performed in 20/31 patients (64.5%), mainly because of comorbidities (75%). Twenty-nine out of 58 (50.0%) patients died during a mean follow-up of 3.7 years. Death was related to ESCC in 17.2% (5/29) of patients. The disease-specific survival rate after curative resection was 100%. Overall survival rates after 5 years were 61.5%, 63.6% and 28.1% for groups A, B, and C, respectively. The overall survival was significantly worse after non-curative resection (p=0.038). Conclusions: Non-curative resection is frequent after ESD for ESCC in Western patients. The long-term prognosis is limited and mainly determined by comorbidity. Early diagnosis and pre-interventional assessments need to be improved.

• Tuberculosis and Respiratory Diseases
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• 제46권4호
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• pp.523-532
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• 1999

연구배경: 폐암은 조기진단이 어려운 대표적인 종양이다. 최근 정상세포에서 악성조직으로 진행되는 각각의 과정에 대한 연구가 활발해 지면서 폐암의 발병과 진행에 관계하는 여러 유전자와 염색체의 이상들이 발견되고 있다. 이에 근거하여 폐암 중에서도 객담 세포진검사나 기관지내시경 검사 등으로 진단이 용이하고, 조기진단의 의의가 높은 편평상피 폐암을 대상으로 종양세포와 인접 정상 세포에서의 p53 및 c-erbB2의 발현율과 그 의의를 알아보았다. 대상 및 방법: 1995년 5월부터 1996년 11월까지 15개월 동안 편평상피 폐암으로 진단되어 폐절제술을 받은 25명의 환자를 대상으로 하여, 종양부위 및 그 인접 정상세포에서의 p53과 c-erbB2의 발현 여부를 면역조직화학적 검사법을 이용하여 조사하고 폐암의 병리적 병기 및 환자의 생존기간에 따른 발현율의 차이를 후향적으로 조사하였다. 결 과: 25명의 환자 중에서 병리적 병기 I, II가 각각 5명, IIIA가 8명, IIIB가 4명 및 IV가 3명이었다. 종양조직에서의 p53은 12명(48%), erb-B2는 3명(12%)에서 발현되었다. 인접 정상 기관지세포에서는 erb-B2는 3명(12%)에서 발현되었으나 p53은 한 예에서도 발현되지 않았다. 종양세포에서, 병기 II기 이하인 군 10명과 IIIA기 8명 및 IIIB와 IV기의 7명으로 나눠서 비교한 결과 p53이 발현된 경우는 각각 2예, 4예 및 6예로 병기가 진행될수록 발현율은 유의하게 높아졌다(p=0.009 by test of trend). 그러나 종양세포에서 이들의 발현여부에 따른 생존기간은 차이가 없었다. 결 론: p53은 정상 기관지세포에서는 전례에서 발현되지 않았으나 페종양조직에서는 발현율이 48%로 나왔으며, 발현율은 병기가 진행할수록 높아졌다. 따라서 기관지 생검조직에 p53을 이용한 면역조직화학적검사를 병행할 경우 편평상피세포 폐암의 경우 조기진단이나 병기판정에 도움이 될 것으로 추정되나 더 많은 환자를 대상으로 한 연구가 필요할 것으로 생각된다.

• 약학회지
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• 제51권4호
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• pp.239-245
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• 2007

In order to evaluate the genotoxicity of airborne particulate matter extracted with dichloromethane (APE), the rat microsome mediated (S-9) or DNA repair enzyme treated Comet assays were performed using the single cell gel electrophoresis in A549 human lung carcinoma cells. It was found that the cells interacting with APE showed more DNA single-strand breaks relative to untreated cells. The genotoxicity of APE was increased with the treatment of S-9 mixture. Microsome mediated DNA damage was inhibited by CYP1Al inhibitor, quercetin. The APE also showed oxidative DNA damage evaluated by endonuclease III treatment. Oxidative DNA damage of APE was inhibited by antioxidants such as vita- min C and Trolox. We also found that the vegetables or fruits extract may reduce APE-induced genotoxicity by their anti- oxidant activity and CYP1A1 inhibition.

• 한국발생생물학회지:발생과생식
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• 제27권2호
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• pp.77-89
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• 2023

Metformin is the most widely used anti-diabetic drug that helps maintain normal blood glucose levels primarily by suppressing hepatic gluconeogenesis in type II diabetic patients. We previously found that metformin induces apoptotic death in H4IIE rat hepatocellular carcinoma cells. Despite its anti-diabetic roles, the effect of metformin on hepatic de novo lipogenesis (DNL) remains unclear. We investigated the effect of metformin on hepatic DNL and apoptotic cell death in H4IIE cells. Metformin treatment stimulated glucose consumption, lactate production, intracellular fat accumulation, and the expressions of lipogenic proteins. It also stimulated apoptosis but reduced autophagic responses. These metformin-induced changes were clearly reversed by compound C, an inhibitor of AMP-activated protein kinase (AMPK). Interestingly, metformin massively increased the production of reactive oxygen species (ROS), which was completely blocked by compound C. Metformin also stimulated the phosphorylation of p38 mitogen-activated protein kinase (p38MAPK). Finally, inhibition of p38MAPK mimicked the effects of compound C, and suppressed the metformin-induced fat accumulation and apoptosis. Taken together, metformin stimulates dysregulated glucose metabolism, intracellular fat accumulation, and apoptosis. Our findings suggest that metformin induces excessive glucose-induced DNL, oxidative stress by ROS generation, activation of AMPK and p38MAPK, suppression of autophagy, and ultimately apoptosis.