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The Relationship between F-18-FDG Uptake, Hexokinase Activity and Glut-1 Expression in Various Human Cancer Cell Lines (다양한 사람 종양세포주에서 F-18-FDG의 섭취와 Hexokinase 활성 및 Glut-1 발현과의 상관관계)

  • Kim, Bo-Kwang;Chung, June-Key;Lee, Yong-Jin;Choi, Yong-Woon;Jeong, Jae-Min;Lee, Dong-Soo;Lee, Myung-Chul
    • The Korean Journal of Nuclear Medicine
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    • v.34 no.4
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    • pp.294-302
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    • 2000
  • Purpose: To investigate the mechanisms related to F-18-FDG uptake by tumors, F-18-FDG accumulation was compared with glucose transporter-1 (Glut-1) expression and hexokinase activity in various human cancer cell lines. Materials and Methods: Human colon cancer (SNU-C2A, SNU-C4, SNU-C5), hepatocellular carcinoma (SNU-387, SNU-423, SNU-449), lung cancer (NCI-H522, NCI-H358, NCI-H1299), uterine cervical cancer (HeLa, HeLa 229, HeLa S3) and brain tumor (A172, Hs 683) cell lines were used. After 24 hr incubation of $5{\times}10^5$ cells, 37 kBq F-18-FDG was added and the uptake by cells at 10 min was measured using a gamma counter. Hexokinase activity was measured by continuous spectrophotometric rate determination. To measure mitochondrial hexokinase activity, mitochondrial fraction was separated by a high speed centrifuge. Immunohistochemical staining of Glut-1 was performed, and graded as 0, 1, 2, or 3 according to expression. Results: There was difference among F-18-FDG uptake, total and mitochondrial hexokinase activity, and Glut-1 expression with different cancer cell lines. The correlations of F-18-FDG with total hexokinase and mitochondrial hexokinase activity were low (r=0.27 and 0.26, respectively). Glut-1 expression showed a good correlation with F-18-FDG uptake (p=0.81, p=0.0015). Previously, we reported no correlation of F-18-FDG uptake with hexokinase activity in colon cancer cell lines. Thus, when colon cancer cells were excluded, F-18-FDG uptake showed higher correlation with total hexokinase and mitochondrial hexokinase activity (r=0.81, p=0.0027 and r=0.81, p=0.0049, respectively). Conclusion: Both Glut-1 expression and hexokinase activity were contributing factors related to F-18-FDG accumulation in human cancer cell lines. The relative contribution of Glut-1 expression and hexokinase activity, however, was different among different cancer cell types.

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An Assessment of the Utility of Respiratory Synchronized Systems in the PET/CT Examination (PET-CT 검사 시 호흡 동조 시스템들의 유용성 평가)

  • Seong, Yong-Jun;Yoon, Seok-Hwan;Hyun, Jun-Ho;Lee, Hong-jae;Kim, Jin-Eui
    • The Korean Journal of Nuclear Medicine Technology
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    • v.21 no.1
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    • pp.34-38
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    • 2017
  • Purpose During PET/CT examinations, the movements of internal organs caused by respiration are captured in images during multiple breathing cycles, resulting in the increases in tumor size and effects on SUV. Respiratory synchronized systems were used to evaluate tumor sizes and SUV changes. Materials and Methods Biograph mCT 64 was used for the equipment, and RPM and Anzai systems were used for the respiratory synchronized systems. We used point source and micro-phantom for an experimentation. We were performed on 12 patients who had solid tumors discovered at the base of the lung or at the top of the liver from August through September 2016. The PET images of the exhalation-to-breathing state and the CT images of the post-exhalation suspension state were gained to evaluate changes in radioactivity concentration (KBq/mL), SUVmax, cylinder diameter (mm), and tumor diameter (cm) under the conventional Static, RPM, and Anzai methods. Results The result of measuring the radioactivity concentration of the point source was RPM 94% and Anzai 91% against Static, respectively. In the two cylinders of different radioactivity in the micro-phantom, the SUVmax increased to RPM 61% and 78%, and Anzai 58% and 77% against Static, whereas the cylinder diameters decreased by RPM -26% and -28%, and Anzai -28% and -26%, each respectively. Among the patients, the SUVmax increased from a minimum of RPM 8.2% to a maximum of 94.4% against Static, and from a minimum of Anzai 7.6% to a maximum of 68.3%, respectively. As for the tumor diameters, a minimum of RPM -7.6% to a maximum of -28.9% were achieved, while the Anzai fell by a minimum of -9.6% to a maximum of -27.7%, respectively. There was no significant difference discovered in the phantom study between the RPM and Anzai, yet there was a meaningful difference in the patients' tumors (P<0.05). Conclusion The respiratory synchronized systems of RPM and Anzai yielded no significant difference in the phantom study in which the respiration was executed at regular intervals. However, it was discovered that the patients had a meaningful difference for the irregular respiratory cycle and inter-system differences. Still, the respiratory synchronized systems would be useful for the accurate diagnosis and SUV measurement as the tumor decreased in size against the existing Static and the SUV increased.

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Vitamin D Deficiency and Related Factors in Patients at a Hospice (일개 호스피스 병동에서 비타민 D 결핍 현황 및 관련인자)

  • Moon, Kyoung Hwan;Ahn, Hee Kyung;Ahn, Hong Yup;Choi, Sun Young;Hwang, In Cheol;Choi, Youn Seon;Yeom, Chang Hwan
    • Journal of Hospice and Palliative Care
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    • v.17 no.1
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    • pp.27-33
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    • 2014
  • Purpose: Although vitamin D deficiency is more commonly found in cancer patient than in non-cancer patients, there have been little data regarding the prevalence of vitamin D deficiency in cancer patients at the very end of life. We examined vitamin D deficiency in terminally ill cancer patients and related factors. Methods: This study was based on a retrospective chart review of 133 patients in a hospice ward. We collected data regarding age, sex, serum 25-hydroxyvitamin D level, cancer type, physical performance, current medications and various laboratory findings. We investigated factors related to serum vitamin D levels after multivariate adjustment for potential confounders. Serum 25-hydroxyvitamin D<20 ng/mL was considered deficient and <10 ng/mL severely deficient. Results: Ninety-five percent of the patients were serum vitamin D deficient. Severe vitamin D deficiency was more common in male patients, non-lung cancer patients, $H_2$ blocker users and non-anticonvulsant users. Elevated levels of serum alanine aminotransferase (ALT) were also associated with low serum vitamin D levels. Multiple regression analysis showed that severe vitamin D deficiency was associated with male gender (aOR 3.82, 95% CI: 1.50~9.72, P=0.005), $H_2$ blocker users (aOR 3.94, 95% CI: 1.61~9.65, P=0.003) and elevated serum ALT levels (aOR 4.52, 95% CI: 1.35~15.19, P=0.015). Conclusion: Vitamin D deficiency was highly prevalent among terminally ill cancer patients. Severe vitamin D deficiency was more common in male patients, $H_2$ blocker users, and patients with elevated ALT levels.

Antimutagenic and Cytotoxicity Effects of Agaricus blazei Murill Extracts (아가리쿠스버섯(Agaricus blazei Murill) 추출물의 항돌연변이원성 및 세포독성 효과)

  • Ji, Jeong-Hwan;Kim, Mi-Nam;Choi, Kun-Pyo;Chung, Cha-Kwon;Ham, Seung-Shi
    • Korean Journal of Food Science and Technology
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    • v.32 no.6
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    • pp.1371-1378
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    • 2000
  • This study was performed to determine the antimutagenic and cytotoxic effect of Agaricus blazei Murill methanol extract on Salmonella typhimurium TA98, TA100 and human cancer cell lines using Ames test and cytotoxicity assay, respectively. In Ames test, methanol extract from A. blazei Murill did not exhibit any mutagenicity and most of the samples showed high antimutagenic effects against mutation induced by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG), 4-nitroquinoline-1-oxide(4NQO), 3-amino-1,4-dimethyl-5H-pyrido [4,3-b] indol(Trp-P-1) and $benzo({\alpha})pyrene(B({\alpha})P)$. The methanol extracts of A. blazei Murill$(200\;{\mu}g/plate)$ showed approximately 92.4%, 81.9% and 83.4% inhibitory effect on the mutagenesis induced by 4NQO, Trp-P-1 and $B({\alpha})P$ against TA98 strain, whereas 87.3%, 94.7%. 92.3% and 89.9% inhibitions were observed on the mutagenesis induced by MNNG, 4NQO, Trp-P-1 and $B({\alpha})P$ against TA100 strain. The solvent fractions of methanol extracts from A. blazei Murill except water fraction showed high antimutagenic effects of $70{\sim}90%$ against mutation induced by MNNG, 4NQO. Trp-P-1 and $B({\alpha})P$. In anticancer effects of A. blazei Murill extract and fraction against cancer cell lines including human breast adenocarcinoma(MCF7), human lung carcinoma(A549), human fibrosarcoma(HT1080), human hepatocellular carcinoma(Hep3B), human epitheloid carcinoma(HeLa), human gastric carcinoma(KATO III) and human chronic myelogenous leukemia(K562) were investigated. The treatment of 1 mg/mL A. blazei Murill extracts had the highest cytotoxicity with 91.9% against HeLa, followed by KATO III(88.7%), A549(86.5%) and Hpe3B(84.3%). Whereas 1 mg/mL treatment of A. blazei Murill extracts had only $10{\sim}40%$ cytotoxicity on human normal liver cell (WRL68).

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Reduced Ovarian Cancer Incidence in Women Exposed to Low Dose Ionizing Background Radiation or Radiation to the Ovaries after Treatment for Breast Cancer or Rectosigmoid Cancer

  • Lehrer, Steven;Green, Sheryl;Rosenzweig, Kenneth E
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.6
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    • pp.2979-2982
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    • 2016
  • Background: High dose ionizing radiation can induce ovarian cancer, but the effect of low dose radiation on the development of ovarian cancer has not been extensively studied. We evaluated the effect of low dose radiation and total background radiation, and the radiation delivered to the ovaries during the treatment of rectosigmoid cancer and breast cancer on ovarian cancer incidence. Materials and Methods: Background radiation measurements are from Assessment of Variations in Radiation Exposure in the United States, 2011. Ovarian cancer incidence data are from the Centers for Disease Control and Prevention. Standardized incidence ratios (SIR) of ovarian cancer following breast cancer and rectosigmoid cancer are from Surveillance, Epidemiology, and End Results (SEER) data. Obesity data by US state are from the Centers for Disease Control and Prevention. Mean ages of US state populations are from the United States Census Bureau. Results: We calculated standardized incidence ratios (SIR) from Surveillance, Epidemiology, and End Results (SEER) data, which reveal that in 194,042 cases of breast cancer treated with beam radiation, there were 796 cases of ovarian cancer by 120+ months of treatment (0.41%); in 283, 875 cases of breast cancer not treated with radiation, there were 1,531 cases of ovarian cancer by 120+ months (0.54%). The difference in ovarian cancer incidence in the two groups was significant (p < 0.001, two tailed Fisher exact test). The small dose of scattered ovarian radiation (about 3.09 cGy) from beam radiation to the breast appears to have reduced the risk of ovarian cancer by 24%. In 13,099 cases of rectal or rectosigmoid junction cancer treated with beam radiation in the SEER data, there were 20 cases of ovarian cancer by 120+ months of treatment (0.15%). In 33,305 cases of rectal or rectosigmoid junction cancer not treated with radiation, there were 91 cases of ovarian cancer by 120+ months (0.27%). The difference in ovarian cancer incidence in the two groups was significant (p = 0.017, two tailed Fisher exact test). In other words, the beam radiation to rectum and rectosigmoid that also reached the ovaries reduced the risk of ovarian cancer by 44%. In addition, there was a significant inverse relationship between ovarian cancer in white women and radon background radiation (r = - 0.465. p = 0.002) and total background radiation (r = -0.456, p = 0.002). Because increasing age and obesity are risk factors for ovarian cancer, multivariate linear regression was performed. The inverse relationship between ovarian cancer incidence and radon background was significant (${\beta}=-0.463$, p = 0.002) but unrelated to age (${\beta}=-0.080$, p = 0.570) or obesity (${\beta}=-0.180$, p = 0.208). Conclusions: The reduction of ovarian cancer risk following low dose radiation may be the result of radiation hormesis. Hormesis is a favorable biological response to low toxin exposure. A pollutant or toxin demonstrating hormesis has the opposite effect in small doses as in large doses. In the case of radiation, large doses are carcinogenic. However, lower overall cancer rates are found in U.S. states with high impact radiation. Moreover, there is reduced lung cancer incidence in high radiation background US states where nuclear weapons testing was done. Women at increased risk of ovarian cancer have two choices. They may be closely followed (surveillance) or undergo immediate prophylactic bilateral salpingo-oophorectomy. However, the efficacy of surveillance is questionable. Bilateral salpingo-oophorectomy is considered preferable, although it carries the risk of surgical complications. The data analysis above suggests that low-dose pelvic irradiation might be a good third choice to reduce ovarian cancer risk. Further studies would be worthwhile to establish the lowest optimum radiation dose.

Cytotoxicity and Antigenotoxic Effects of Cordyceps militaris Extracts (번데기동충하조(Cordyceps militaris) 추출물의 세포독성 및 유전독성 억제효과)

  • 김미남;최승필;이득식;함승시
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.30 no.5
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    • pp.921-927
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    • 2001
  • This study was performed to investigated the effects on the cytotoxicity and antigenotoxicity of Cordyceps militaris extracts on the human cancer cell lines. The ethanol extract and five fractions which were hexane, chloroform, ethylacetate, butanol and aqueous were screened for crytotoxicity on human lung carcinoma(A549). human breast adenocarcinoma (MCF-7) human epitheloid carcinoma(HeLa), human fibrosarcoma(HT1080) human hepatocellular carcinoma(Hep3B), human gastric carcinoma(KATOIII) and chronic myelogenous leukemia(K562) cell by SRB and MTT assays. The results showed that growth inhibition rates of the human cancer cell in the presence of Cordyceps militaris were inhibited with increasing concentration of the extract. The ethanol extract from Cordyceps militaris had strong inhibitory effects in1 mg/mL treatment by SRB assay , showing 89.4%, 85.7%, 72.9% and 65.5% inhibition in HT1080, HeLa, Hep3B and A549, respectively. The treatment of 1 mg/mL hexane fraction by SRB assay had the strongest cytotoxicity with 97.0% on HT1080 followed by MCF-7(92.9%) and HeLA(90.3%). The inhibition ration on KATOIII by MTT assay was much higher in the butanol (83.7%) and aqueous (80.4%) than in the ethanol extract (61.5%) And also, K562 showed similar tendency with KATOIII. The effects of Cordyceps militaris extracts on the frequencies of micronucleated polychromatic erythrocytes (MNPCEs) induced by N-methyl-N-nitro-N-nitrosoguanidime(MNNG) were investigated in the bone-marrow cells of ICR male mice. The amount of 10, 20, 40 and 80 mg/kg of each extract were administered to animals immediately after injection of MNNG, and the exposure time was 36 hours. Significant reductions(p<0.05) with 39.7%, 52.7%, 71.4% and 83.9% were observed in the frequencies of MNPCE when 10, 20, 40 and 80 mg/kg of the hexane fraction of Coryceps militarus extracts were given to the mice.

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Biological Activities and Physiochemical Properties of Gangwon-do Endemic Makjang Products (강원도 시판 막장제품의 이화학적 품질특성 및 생리활성 조사)

  • Kim, Byoung-Mok;Jung, Jee-Hee;Lim, Ji-Hoon;Jung, Min-Jeong;Jeong, Jae-Whung;Choi, Yong-Suck;Sim, Jea-Man;Jeong, In-Hak;Kim, Young-Myoung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.6
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    • pp.862-873
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    • 2015
  • In this study, we investigated the physiochemical properties and biological activities of Gangwon-do endemic Makjang (MJ) products (12 types). The pH levels of all samples were in the range of 4.43 to 5.69, and MJ5 showed the highest pH (5.69). The salinities of all samples ranged from 11.1% to 16.9%. Hunter color values for L (lightness), a (redness), and b (yellowness) ranged from 26.2 to 36.9, 3.9 to 11.5, and 6.5 to 16.6, respectively. The amino nitrogen content of MJ2 was highest, whereas the total content of free amino acids of MJ11 (4,657.7 mg%) was highest. Total fatty acid contents of all samples ranged from 1,598.6 mg% to 2,874.4 mg%, with MJ10 showing the highest fatty acid content. The content of total polyphenolic compounds ranged from 401.48 to $746.67{\mu}g$ tannic acid equivalent/mL, with MJ11 showing the highest content. The 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiozoline-6-sulfonic acid) radical scavenging effects of MJ11, MJ8, and MJ4 were 51.30% and 82.5%, 41.29% and 67.0%, and 49.88% and 87.7%, respectively. MJ12 showed the strongest growth inhibitory effect on lung cancer A549 cells, whereas MJ5 showed the strongest growth inhibitory effect on AGS gastric cancer cell and MCF-7 breast cancer cell. MJ7 showed greater lipid accumulation inhibitory activity in HepG2 cells than the others. ACE inhibitory activity of MJ11 was the highest among the samples.

Activation and Abnormalities of Cell Cycle Regulating Factor in Head and Neck Squamous Cell Carcinoma Cell Lines: Abnormal Expression of CDKN2 Gene in Laryngeal Squamous Cell Carcinoma (두경부 편평상피세포암 세포주에서 세포주기조절인자의 활성 및 이상 : 후두편평상피세포암에서 종양억제유전자 CDKN2 유전자의 발현이상)

  • Song, Si-Youn;Han, Tae-Hee;Bai, Chang-Hoon;Kim, Yong-Dae;Song, Kei-Won
    • Journal of Yeungnam Medical Science
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    • v.22 no.2
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    • pp.166-182
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    • 2005
  • Background: Cyclin-dependent kinase (CDK) inhibitors are family of molecules that regulate the cell cycle. The CDKN2, a CDK4 inhibitor, also called p16, has been implicated in human tumorigenesis. The CDKN2 inhibits the cyclin/CDK complexes which regulate the transition from G1 to S phase of cell cycle. There is a previous report that homozygous deletion of CDKN2 region on chromosome 9p21 was detected frequently in astrocytoma, glioma and osteosarcoma, less frequently in lung cancer, leukemia and ovarian cancer, but not detected in colon cancer and neuroblastoma. However, little is known about the relationship between CDKN2 and laryngeal cancer. Therefore this study was initiated to investigate the role of CDKN2 in human laryngeal squamous cell carcinoma development.1) Materials and methods: We used 5 human laryngeal carcinoma cell lines whether they have deletions or losses of CDKN2 gene expression by DNA-PCR or RT-PCR, respectively. We examined 8 fresh frozen human laryngeal cancer tissues to detect the loss of heterozygosity (LOH) of CDKN2. PCR was performed by using microsatellite markers of short arm of human chromosome 9 (D9S126, D9S144, D9S156, D9S161, D9S162, D9S166, D9S171, D9S200 and D9SIFNA). For informative cases, allelic loss was scored if the signal of one allele was significantly decreased in tumor DNA when compared to the same allele in normal DNA. Results: The CDKN2 DNA deletion was observed in 3 cell lines. The CDKN2 mRNA expression was observed in only one cell line, which was very weak. LOH was detected in 7 cases (87.5%). Conclusion: These results suggest that CDKN2 plays a role in the carcinogenesis of human laryngeal squamous cell carcinoma.

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Antioxidative, Antimutagenic and Cytotoxic Effects of Prunus armeniaca Extracts (살구 추출물의 항산화성, 항돌연변이성 및 세포독성 효과)

  • Yoo, Su-Jung;Kim, Soo-Hyun;Jun, Mi-Sun;Oh, Hyun-Taek;Choi, Hyun-Jin;Ham, Seung-Si
    • Food Science and Preservation
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    • v.14 no.2
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    • pp.220-225
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    • 2007
  • This study was performed to measure the antioxidative, antimutagenic, and cytotoxic properties of Prunus armeniaca using the DPPH (1, 1-diphenyl-2-picrylhydrazyl) free radical donating method, the Ames test, and cytotoxicity measurements, respectively. Electron-donating abilities were 48.3, 43.9, 14.8 and 12.9 per g dry matter of P. armeniaca seed (PAS), P. armeniaca flesh(PAF), butylated hydroxytoluene, and ${\alpha}-tocopherol$, respectively. The direct antimutagenic effects of an ethanol extract of P. armeniaca were examined in Ames tests using Salmonella typhimurium TA98 and TA100 as reporter organisms. In the Ames test, the ethanol extract of P. armenicaca alone did not exhibit any mutagenicity but the extract did show substantial inhibitory effects against mutations induced by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) and 4-nitroquinoline-1-oxide(4NQO). The ethanol extract of PAS(200g dry matter/plate) inhibited strain TA98 mutagenesis induced by 4NQO by ca. 37.9%, and mutation inhibition values of 42.1% and 69.4%, respectively, were observed when 4NQO and MNNG acted on the TA100 strain. The cytotoxic effects of ethanol extracts of P. armeniaca against cell lines of human lung carcinoma(A549), human breast adenocarcinoma(MCF-7), human hepatocellular carcinoma(Hep3B), human cervical adenocarcinoma(HeLa), and human gastric carcinoma(AGS) rose with increases in extract concentration. An ethanol extract(4mg/mL dry matter) of PAF showed strong cytotoxicities of 88.2%, 58%, 72.8%, 89.4%, and 91.9% against A549, AGS, MCF-7, HeLa, and Hep3B cells, respectively. In contrast, the same extract showed only 13 37% cytotoxicity for a nomal human kiney cell line(293). It is suggested that P. armeniaca possesses useful antioxidative, antimutagenic, and anticancer properties.

Cytotoxicity of Particulate Matter in Various Human Cells Lines (미세먼지가 다양한 사람 세포주에 미치는 세포 독성)

  • Lee, Ji-Hyeon;Lee, Joo-Yeong;Kim, Mi-Jeong;Kim, Hyeon-Ji;Lee, Sung-Ho;Jeon, Byeong-Gyun
    • Journal of Life Science
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    • v.29 no.6
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    • pp.724-734
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    • 2019
  • The present study investigated the cytotoxicity of particulate matter (PM) derived from car air filter (outdoor PM) and home cleaner filter (indoor PM) in the various human cell lines. Each outdoor and indoor PM were harvested by ethanol extraction method, subsequently sieved with 10 um filter paper, sterilized with autoclave and added to culture media. The half maximal inhibitory concentration ($IC_{50}$) values was significantly (p<0.05) lower in the outdoor PM, compared with indoor PM, and the significantly (p<0.05) higher $IC_{50}$ values were observed in the cancer cell lines (A-549 lung adenocarcinoma and AGS stomach adenocarcinoma), than those of normal MRC-5 fibroblasts and dental papilla tissue derived-mesenchymal stem cells (DSC). After being exposed to $100{\mu}g/ml$ outdoor PM for 7 days, the population doubling time (PDT) was significantly (p<0.05) increased in especially MRC-5 and DSC cell lines, compared with untreated cell lines. Further, the expression of senescence-associated ${\beta}$-galactosidase activity was up-regulated in all the cells exposed to outdoor PM than those of untreated control. Besides, the expression level of inflammation-associated genes, such as cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) was found to be significantly (p<0.05) increased in the outdoor PM-treated cell lines than those of untreated cell lines. Our results showed that PM induces the cytotoxicity via arrest of cell growth, cell damage and inflammation response.