• 제목/요약/키워드: Cancer stem cells

검색결과 364건 처리시간 0.025초

Immunomodulatory activity of phytoprotein isol Acanthopanax senticosus : Regulation of CTL responses and activation of macrop

  • Lee Seok Won;Lee Soo Jin;Park Jeon Ran;Kim Ha na;Ahn Kyoo Seok;Kim Jung-Hyo;Baek Nam-in;Kim Sung Hoon
    • 동의생리병리학회지
    • /
    • 제18권1호
    • /
    • pp.230-235
    • /
    • 2004
  • We previously reported that the phytoprotein extracted from Acanthopanax senticosus (PA) had anti-carcinogenic anti-metastatic activity via increase of inhibition of gap junctional intercellular communication. In the present study investigated the immunomodulatory mechanism of phytoprotein isolated from the stem bark of Acanthopanax sentic (PA). PA was found to significantly stimulate macrophages producing TNF-α and IL-1β in vitro. It also showed tumori activity indicating that PA had the ability to stimulate macrophage directly. Moreover, PA induced the CDB/sup +/ CTL cy responses to recognize antigen on the B16-BL6 melanoma cells. Treatment of PA with B16-BL6 melanoma cells increased the proliferation of splenocytes compared with untreated control. These results demonstrate that PA immunomodulatory activity suggesting a useful anti-tumor agent applicable to treatment and prevention of cancer.

Anti-Cancer Effect of Ginsenoside F2 against Glioblastoma Multiforme in Xenograft Model in SD Rats

  • Shin, Ji-Yon;Lee, Jung-Min;Shin, Heon-Sub;Park, Sang-Yong;Yang, Jung-Eun;KimCho, So-Mi;Yi, Tae-Hoo
    • Journal of Ginseng Research
    • /
    • 제36권1호
    • /
    • pp.86-92
    • /
    • 2012
  • The glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. Despite combination treatments of radiation and chemotherapy, the survival periods are very short. Therefore, this study was conducted to assess the potential of ginsenoside $F_2$ (F2) to treat GBM. In in vitro experiments with glioblastoma cells U373MG, F2 showed the cytotoxic effect with $IC_{50}$ of 50 ${\mu}g/mL$ through apoptosis, confirmed by DNA condensation and fragmentation. The cell population of cell cycle sub-G1 as indicative of apoptosis was also increased. In xenograft model in SD rats, F2 at dosage of 35 mg/kg weight was intravenously injected every two days. This reduced the tumor growth in magnetic resonance imaging images. The immunohistochemistry revealed that the anticancer activity might be mediated through inhibition of proliferation judged by Ki67 and apoptosis induced by activation of caspase-3 and -8. And the lowered expression of CD31 showed the reduction in blood vessel densities. The expression of matrix metalloproteinase-9 for invasion of cancer was also inhibited. The cell populations with cancer stem cell markers of CD133 and nestin were reduced. The results of this study suggested that F2 could be a new potential chemotherapeutic drug for GBM treatment by inhibiting the growth and invasion of cancer.

발효옻 추출물의 헬리코박터파이로리 생장억제 및 항염증 활성 (Anti-inflammatory activities of fermented Rhus verniciflua stem bark extract and its growth inhibitory effect on Helicobacter pylori)

  • 최은영;석기태;최한석;김명곤;권용수;김명조
    • 한국식품과학회지
    • /
    • 제48권5호
    • /
    • pp.502-507
    • /
    • 2016
  • 본 연구는 장수버섯(Fomitella fraxinea)을 이용하여 발효처리 한무독화 옻나무 추출물의 위장기능 개선능을 확인하고자 발효옻추출물을 이용하여 H. pylori 생장억제활성, 위암세포 생장억제활성과 항염증 활성을 평가하였다. H. pylori를 접종한 배지에 발효옻 추출물을 농도별로 첨가하였을 때 2.0 mg의 농도에서 4.0 mm의 생장억제환을 확인하였으며, 발효옻 추출물을 배지에 1.0-5.0 mg 농도로 혼합한 후 H. pylori을 접종한 경우에도 생장억제능이 확인되었다. 이를 바탕으로 세포 수준에서 H. pylori에 의해 유발된다고 알려진 위암과 위염 개선능을 평가하고자 세포독성을 나타내지 않은 0.1-1.0 mg/mL의 농도범위로 AGS 위암세포 생장억제활성 및 NO 생성 저해율을 확인하였다. 실험결과 0.25 mg/mL 이상의 농도에서 20% 이상의 위암세포 생장억제활성을 확인하였으며, LPS로 염증을 유도한 RAW 264.7 세포에서 추출물 0.25 mg/mL처리시 90%의 높은 NO 생성 저해율을 확인하였다. 염증유발인자인 iNOS와 COX-2의 발현 억제율은 0.50 mg/mL 농도에서 각각 50, 10%의 억제율을 보여 NO 생성저해율은 iNOS에 의한 영향인 것으로 사료된다. 상기 결과로 발효옻 추출물은 H. pylori 생장억제능 및 높은 NO 생성저해 활성이 확인됨으로서 간접적인 위암발생 억제제 및 항염증제로서의 이용가능성을 확인하였다. 따라서 발효옻 추출물을 이용한 위장개선 식의약 소재로서의 개발 가능성이 매우 높은 것으로 생각되며 이를 위해 추가적인 연구가 진행되어야 할 것으로 사료된다.

Anti-gastritic Effects of Magnolol and Honokiol from the Stem Bark of Magnolia obovata

  • Cho, So-Yean;Lee, Je-Hyuk;Bae, Ki-Hwan;Kim, Yeong-Shik;Jeong, Choon-Sik
    • Biomolecules & Therapeutics
    • /
    • 제16권3호
    • /
    • pp.270-276
    • /
    • 2008
  • In this study we investigated the effects of Magnolia Bark (MB) extract and its constituents, such as honokiol and magnolol, on gastritis in rats and the growth of human gastric cancer cells. The MB extract, honokiol, and magnolol showed the acid-neutralizing capacities, the antioxidant activities, and the inhibitory effect on the growth of Helicobacter pylori (H. pylori.) at the dose of $50\;{\mu}g/ml$ and over, which is equivalent to that of ampicillin ($100\;{\mu}g/ml$). Honokiol and magnolol had no significant cytotoxicity to human gastric caner cells (AGS and SNU638). However, the MB extract had cytotoxic activity against AGS gastric cancer cell. The MB extract, honokiol, and magnolol significantly inhibited HCI-ethanol-induced gastric lesions without clear change of mucus content. In pylorus ligated rats, honokiol significantly decreased the volume of gastric secretion and gastric acid output, and increased the pH. Magnolol increased the mucus content to almost the same as the control group at oral doses of 50 mg/kg. Therefore, we could guess that antigastritic action of honokiol and magnolol may be associated with the antioxidant activities, acid-neutralizing capacities, inhibition of secretion in gastric acid, and anti-H. pylori action. From these results, we could suggest that MB extract and its constituents, such as honokiol and magnolol, may be useful for the treatment and/or protection of gastritis.

산겨릅나무 추출물의 이화학적 특성과 암세포 성장 억제 효과 (The Physical and Chemical Properties and Cytotoxic Effects of Acer tegmentosum Maxim. Extracts)

  • 신인철;사재훈;심태흠;이진하
    • Applied Biological Chemistry
    • /
    • 제49권4호
    • /
    • pp.322-327
    • /
    • 2006
  • 우리나라 중부 이북 해발 500m 이상의 고산지대에서 주로 자생하는 산겨릅나무(Acer tegmentosum Maxim.)를 대상으로 식품학적인 성분 분석과 산겨릅나무 줄기의 EtOH추출물의 분획물을 제조하여 DPPH 유리기 대한 소거 기능, 그리고 사람 유래의 암세포들(위암세포(AGS), 간암세포(HepG2), 폐암세포(A549)와 유방암세포(MCF-7))에 대한 항암 효과를 조사하여 다음과 같은 결과를 얻었다. 1) 산겨릅나무 줄기 의 식품성분 함량은 탄수화물이 58.4%, 수분 27.5%, 조단백질 8.7%, 조지방 3.8%, 조회분 1.6%의 순으로 나타났고 무기질의 주요 무기성분은 K과 Ca이 302.4mg%와 116.0mg%로 가장 많이 함유되어 있고 Mg, Na, Mn, Fe, Zn, P, Cu의 함량이 각각 57.8, 24.8, 9.5, 4.4, 1.6, 0.8, 0.2 mg% 순으로 나타났다. 2) DPPH를 이용한 항산화 효능을 보기위하여 산겨릅나무 줄기의 수피부 및 줄기를 80% EtOH로 추출하고, 그 추출물들을 다시 n-hexane, chloroform, EtOAc, n-BuOH 및 aqueous층으로 분리하였다. 분획물들을 대상으로 DPPH 유리기의 소거능을 검증한 결과 전반적으로 줄기 보다는 수피부에서 높은 소거 효과를 나타냈으며 용매별로는 EtOAc>n-BuOH>aqueous>chloroform>n-hexane 순으로 활성을 보였다. 특히, EtOAc fr.($SC_{50}:2.8{\mu}g/ml$과 n-BuOH fr.($SC_{50}:3.2{\mu}g/ml$은 천연항산화제로 쓰이는 ascorbic acid($SC_{50}:4.5{\mu}g/ml$$\alpha$-tocopherol($SC_{50}:4.0{\mu}g/ml$ 및 합성 항산화제인 BHT($SC_{50}:6.5{\mu}g/ml$보다도 높은 소거능을 보였다. 3) 유리기의 소거 기능과 분획물들의 성분과의 상호 관계를 조사하기 위하여 각 분획물들의 흡광도를 조사한 결과, 페놀성계 화합물계의 특성을 보이는 280nm부근에서 강한 흡광도를 나타내어 DPPH에 의한 높은 항산화 효능이 페놀성계 성분과 관계가 깊은 것으로 사료되었다. 4) 산겨릅나무 줄기의 80% EtOH 추출물의 암 세포주들에 대한 성장 저해와 정상세포에 대한 세포 독성을 알아보기 위하여 인체기원 세포주인 간암세포(HepG2), 위암세포(AGS),폐암세포(A549), 유방암세포(MCF-7)와 정상 간세포(Chang)를 대상으로 추출농도 0.125, 0.25, 0.5, 1(mg/ml) 등 4단계로 나누어 실험하였으며 다음과 같은 결론을 얻었다. 위암세포의 경우 0.125mg/ml의 저농도에서 50% 이상, 0.5mg/ml에서는 90% 이상의 암세포 생육 억제효과를 보여주었다. 간암세포를 포함한 나머지 폐암세포와 유방암세포의 경우 모두 0.5mg/ml에서 50%이상의 세포 성장 억제 효과를 나타내었다.

Highly Expressed Integrin-α8 Induces Epithelial to Mesenchymal Transition-Like Features in Multiple Myeloma with Early Relapse

  • Ryu, Jiyeon;Koh, Youngil;Park, Hyejoo;Kim, Dae Yoon;Kim, Dong Chan;Byun, Ja Min;Lee, Hyun Jung;Yoon, Sung-Soo
    • Molecules and Cells
    • /
    • 제39권12호
    • /
    • pp.898-908
    • /
    • 2016
  • Despite recent groundbreaking advances in multiple myeloma (MM) treatment, most MM patients ultimately experience relapse, and the relapse biology is not entirely understood. To define altered gene expression in MM relapse, gene expression profiles were examined and compared among 16 MM patients grouped by 12 months progression-free survival (PFS) after autologous stem cell transplantation. To maximize the difference between prognostic groups, patients at each end of the PFS spectrum (the four with the shortest PFS and four with the longest PFS) were chosen for additional analyses. We discovered that integrin-${\alpha}8$ (ITGA8) is highly expressed in MM patients with early relapse. The integrin family is well known to be involved in MM progression; however, the role of integrin-${\alpha}8$ is largely unknown. We functionally overexpressed integrin-${\alpha}8$ in MM cell lines, and surprisingly, stemness features including $HIF1{\alpha}$, VEGF, OCT4, and Nanog, as well as epithelial mesenchymal transition (EMT)-related phenotypes, including N-cadherin, Slug, Snail and CXCR4, were induced. These, consequently, enhanced migration and invasion abilities, which are crucial to MM pathogenesis. Moreover, the gain of integrin-${\alpha}8$ expression mediated drug resistance against melphalan and bortezomib, which are the main therapeutic agents in MM. The cBioPortal genomic database revealed that ITGA8 have significant tendency to co-occur with PDGFRA and PDGFRB and their mRNA expression were up-regulated in ITGA8 overexpressed MM cells. In summary, integrin-${\alpha}8$, which was up-regulated in MM of early relapse, mediates EMT-like phenotype, enhancing migration and invasion; therefore, it could serve as a potential marker of MM relapse and be a new therapeutic target.

사람의 다양한 조직에서 기원하는 암세포 및 정상세포에 대한 penta-O-galloyl-β-D-glucose의 세포독성 효과 (Differential Cytotoxicity of Penta-O-galloyl-β-D-glucose in Human Cancer and Normal Cell Lines of Various Origins)

  • 이현정;김민경;이송영;송민혁;김윤동;하정숙;정계준;노규진;전병균
    • 생명과학회지
    • /
    • 제26권11호
    • /
    • pp.1320-1329
    • /
    • 2016
  • 본 연구는 다당체의 한 종류인 penta-O-galloyl-${\beta}$-D-glucose (PGG)가 사람의 여러 조직에서 기원하는 여러 암세포주(A-549, MDA-MB-231, U87-MG, MCF-7 및 PANC-1), 정상 MRC-5 태아 섬유아세포 그리고 사랑니에서 유래한 간엽줄기세포(DPSCs)에 미치는 세포독성 효과를 조사하였다. $IC_{50}$값은 다른 세포주에 비해 높은 증식률을 나타내는 A-549 및 MDA-MB-231 암세포주에서 유의적으로 낮게 관찰되었다. 10 uM의 PGG가 포함된 배양액에서 세포를 7일 동안 배양한 결과, 세포배가시간은 모든 세포주에서 유의적으로 늘어났고, 세포배가시간과 $IC_{50}$값의 관계를 조사한 결과, 세포배가시간이 늘어남에 따라 $IC_{50}$값은 비례적으로 증가됨을 증명하였다. 또한, 10 uM의 PGG로 처리된 세포주들은 노화와 관련된 ${\beta}-galactosidase$의 활성도가 높게 관찰되었다. 특히, telomerase 활성도는 A-549 및 MDA-MB-231 암세포주에서 다른 세포주에 비하여 현저히 감소하는 것을 관찰하였다. 이러한 결과를 바탕으로 PGG는 높은 증식률을 보이는 암세포주에서 높은 세포독성효과를 나타내어 잠재적인 항암물질임을 증명하였다.

Current and Future Perspectives of Lung Organoid and Lung-on-chip in Biomedical and Pharmaceutical Applications

  • 이준형;박지민;김상훈;한에스더;맹성호;한지유
    • 생명과학회지
    • /
    • 제34권5호
    • /
    • pp.339-355
    • /
    • 2024
  • 폐는 생리학적 기능과 해부 조직학적 구조 측면을 통합적으로 고려하여 분석해야만 하는 매우 복잡한 조직이기 때문에 폐질환의 병리학적 연구와 흡입독성 평가에 현재까지 주로 동물모델을 사용하고 있다. 그러나 실험동물 윤리와 동물복지를 이유로 점차적으로 실험동물 수를 줄이자는 전세계적인 움직임에 맞춰 생체 외 동물실험 대체법들이 집중적으로 개발되고 있다. 특히 경제협력개발기구(OECD)와 미국 환경보호청(USEPA)은 2030년대 이후, 동물실험을 금지하기로 잠정적으로 합의함에 따라 의생명공학과 제약 분야에서 생체 외 흡입 독성 및 폐질환 모델들을 확립하고 개발된 모델을 이용한 평가 법들의 표준화 연구가 활발하다. 그 모델 중에 예를 들어, 생체칩(organ-on-a-chip, OoC) 및 오가노이드(organoid) 모델은 3차원 바이오 프린터, 미세 유체 시스템, 인공지능(artificial intelligent) 기술들과 접목되어 연구되고 있다. 이러한 생체 장기를 모방한 복합 장기 생체 외 모델링 시스템은 개체 차이를 가지는 생체 내 동물 실험에 비해 복잡한 생물학적 환경을 보다 정확하게 모방할 수 있을 것으로 기대되고 있으나 생체 모방성, 재현성, 민감성, 기반 데이터베이스의 부족 등 아직은 여러 한계점도 가지고 있다. 따라서 본 리뷰 논문에서는 만능성 줄기 세포 또는 암세포를 이용한 폐포, 폐 공기액 인터페이스(air-liquid interface, ALI) 시스템, 트랜스웰 멤브레인(transwell membrane)을 포함하여 폐 OoC 및 오가노이드의 최근 생체 외 폐 시스템 연구결과들과 AI와 접목된 인실리코(in silico) 폐 모델링에 대한 결과들의 현황을 살펴보고자 한다.

Secretion and Expression of Matrix Metalloproteinase-2 and 9 from Bone Marrow Mononuclear Cells in Myelodysplastic Syndrome and Acute Myeloid Leukemia

  • Chaudhary, Ajay K;Chaudhary, Shruti;Ghosh, Kanjaksha;Shanmukaiah, Chandrakala;Nadkarni, Anita H
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제17권3호
    • /
    • pp.1519-1529
    • /
    • 2016
  • Background: Matrix metalloproteinase -2 (gelatinase-A, Mr 72,000 type IV collagenase, MMP-2) and -9 (gelatinase-B, Mr 92,000 type IV collagenase, MMP-9) are key molecules that play roles in tumor growth, invasion, tissue remodeling, metastasis and stem-cell regulation by digesting extracellular matrix barriers. MMP-2 and -9 are well known to impact on solid cancer susceptibility, whereas, in hematological malignancies, a paucity of data is available to resolve the function of these regulatory molecules in bone marrow mononuclear cells (BM-MNCs) and stromal cells of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Objectives: The present study aimed to investigate mRNA expression and gelatinase A and B secretion from BM-MNCs in vitro and genotypic associations of MMP-2 (-1306 C/T; rs243865), MMP-9 (-1562 C/T; rs3918242), tissue inhibitor of metalloproteinase -1 (TIMP-1) (372T/C; rs4898, Exon 5) and TIMP-2 (-418G/C; rs8179090) in MDS and AML. Results: The study covered cases of confirmed MDS (n=50), AML (n=32) and healthy controls (n=110). MMP-9 mRNA expression revealed 2 fold increased expression in MDS-RAEB II and 2.5 fold in AML M-4 (60-70% blasts). Secretion of gelatinase-B also revealed the MMP-9 mRNA expression and ELISA data also supported these data. We noted that those patients having more blast crises presented with more secretion of MMP-9 and its mRNA expression. In contrast MMP-9 (-1562 C/T) showed significant polymorphic associations in MDS (p<0.02) and AML (p<0.02). MMP-9 mRNA expression of C/T and T/T genotypes were 1.5 and 2.5 fold increased in MDS and AML respectively. In AML, MMP-2 C/T and T/T genotypes showed 2.0 fold mRNA expression. Only MMP-9 (-1306 C/T) showed significant 4 fold (p<0.001) increased risk with chemical and x-ray exposed MDS, while tobacco and cigarette smokers have 3 fold (p<0.04) risk in AML. Conclusions: In view of our results, MMP-9 revealed synergistic secretion and expression in blast crises of MDS and AML with 'gene' polymorphic effects and is significantly associated with increased risk with tobacco, cigarette and environmental exposure. Release and secretion of these enzymes may influence hematopoietic cell behavior and may be important in the clinical point of view. It may offer valuable tools for diagnosis and prognosis, as well as possible targets for the treatments.

Prognostic Factors and Survival in Acute Myeloid Leukemia Cases: a Report from the Northeast of Iran

  • Allahyari, Abolghasem;Tajeri, Tarane;Sadeghi, Masoud
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제17권3호
    • /
    • pp.1547-1551
    • /
    • 2016
  • Background: Acute myeloid leukemia (AML) is a clonal hematopoietic disorder resulting from genetic alterations in normal hematopoietic stem cells. The aim of this study was to evaluate prognostic factors and survival of AML patients in the Northeast of Iran. Materials and Methods: This retrospective study covered 96 patients with AML referred to Emam Reza Hospital, Mashhad city, Iran, from 2009 to 2015. Age, sex, blood group, type of AML, fever, consumption of amphotericin B, cytogenetic forms and survival were analyzed. Also, WBC, hemoglobin and platelet levels were checked. Mean follow-up was 30.5 months (60.4% mortality). Survival was plotted by GraphPad Prism 5 with Log-rank test. Results: The mean age for all AML patients at diagnosis was 40.4 years (range, 17-77 years). Some 42.7% patients were aged <35 years and 40.6% were male. In all patients, 76% had fever and 50% consumed amphotericin. T(15;17)(q22;q21) had the most prevalence (37.7%) compared to other forms. Out of 92 patients, O+(30.4%) was the most common blood group and AML-M5 (28.3%) the most common subtype. There was a significant difference in survival based on WBC and consumption of amphotericin B (P<0.05). Conclusions: WBC level, fever and consumption of amphotericin B proved to be factors for survival of AML patients. The mean age for patients in Iran is lower than other areas in the World and also survival in this study was higher than in other studies.