• BMB Reports
• /
• 제38권6호
• /
• pp.725-738
• /
• 2005

Resistance to imatinib mesylate (also known as Gleevec, Glivec, and STI571) often becomes a barrier to the treatment of chronic myelogenous leukemia (CML). In order to identify markers of the action of imatinib mesylate, we used a mass spectrometry approach to compare protein expression profiles in human leukemia cells (K562) and in imatinib mesylate-resistant human leukemia cells (K562-R) in the presence and absence of imatinib mesylate. We identified 118 differentially regulated proteins in these two leukemia cell-lines, with and without a $1\;{\mu}M$ imatinib mesylate challenge. Nine proteins of unknown function were discovered. This is the first comprehensive report regarding differential protein expression in imatinib mesylate-treated CML cells.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2001년도 Proceedings of the Pharmaceutical Society of Korea
• /
• pp.183.1-183.1
• /
• 2001

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권9호
• /
• pp.3715-3721
• /
• 2015

Leukemia is a clonal disorder with blocked normal differentiation and cell death of hematopoietic progenitor cells. Traditional modalities with most used radiation and chemotherapy are nonspecific and toxic which cause adverse effects on normal cells. Differentiation inducing therapy forcing malignant cells to undergo terminal differentiation has been proven to be a promising strategy. However, there is still scarce of potent differentiation inducing agents. We show here that Angelica sinensis polysaccharide (ASP), a major active component in Dong quai (Chinese Angelica sinensis), has potential differentiation inducing activity in human chronic erythro-megakaryoblastic leukemia K562 cells. MTT assays and flow cytometric analysis demonstrated that ASP inhibited K562 cell proliferation and arrested the cell cycle at the G0/G1 phase. ASP also triggered K562 cells to undergo erythroid differentiaton as revealed by morphological changes, intensive benzidine staining and hemoglobin colorimetric reaction, as well as increased expression of glycophorin A (GPA) protein. ASP induced redistribution of STAT5 protein from the cytoplasm to the nucleus. Western blotting analysis further identified that ASP markedly sensitized K562 cells to exogenous erythropoietin (EPO) by activating EPO-induced JAK2/STAT5 tyrosine phosphorylation, thus augmenting the EPO-mediated JAK2/STAT5 signaling pathway. On the basis of these findings, we propose that ASP might be developed as a potential candidate for chronic myelogenous leukemia inducing differentiation treatment.

• 한국영양학회:학술대회논문집
• /
• 한국영양학회 2000년도 춘계학술대회 초록
• /
• pp.120-120
• /
• 2000

• 대한수의학회지
• /
• 제40권1호
• /
• pp.166-172
• /
• 2000

Prior to a clinical trial, the in vitro and in vivo antitumor effects of a new recombinant human interferon ${\alpha}-2a$ (rHu/IFN ${\alpha}-2a$) with/without hydroxyurea (HU) were investigated using chronic myelogenous leukemia (CML)-derived cell lines (K562 and KU812F) and BALB/c nude. mice transplanted with KU812F cells. The rHu/IFN ${\alpha}-2a$ ($10^4-10^6IU/ml$) strongly inhibited proliferation of both cell lines and the combined treatments with HU ($10{\mu}g/ml$) were more effective. In nude mice transplanted with KU812F cells. rHu/IFN ${\alpha}-2a(1{\times}10^6IU$) inhibited tumor growth by 42-65% at 15-21 days post-transplantation (DPT). The combined treatment of rHu/IFN ${\alpha}-2a (5{\times}10^5IU$) with HU (0.25mg/g b.w.) inhibited the tumor growth by 48-67% at 12-21 DPT. In addition, the treatment of rHu/IFN ${\alpha}-2a$ ($5{\times}10^6IU\;or\;1{\times}10^7IU$) rejected tumor transplantation by 40%. These results suggest that the new rHU/IFN ${\alpha}-2a$ alone or with HU is effective on CML cell lines.

• 대한한방소아과학회지
• /
• 제27권1호
• /
• pp.59-68
• /
• 2013

Objectives The aim of this study is to investigate whether hwang-ryun-haedok-tang (HDT) affect proliferations of androgen-dependent LNCaP prostate cancer cells, androgen-independent PC-3, DU-145 prostate cancer cells, MCF-7 human breast cancer cells, A549, NCI-H292 human pulmonary cancer cells and K-562 human chronic myelogenous leukemia cells. Materials and Methods Effects of HDT on proliferations of each cancer cell line were investigated. 20,000 cells/well were plated in each well of 96-well culture plate. After 24 hrs, 0.01-10% of HDT in culture medium was added to cancer cells. The number of cells was counted by using SRB assay or direct cell counting method after 72 hours from drug treatment. Effect of baicalein or berebrine on proliferation was assessed according to the same method. Results (1) HDT inhibited proliferations of LNCaP, PC-3 and DU-145 prostate cancer cells. (2) HDT inhibited proliferation of MCF-7 breast cancer cells. (3) HDT also inhibited proliferations of A549, NCI-H292 pulmonary cancer cells and K-562 chronic myelogenous leukemia cells. (4) Baicalein and berberine also showed inhibitory effects on proliferations of prostate and breast cancer cells. Conclusion : HDT inhibited proliferations of human prostate, breast, pulmonary and blood cancer cells. These results suggest us the potential use of HDT as a chemopreventive or chemotherapeutic agent. Effect of HDT on human cancer should be further investigated using in vivo experimental models that can reflect pathophysiology of human cancer through another studies.

• 생명과학회지
• /
• 제17권7호통권87호
• /
• pp.896-904
• /
• 2007

비타민 E 유도체인 $RRR-{\alpha}-tocopheryl$ succinate (vitamin E succinate, VES)는 만성골수성 백혈병 세포인 K562세포에서 apoptosis를 유도하였다. VES의 처리에 의해 apoptosis가 유도되는 과정에서 K562 세포 내의 ROS의 생성이 증가되었으며, ROS와 관련된$NF-{\kappa}B$, COX-2 그리고 $p21^{WAF1/CIP1}$등의 유전자가 활성화되었다. 뿐만 아니라, apoptosis의 과정 중 중요한 역할을 하는 Bax의 발현증가 및 손상된 DNA의 회복에 중심적 기능을 하는 PARP의 분열이 야기되었다. VES를 처리한 세포의 세포주기 분석에서는 apoptotic phase인 sub-Gl phase에서 세포사멸이 증가되고, 형태적으로는 염색질의 응축이 일어나는 결과로 미루어볼 때 VES는 K562세포의 apoptosis를 유도한 것을 알 수 있다. C57BL/C의 림프종 이종이식을 통한 VES의 항암활성 실험 결과, C57BL/C의 대조군에 비하여 종양의 성장억제를 확인하였으며 높은 생존율을 확인하였다. 이러한 결과는 백혈병 치료에 대한 분자적 기초를 제공하였으며 동물실험을 통하여 보다 실질적인 백혈병 치료의 가능성을 보여주었다.

• Biomolecules & Therapeutics
• /
• 제12권2호
• /
• pp.85-91
• /
• 2004

In all attempt to elucidate the role of apoptosis in drug resistance, cisplatin-resistant human chronic myelogenous leukemia (CML) K562 cells (K562/CDDP) were established and compared with drug sensitive parent cells (K562) in the induction of apoptosis. K562/CDDP cells were 5-fold more resistant to cisplatin compared to K562 cells. In addition, K562/CDDP cells were significantly more resistant to apoptois as judged by DNA fragmentation and DAPI staining. K562/CDDP cells exhibited decreased proleolytic activity of caspase-3 and this was further demonstrated by decreased cleavage of its substrate poly (ADP-ribose) polymerase (PARR- Western blot analysis showed that K562/CDDP cells had longer sustained levels of BCL-$X_L$ whereas no difference was noted in the level of Bcl-2. the translocation of Bax to mitochondria was significantly delayed in K562/CDDP cells. These results suggest that the reduced translocation of Bax and the sustained expression of BCL-$X_L$ may cause resistance to apoptosis through prevention of mitochondria release of cytochrome c, which subsequently induces reduction of caspase-3 activity and that this response is partly responsible for the acquired resistance to cisplatin ill K562 cells.

• Journal of Ginseng Research
• /
• 제22권3호
• /
• pp.188-192
• /
• 1998

We established the model of clonogenic assay with human tumor cell line such as Calu-3 (lung carcinoma), HEC- lB (endometrial adenocarcinoma) , HEp-2 (larnyx carcinoma), Hs-5787 (breast carcinoma), K-562 (chronic myelogenous leukemia), SF-188 (brain carcinoma), SNU-1 (stomach carcinoma) and WiDr (colon carcinoma) . We investigated growth inhibition of solvent (EtOH, MeOH) and water (100$^{\circ}C$, 121$^{\circ}C$) extracts from Korean red ginseng by clonogenic assay. The results of clonogenic assay showed that EtOH extract had growth inhibition against Calu-3, SF-188 and SNU-1, MeOH extract had growth inhibition against Calu-3, Hs-5787, K-562, and WiDr, but water extract at 100$^{\circ}C$ and water extract at 121$^{\circ}C$ had not growth inhibition against used cell lines.

• 한국식품과학회지
• /
• 제31권4호
• /
• pp.1065-1070
• /
• 1999

참취뿌리의 에탄올 추출물과 용매 분획물에 대한 생리활성 효과를 밝히기 위해 항돌연변이성 및 암세포 성장억제효과를 실시한 결과 에탄올 추출물 자체의 돌연변이성은 없었다. 직접변이원인 N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)에 대해서는 Salmonella typhimurium TA100의 경우 에탄올 추출물이 79%, 에틸아세테이트 분획물은 82%의 억제효과를 나타내었다. 4-Nitroquinoline-1-oxide(4NQO)에 대해서는 Salmonella typhimurium TA98에서 에탄올 추출물이 48%, 에틸 아세테이트 분획물은 60%의 억제효과를 보였다. 한편 간접 변이원인 benzo(${\alpha}$)pyrene[B(${\alpha}$)P]에 대해서는 에틸아세테이트 분획물의 경우 TA98에서는 78%, TA100에서는 85%의 높은 억제활성을 나타내었다. 그리고 3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole(Trp-P-1)에 대해서는 TA98에서 89%의 높은 억제효과를 보였다. 한편 참취 에탄올 추출물에 대한 암세포 성장억제 실험에서도 chronic myelogenous leukemia (K562), human gastric carcinoma (KATOIII), human hepatocellular carcinoma (Hep3B) 및 human breast adenocarcioma (MCF-7)에 대하여 높은 세포독성을 나타내었으며 용매 분획물의 경우 KATOIII 세포에서는 모든 분획물이 높은 세포독성을 나타내었으나 그외세포에 대해서는 물분획물을 제외한 에틸아세테이트, 부탄올 및 클로로포름 분획물이 높은 세포독성을 나타내었다.