Original Article

Korean J Hematol 2008; 43(1):

Published online March 30, 2008

https://doi.org/10.5045/kjh.2008.43.1.19

© The Korean Society of Hematology

NF-ՊB의 활성화 억제기전을 통한 Curcumin의 U266 다발성골수종 세포주의 성장 억제효과

박주원, 안광성, 배은경, 김진호, 정승현, 김병수, 김대영, 김병국, 이영열, 윤성수

서울대학교 의과대학 암연구소, 내과학교실,
서울대학교병원 임상의학연구소,
한양대학교병원 혈액종양학과, 오뚜기 중앙연구소

Abrogation of U266 Multiple Myeloma Cell Proliferation Via Inhibition of NF-ՊB Activation by Curcumin

Ju won Park, Kwang Sung Ahn, Eun Kyung Bae, Jin Ho Kim, Seung Hyeon Jung, Byung Su Kim, Dae Young Kim, Byoung Kook Kim, Young Yiul Lee, Sung Soo Yoon

Cancer Research Institute, Seoul National University College of Medicine
Department of Internal Medicine, Seoul National University College of Medicine
Clinical Research Institute, Seoul National University Hospital, Section of Hematology/Oncology
Hanyang University Hospital, Seoul
Ottogi Research Center, Anyang, Korea

Abstract

Background:
Curcumin is a naturally occurring biologically active compound, and it has been shown to possess potent anti-inflammatory, anti-tumor and anti-oxidative properties. It is known for its anti-proliferative and proapoptotic effects in several cancer cells. Curcumin's effects on the mechanisms of cell survival and the expression of various cytokines were investigated in U266 cells and the in vivo effects of curcumin were examined using an animal model.
Methods:
Cell proliferation assay and flow cytometry were used to examine cell proliferation, along with cell cycle analysis. The protein expressions were analyzed by Western blotting and the expressed levels of cytokines were analyzed by the ELISA method.
Results:
Curcumin inhibited U266 cell growth in a dose-dependent and time-dependent manner. Cell cycle analysis showed an increased sub-G1 phase, a down regulated cyclinD1 expression and an induced p21 expression. Apoptosis induced a down regulated procaspase 3 expression and it induced cleaved PARP. Curcumin inhibited the IL (interleukin)-6 induced cell signal pathway via decreasing the STAT1 an 3, Erk cyclinD1 and c-myc expressions. Also, administration of 25mg/kg curcumin to a U266 animal model inhibited cancer cell engraftment in the bone marrow and it decreased the IL-6, sIL-6R and IL-8 expression levels.
Conclusion:
Curcumin induced cell cycle arrest and apoptosis and it inhibited the IL-6 mediated signal transduction pathways in U266 cells. Similar to the in vitro results, curcumin inhibited cancer cell proliferation and the expression of cytokine in vivo.

Keywords Curcumin, 6-aminoquinazoline, Multiple myeloma, Animal model, IL-6, sIL-6R

Article

Original Article

Korean J Hematol 2008; 43(1): 19-27

Published online March 30, 2008 https://doi.org/10.5045/kjh.2008.43.1.19

Copyright © The Korean Society of Hematology.

NF-ՊB의 활성화 억제기전을 통한 Curcumin의 U266 다발성골수종 세포주의 성장 억제효과

박주원, 안광성, 배은경, 김진호, 정승현, 김병수, 김대영, 김병국, 이영열, 윤성수

서울대학교 의과대학 암연구소, 내과학교실,
서울대학교병원 임상의학연구소,
한양대학교병원 혈액종양학과, 오뚜기 중앙연구소

Abrogation of U266 Multiple Myeloma Cell Proliferation Via Inhibition of NF-ՊB Activation by Curcumin

Ju won Park, Kwang Sung Ahn, Eun Kyung Bae, Jin Ho Kim, Seung Hyeon Jung, Byung Su Kim, Dae Young Kim, Byoung Kook Kim, Young Yiul Lee, Sung Soo Yoon

Cancer Research Institute, Seoul National University College of Medicine
Department of Internal Medicine, Seoul National University College of Medicine
Clinical Research Institute, Seoul National University Hospital, Section of Hematology/Oncology
Hanyang University Hospital, Seoul
Ottogi Research Center, Anyang, Korea

Abstract

Background:
Curcumin is a naturally occurring biologically active compound, and it has been shown to possess potent anti-inflammatory, anti-tumor and anti-oxidative properties. It is known for its anti-proliferative and proapoptotic effects in several cancer cells. Curcumin's effects on the mechanisms of cell survival and the expression of various cytokines were investigated in U266 cells and the in vivo effects of curcumin were examined using an animal model.
Methods:
Cell proliferation assay and flow cytometry were used to examine cell proliferation, along with cell cycle analysis. The protein expressions were analyzed by Western blotting and the expressed levels of cytokines were analyzed by the ELISA method.
Results:
Curcumin inhibited U266 cell growth in a dose-dependent and time-dependent manner. Cell cycle analysis showed an increased sub-G1 phase, a down regulated cyclinD1 expression and an induced p21 expression. Apoptosis induced a down regulated procaspase 3 expression and it induced cleaved PARP. Curcumin inhibited the IL (interleukin)-6 induced cell signal pathway via decreasing the STAT1 an 3, Erk cyclinD1 and c-myc expressions. Also, administration of 25mg/kg curcumin to a U266 animal model inhibited cancer cell engraftment in the bone marrow and it decreased the IL-6, sIL-6R and IL-8 expression levels.
Conclusion:
Curcumin induced cell cycle arrest and apoptosis and it inhibited the IL-6 mediated signal transduction pathways in U266 cells. Similar to the in vitro results, curcumin inhibited cancer cell proliferation and the expression of cytokine in vivo.

Keywords: Curcumin, 6-aminoquinazoline, Multiple myeloma, Animal model, IL-6, sIL-6R

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