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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2017.7
- 수록면
- 247 - 256 (10page)
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초록· 키워드
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Background: KG-135, a standardized formulation enriched with Rk1, Rg3, and Rg5 ginsenosides, has been shown to inhibit various types of cancer cells; however, the underlying mechanisms are not fully understood. In this study, we explored its effects in A549 human lung cancer cells to investigate the induction of Forkhead Class box O3a (FOXO3a) and autophagy.
Methods: Cell viability was determined by sulforhodamine B staining. Apoptosis and cell cycle distribution were analyzed using flow cytometry. The changes of protein levels were determined using Western blot analysis. Autophagy induction was monitored by the formation of acidic vesicular organelles stained with acridine orange.
Results: KG-135 effectively arrested the cells in G1 phase with limited apoptosis. Accordingly, a decrease of cyclin-dependent kinase-4, cyclin-dependent kinase-6, cyclin D1, and phospho-retinoblastoma protein, and an increase of p27 and p18 proteins were observed. Intriguingly, KG-135 increased the tumor suppressor FOXO3a and induced the accumulation of autophagy hallmark LC3-II and acidic vesicular organelles without an increase of the upstream marker Beclin-1. Unconventionally, the autophagy adaptor protein p62 (sequestosome 1) was increased rather than decreased. Blockade of autophagy by hydroxychloroquine dramatically potentiated KG-135-induced FOXO3a and its downstream (FasL) ligand accompanied by the cleavage of caspase-8. Meanwhile, the decrease of Bcl-2 and survivin, as well as the cleavage of caspase-9, were also drastically enhanced, resulting in massive apoptosis.
Conclusion: Besides arresting the cells in G1 phase, KG-135 increased FOXO3a and induced an unconventional autophagy in A549 cells. Both the KG-135-activated extrinsic FOXO3a/FasL/caspase-8 and intrinsic caspase-9 apoptotic pathways were potentiated by blockade of autophagy. Combination of KG-135 and autophagy inhibitor may be a novel strategy as an integrative treatment for cancers.
Methods: Cell viability was determined by sulforhodamine B staining. Apoptosis and cell cycle distribution were analyzed using flow cytometry. The changes of protein levels were determined using Western blot analysis. Autophagy induction was monitored by the formation of acidic vesicular organelles stained with acridine orange.
Results: KG-135 effectively arrested the cells in G1 phase with limited apoptosis. Accordingly, a decrease of cyclin-dependent kinase-4, cyclin-dependent kinase-6, cyclin D1, and phospho-retinoblastoma protein, and an increase of p27 and p18 proteins were observed. Intriguingly, KG-135 increased the tumor suppressor FOXO3a and induced the accumulation of autophagy hallmark LC3-II and acidic vesicular organelles without an increase of the upstream marker Beclin-1. Unconventionally, the autophagy adaptor protein p62 (sequestosome 1) was increased rather than decreased. Blockade of autophagy by hydroxychloroquine dramatically potentiated KG-135-induced FOXO3a and its downstream (FasL) ligand accompanied by the cleavage of caspase-8. Meanwhile, the decrease of Bcl-2 and survivin, as well as the cleavage of caspase-9, were also drastically enhanced, resulting in massive apoptosis.
Conclusion: Besides arresting the cells in G1 phase, KG-135 increased FOXO3a and induced an unconventional autophagy in A549 cells. Both the KG-135-activated extrinsic FOXO3a/FasL/caspase-8 and intrinsic caspase-9 apoptotic pathways were potentiated by blockade of autophagy. Combination of KG-135 and autophagy inhibitor may be a novel strategy as an integrative treatment for cancers.
목차
ABSTRACT
1. Introduction
2. Materials and methods
3. Results
4. Discussion
References
참고문헌 (43)
참고문헌 신청
[학술지(정기간행물)] - Xiang YZ / 2008 / A comparison of the ancient use of ginseng in traditional Chinese medicine with modern pharmacological experiments and clinical trials / Phytother Res 22 : 851 ~ 858
[학술지(정기간행물)] - Choi KT / 2008 / Botanical characteristics, pharmacological effects and medicinal components of Korean Panax ginseng Meyer / Acta Pharmacol Sin 29 : 1109 ~ 1118
[학술지(정기간행물)] - Wong AS / 2015 / Recent advances in ginseng as cancer therapeutics : a functional and mechanistic overview / Nat Prod Rep 32 : 256 ~ 272
[학술지(정기간행물)] - Hyuck Jae Choi / 2012 / Protective Effect of Heat-processed Ginseng (Sun Ginseng) in the Adenine-induced Renal Failure Rats / Journal of Ginseng Research 36 (3) : 270 ~ 276
[학술지(정기간행물)] - Lee WH / 2009 / Heat-processed neoginseng, KG-135, down-regulates G1 cyclin-dependent kinase through the proteasome-mediated pathway in HeLa cells / Oncol Rep 21 : 467 ~ 474
[학술지(정기간행물)] - Choi KT / 2008 / Botanical characteristics, pharmacological effects and medicinal components of Korean Panax ginseng Meyer / Acta Pharmacol Sin 29 : 1109 ~ 1118
[학술지(정기간행물)] - Wong AS / 2015 / Recent advances in ginseng as cancer therapeutics : a functional and mechanistic overview / Nat Prod Rep 32 : 256 ~ 272
[학술지(정기간행물)] - Hyuck Jae Choi / 2012 / Protective Effect of Heat-processed Ginseng (Sun Ginseng) in the Adenine-induced Renal Failure Rats / Journal of Ginseng Research 36 (3) : 270 ~ 276
[학술지(정기간행물)] - Lee WH / 2009 / Heat-processed neoginseng, KG-135, down-regulates G1 cyclin-dependent kinase through the proteasome-mediated pathway in HeLa cells / Oncol Rep 21 : 467 ~ 474
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UCI(KEPA) : I410-ECN-0101-2018-524-001598936