폐암세포주에서 黃精의 주요 성분인 Kaempferol의 항암 효능
Anti-tumor Effect of Kaempferol, a Component of Polygonati Rhizoma, in Lung Cancer Cells
0
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Kaempferol, a component of Polygonati rhizoma, is one of the herbal flavonoids, which is used in therapeutic agent for anti-hypercholesterol, anti-hypertension and anti-diabetes. And it is also known to be effective in anti-cancer therapy for breast, prostate and other type of cancers. However, the anti-cancer therapeutic mechanisms are pooly understood. To address molecular mechanism underlying kaempferol-induced anti-cancer effects, we determined the effect of kaempferol on cell growth of the lung cancer cell lines, A549, H1299 and H460. From the FACS analysis, measurement of caspase activity, DAPI and tryptophan blue staining, and DNA fragmentation assay, we found that kaempferol induces apoptosis and H460 cells are most sensitive among the tested cell lines. In addition, we performed microarray to identify the genome-wide expression profiling regulated by kaempferol. Lots of cell cycle-related genes were under-expressed, whereas the genes related to TGF-beta/SMAD pathway were over-expressed in kaempferol-treated H460 cells. Additionally, kaempferol also increased expression levels of apoptosis related genes such as death receptors, FAS, TRAIL-R and TNF-R, and casepase-8 and caspase-10. Overall, our results suggest that kaempferol promotes anti-lung cancer therapeutic effects by inducing G1 arrest and apoptosis through TGF-beta/SMAD pathway and death receptors/caspase pathway, respectively.
Abstract
Kaempferol, a component of Polygonati rhizoma, is one of the herbal flavonoids, which is used in therapeutic agent for anti-hypercholesterol, anti-hypertension and anti-diabetes. And it is also known to be effective in anti-cancer therapy for breast, prostate and other type of cancers. However, the anti-cancer therapeutic mechanisms are pooly understood. To address molecular mechanism underlying kaempferol-induced anti-cancer effects, we determined the effect of kaempferol on cell growth of the lung cancer cell lines, A549, H1299 and H460. From the FACS analysis, measurement of caspase activity, DAPI and tryptophan blue staining, and DNA fragmentation assay, we found that kaempferol induces apoptosis and H460 cells are most sensitive among the tested cell lines. In addition, we performed microarray to identify the genome-wide expression profiling regulated by kaempferol. Lots of cell cycle-related genes were under-expressed, whereas the genes related to TGF-beta/SMAD pathway were over-expressed in kaempferol-treated H460 cells. Additionally, kaempferol also increased expression levels of apoptosis related genes such as death receptors, FAS, TRAIL-R and TNF-R, and casepase-8 and caspase-10. Overall, our results suggest that kaempferol promotes anti-lung cancer therapeutic effects by inducing G1 arrest and apoptosis through TGF-beta/SMAD pathway and death receptors/caspase pathway, respectively.
참고문헌 (30)
- Preetha Anand, "Cancer is a Preventable Disease that Requires Major Lifestyle Changes", Pharmaceutical Research, 25(9), pp.2097~2116 (2008)
- Cho, G.J, "Current therapy of lung cancer", Korean Journal of Medicine, 62(2), pp.600~607 (2002)
- Seo, W.G., "Effects of Trichosanthes kirilowii Maxim and Scutellaria baicalensis Georgi on IL-1β-induced GnT-Ⅲ and Ⅴ in Melanoma B-16", J. of Kor. Oriental Oncology, 5(1), pp.103~118 (1999)
- Lee, H., "Methyl Gallate Exhibits Potent Antitumor Activities by Inhibiting Tumor Infiltration of CD4(+)CD25(+) Regulatory T Cells", JOURNAL OF IMMUNOLOGY, 185(11), pp.6698~6705 (2010), AMER ASSOC IMMUNOLOGISTS
- Lee, H.J., "An oriental herbal cocktail, ka-mi-kae-kyuk-tang, exerts anti-cancer activities by targeting angiogenesis, apoptosis and metastasis", CARCINOGENESIS, 27, pp.2455~2463 (2006), OXFORD UNIV PRESS
- Seo, I., "Kamikaekyuktang oriental herbal cocktail attenuates cyclophosphamide-induced leukopenia side effects in mouse", Immunopharmacol Immunotoxicol, 1~9 (2011)
- 이선구, "상백피가 A549 폐암세포주의 세포사에 미치는 영향", 동의생리병리학회지, 19(6), pp.1563~1567 (2005), 대한동의병리학회
- 유병길, "A549 폐암 세포주에 대한 ？？大棗瀉肺湯 및 ？？湯의 Apoptosis 효과", 동의생리병리학회지, 19(5), pp.1204~1212 (2005), 대한동의병리학회
- Lee, S.I, "Herbs", pp.128~129 (1983), Medical Herbal Co
- Park, J.S., "Enzymatic preparation of kaempferol from green tea seed and its antioxidant activity", J Agric Food Chem, 54(8), pp.2951~2956 (2006)
- Singh, R., "Anti-free radical activities of kaempferol isolated from Acacia nilotica (L.)", Willd. Ex. Del. Toxicol In Vitro, 22(8), pp.1965~1970 (2008)
- Gabrielska J, "Antioxidative effect of kaempferol and its equimolar mixture with phenyltin compounds on UV-irradiated liposome membranes", J Agric Food Chem, 53(1), pp.76~83 (2005)
- Parveen, Z., "Antiinflammatory and analgesic activities of Thesium chinense Turcz extracts and its major flavonoids, kaempferol and kaempferol-3-O-glucoside", Yakugaku Zasshi, 127(8), pp.1275~1279 (2007)
- Li, W., "Kaempferol induces apoptosis in human HCT116 colon cancer cells via the Ataxia-Telangiectasia Mutated-p53 pathway with the involvement of p53 Upregulated Modulator of Apoptosis", Chem Biol Interact, 177(2), pp.121~127 (2009)
- Nguyen, T.T., "Kaempferol-induced growth inhibition and apoptosis in A549 lung cancer cells is mediated by activation of MEK-MAPK", J Cell Physiol, 197, pp.110~121 (2003)
- Luo, H., "Kaempferol induces apoptosis in ovarian cancer cells through activating p53 in the intrinsic pathway", Food Chem, 128, pp.513~519 (2011)
- Jeong, J.C., "Kaempferol induces cell death through ERK and Akt-dependent down-regulation of XIAP and survivin in human glioma cells", Neurochem Res, 34, pp.991~1001 (2009)
- Spencer, J.P, "Flavonoids: modulators of brain function", Br J Nutr, 99, pp.ES60~77 (2008)
- Manach, C., "Polyphenols. food sources and bioavailability", Am J Clin Nutr, 79(5), pp.727~747 (2004)
- Miura, T., "Effect of polygonati rhizoma on blood glucose and facilitative glucose transporter isoform 2 (GLUT2) mRNA expression in Wistar fatty rats", Biol Pharm Bull, 18(4), pp.624~625 (1995)
- Kato, A., "Hypoglycemic activity of polygonati rhizoma in normal and diabetic mice", Biol Pharm Bull, 16(11), pp.1118~1120 (1993)
- 노승원, "黃精이 흰쥐의 식이성 고지혈증에 미치는 영향", 동의생리병리학회지, 22(5), pp.1147~1151 (2008), 대한동의병리학회
- Kato. A., "Suppressive effects of polygonati rhizoma on hepatic glucose output, GLUT2 mRNA expression and its protein content in rat liver", Endocr J, 41(2), pp.139~144 (1994)
- 장재식, "黃精과 Kaempferol의 지방세포 분화 억제 효과", 대한한의학회지, 31(2), pp.158~166 (2010), 대한한의학회
- Lopez-Sanchez, C., "Blood micromolar concentrations of kaempferol afford protection against ischemia", reperfusion-induced damage in rat brain, 2007, pp.1182, 123~137
- Middleton, E. Jr., "The effects of plant flavonoids on mammalian cells: implicationsfor inflammation, heart disease, and cancer", Pharmacol Rev, 52(4), pp.673~751 (2000)
- Fang, X.K., "Kaempferol and quercetin isolated from Euonymus alatus improve glucose uptake of 3T3-L1 cells without adipogenesis activity", Life Sci, 82(11), pp.615~622 (2008)
- Lee, C.J., "Effects of Betaine, Coumarin and Flavonoids on Mucin Release from Cultured Hamster Tracheal Surface Epithelial Cells", Phytotherapy Research, 18(4), pp.301~305 (2004), John Wiley & Sons Inc.
- Miean, K.H., "Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants", J Agric Food Chem, 49(6), pp.3106~3112 (2001)
- Park JS, "Enzymatic preparation of kaempferol from green tea seed and its antioxidant activity", J Agric Food Chem, 54(8), pp.2951~2956 (2006)