간암 세포주에서 黃精의 주요 성분인 Kaempferol의 성장 억제 효과
Anti-Growth Effect of Kaempferol, a Major Component of Polygonati Rhizoma, in Hepatocarcinoma Cells
0
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Recently, herbal flavonoids have been implicated for anti-cancer therapy. Flavonoids as a commonly known for their anti-oxidant activity, are contained in the herbal medicine as well as root of plants, vegetables, fruits, grains, tea, and wine. Kaempferol, a component of Polygonati rhizoma, a member of the herbal flavonoids, has been studied for anti-hypercholesterol, anti-hypertension and anti-diabetes. 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. Here, we investigated the molecular mechanism underlying kaempferol-induced anti-cancer effects using the human liver cancer cell lines, Hep3B, HepG2, and Sk-Hep-1, and human Chang liver cell as a control. As shown by the FACS analysis, measurement of caspase activity, DAPI and trypan blue staining, and DNA fragmentation assay, kaempferol induced apoptosis in the liver cancer cells with the greater potential in Hep3B cells than other liver cancer cells. In addition, we performed microarray analysis to profile the genome-wide mRNA expression regulated by kaempferol. Many of the apoptosis-related genes were significantly induced in kaempferol-treated Hep3B cells, in particular, the genes associated with MAPK cascade. Additionally, kaempferol induced the mRNA expression of genes involved in MKK7-JNK cascade, MKK3-p38 cascade, and caspase signaling pathway, which are all known to trigger apoptosis. Overall, our data suggest that kaempferol has anti-liver cancer effects by inducing apoptosis through the MKK7-JNK cascade, MKK3-p38 cascade, and caspase signaling pathways.
Abstract
Recently, herbal flavonoids have been implicated for anti-cancer therapy. Flavonoids as a commonly known for their anti-oxidant activity, are contained in the herbal medicine as well as root of plants, vegetables, fruits, grains, tea, and wine. Kaempferol, a component of Polygonati rhizoma, a member of the herbal flavonoids, has been studied for anti-hypercholesterol, anti-hypertension and anti-diabetes. 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. Here, we investigated the molecular mechanism underlying kaempferol-induced anti-cancer effects using the human liver cancer cell lines, Hep3B, HepG2, and Sk-Hep-1, and human Chang liver cell as a control. As shown by the FACS analysis, measurement of caspase activity, DAPI and trypan blue staining, and DNA fragmentation assay, kaempferol induced apoptosis in the liver cancer cells with the greater potential in Hep3B cells than other liver cancer cells. In addition, we performed microarray analysis to profile the genome-wide mRNA expression regulated by kaempferol. Many of the apoptosis-related genes were significantly induced in kaempferol-treated Hep3B cells, in particular, the genes associated with MAPK cascade. Additionally, kaempferol induced the mRNA expression of genes involved in MKK7-JNK cascade, MKK3-p38 cascade, and caspase signaling pathway, which are all known to trigger apoptosis. Overall, our data suggest that kaempferol has anti-liver cancer effects by inducing apoptosis through the MKK7-JNK cascade, MKK3-p38 cascade, and caspase signaling pathways.
참고문헌 (40)
- 문구, "암 동서의 결합치료 2", pp.309~336 (1999), 원광대학교 출판국
- "암 통계 (2009년 암종별 발생 현황, 2009년 연령군별 암발생률, 2009년 주요암 5년 생존률)" (2009), 국가암 정보센터[URL]
- 전국한의과대학 간계내과학 교수, "간계내과학 (제4판)", pp.351~367 (2001), 동양의학연구소
- 김창민, "간암의 최신지견 및 전망", 대한간학회지, 10(2), pp.113~121 (2010)
- Song, I. H., "Current status of liver diseases in Korea: Hepatocellular carcinoma", Korean J Kepatol, 15(6), pp.50~59 (2009)
- Lee, H., "Methyl gallate exhibits potent antitumor activities by inhibiting tumor infiltration of CD4+CD25+ regulatory T cells", J Immunol, 185, pp.6698~6705 (2010)
- 이연희, "An oriental herbal cocktail, ka-mi-kae-kyuk-tang, exerts anti-cancer activities by targeting angiogenesis, apoptosis and metastasis", CARCINOGENESIS, 27, pp.2455~2463, OXFORD UNIV PRESS
- Seo, I., "Ka-mi-kae-kyuk-tang oriental herbal cocktail attenuates cyclophosphamide-induced leukopenia side effects in mouse", Immunopharmacol Immunotoxicol, 33(4), pp.683~690 (2011)
- Jiang, C., "Potent antiandrogen and androgen receptor activities of an Angelica gigas-containing herbal formulation: identification of decursin as a novel and active compound with implications for prevention and treatment of prostate cancer", Cancer Res, 66, pp.453~463 (2006)
- 秦越人, "難經入門", pp.263~270 (1998), 법인문화사
- 전국한의과대학 본초학 편집위원회, "本草學", pp.651~652 (2008), 영림사
- 許浚, "東醫寶鑑", pp.1949~ (2007), 법인문화사
- 金昌玟, "中藥大辭典", pp.5082~5086 (1999), 도서출판 정담
- 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, 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, J. S., "Enzymatic preparation of kaempferol from green tea seed and its antioxidant activity", J Agric Food Chem, 54(8), pp.2951~2956 (2006)
- Miura, T., "The difference in hypoglycemic action between polygonati rhizoma and polygonati officinalis rhizoma", Biol Pharm Bull, 18(11), pp.1605~1606 (1995)
- 노승원, "黃精이 흰쥐의 식이성 고지혈증에 미치는 영향", 동의생리병리학회지, 22(5), pp.1147~1151 (2008), 대한동의병리학회
- 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)
- Singh, R., "Anti-free radical activities of kaempferol isolated from Acacia nilotica (L.) Willd", 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)
- Kang, J. W., "Kaempferol and quercetin, components of Ginkgo biloba extract (EGb 761), induce caspase-3-dependent apoptosis in oral cavity cancer cells", Phytother Res, 24(4), pp.632~ (2010)
- 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)
- Kataoka, M., "Antibacterial action of tryptanthrin and kaempferol, isolated from the indigo plant(Polygonum tinctorium Lour. ), against Helicobacter pylori-infected Mongolian gerbils", J Gastroenterol, 36(1), pp.5~9 (2001)
- Spencer, J. P, "Flavonoids : modulators of brain function?", Br J Nutr, 99, pp.60~77 (2008)
- Manach, C., "Polyphenols. food sources and bioavailability", Am J Clin Nutr, 79(5), pp.7277~7247 (2004)
- Park, S., "Huang-Lian-Jie-Du-Tang Supplemented with Schisandra chinensis Baill. and Polygonatum odoratum Druce Improved Glucose Tolerance by Potentiating Insulinotropic Actions in Islets in 90% Pancreatectomized Diabetic Rats", Biosci Biotechnol Biochem, 73(11), pp.2384~2392 (2009)
- Ahn, J., "The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways", Biochemical and Biophysical Research Communications, 373(4), pp.545~549 (2008)
- Fang, X. K., "Kaempferol and quercetin isolated from Euonymus alatus improve glucose uptake of 3T3-L1 cells without adipogenesis activity", Life Sciences, 82, pp.615~622 (2008)
- Chien, P. J., "Dietary Flavonoids Suppress Adipogenesis in 3T3-L1 Preadipocytes", Journal of Food and Drug Analysis, 13(2), pp.168~175 (2005)
- Ana Belén Granado-Serrano, "Quercetin Induces Apoptosis via Caspase Activation, Regulation of Bcl-2, and Inhibition of PI-3-Kinase", Akt and ERK Pathways in a Human Hepatoma Cell Line (HepG2), 2006, pp.136(11), 2715~2721
- Brisdelli, F., "Induction of apoptosis by quercetin : different response of human chronic myeloid(K562)and acute lymphoblastic(HSB-2)leukemia cells", Mol Cell Biochem, 296(1), pp.137~149 (2007)
- 김선희, "Quercetin Potentiates TRAIL-induced Apoptosis in Human Colon KM12 Cells", 생명과학회지, 19(9), pp.1209~1217 (2009), 한국생명과학회
- Choi, E. J., "Long-term combined administration of quercetin and daidzein inhibits quercetin-induced suppression of glutathione antioxidant defenses", Food Chem Toxicol, 43(5), pp.793~798 (2005)
- 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)
- Luo, J., "Urinary polyphenols, glutathione S-transferases copy number variation, and breast cancer risk : Results from the shanghai women's health study", Breast Cancer Res Treat, 120(3), pp.693~702 (2010)
- pyrene and flavonoids on the AhR and Nrf2-pathway in the human colon carcinoma cell line Caco-2, "Toxicol In Vitro", 2011, 671~683
- Tsai, Y. C., "Preparative chromatography of flavonoids and saponins in Gynostemma pentaphyllum and their antiproliferation effect on hepatoma cell", Phytomedicine, 18(1), pp.2~10 (2010)
- Mylonis, I., "The dietary flavonoid kaempferol effectively inhibits HIF-1 activity and hepatoma cancer cell viability under hypoxic conditions", Biochem Biophys Res Commun, 398(1), pp.74~78 (2010)