인동덩굴로부터 분리된 Cynaroside이 Doxorubicin으로 유도된 인간 근위세뇨관 HK-2 세포의 괴사에 미치는 저해 효과
Inhibitory Effect of Cynaroside Isolated from Lonicera japonia Thunb on Doxorubicin-induced Necrosis in Human Renal Proximal Tubular HK-2 Cells
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Background: Cynaroside is a flavone, a flavonoid-like compound, known by different names (luteoloside and cinaroside). It is commonly found in Lonicera japonica Thunb., Chrysanthemum moriflium, and Angelica keiskei. The process of cell death has been classified as necrosis and apoptosis. Necrosis refers to unregulated cell death induced by a chemotherapeutic agent. Doxorubicin is an anthracycline anti-cancer drug used to treat acute leukemia, cancer, and lymphoma. However, it induces nephrotoxicity including tubular damage. Therefore, we investigated the protective effect of cynaroside against doxorubicin-induced necrosis in HK-2 cells. Methods and Results: To confirm the beneficial effect of cynaroside on doxorubicin-induced necrosis, HK-2 cells, a human proximal tubule epithelial cell line were treated with 10 μM doxorubicin and 80 μM cynaroside. Doxorubicin treatment resulted in increased DNA fragmentation, caspase-3 activity and mitochondria hyperactivation during cell necrosis. However, pretreatment with 80 μM cynaroside attenuated DNA fragmentation, caspase-3 activity and mitochondria hyperactivation induced by 10 μM doxorubicin in HK-2 cells. Conclusions: These results indicated that pretreatment with cynaroside ameliorated doxorubicin-induced necrosis in HK-2 cells. Therefore, cynaroside be used as a therapeutic agent for improving doxorubicin-induced nephrotoxicity. However, further studies are required to evaluated the toxicity of cynaroside treatment in animals and to determine its protective effect against doxorubicininduced nephrotoxicity in an animal model.
Abstract
Background: Cynaroside is a flavone, a flavonoid-like compound, known by different names (luteoloside and cinaroside). It is commonly found in Lonicera japonica Thunb., Chrysanthemum moriflium, and Angelica keiskei. The process of cell death has been classified as necrosis and apoptosis. Necrosis refers to unregulated cell death induced by a chemotherapeutic agent. Doxorubicin is an anthracycline anti-cancer drug used to treat acute leukemia, cancer, and lymphoma. However, it induces nephrotoxicity including tubular damage. Therefore, we investigated the protective effect of cynaroside against doxorubicin-induced necrosis in HK-2 cells. Methods and Results: To confirm the beneficial effect of cynaroside on doxorubicin-induced necrosis, HK-2 cells, a human proximal tubule epithelial cell line were treated with 10 μM doxorubicin and 80 μM cynaroside. Doxorubicin treatment resulted in increased DNA fragmentation, caspase-3 activity and mitochondria hyperactivation during cell necrosis. However, pretreatment with 80 μM cynaroside attenuated DNA fragmentation, caspase-3 activity and mitochondria hyperactivation induced by 10 μM doxorubicin in HK-2 cells. Conclusions: These results indicated that pretreatment with cynaroside ameliorated doxorubicin-induced necrosis in HK-2 cells. Therefore, cynaroside be used as a therapeutic agent for improving doxorubicin-induced nephrotoxicity. However, further studies are required to evaluated the toxicity of cynaroside treatment in animals and to determine its protective effect against doxorubicininduced nephrotoxicity in an animal model.
참고문헌 (22)
- Arif IS, "Increasing doxorubicin activity against breast cancer cells using PPARγ-ligands and by exploiting circadian rhythms", British Journal of Pharmacology, 169, pp.1178~1188 (2013)
- 최소라, "추출용매와 부위에 따른 고추 추출물의 세포독성", 한국약용작물학회지, 22(5), pp.369~377 (2014), 한국약용작물학회[DOI]
- Dranitsaris G, "Advances in cancer therapeutics and patient access to new drugs", PharmacoEconomics, 29, pp.213~224 (2011)
- Fink SL, "Apoptosis, pyroptosis, and necrosis : Mechanistic description of dead and dying eukarytic cells", Infection and Immunity, 73, pp.1907~1916 (2005)
- Finn GJ, "In vitro cytotoxic potential and mechanism of action of selected coumarins, using human renal cell lines", Cancer Letters, 183, pp.61~68 (2002)
- 한혜민, "마름 추출물의 항산화활성 및 암세포증식 억제 활성", 한국약용작물학회지, 24(1), pp.14~20 (2016), 한국약용작물학회[DOI]
- 고운철, "미성숙 진귤 과피 추출물이 신경세포 사멸에 미치는 영향", 한국약용작물학회지, 23(2), pp.144~149 (2015), 한국약용작물학회[DOI]
- Kopp F, "miR-200c sensitizes breast cancer cells to doxorubicin treatment by decreasing TrkB and Bmi1 expression", Plos One, pp.1~17 (2012)
- Leibundgut G, "Drug treatment of chronic heart failure in the elderly", Drugs and Aging, 24, pp.991~1006 (2007)
- Los M, "Activation and caspase-mediated inhibition of PARP : A molecular switch between fibroblast necrosis and apoptosis in death receptor signaling", Molecular Biology of the Cell, 13, pp.978~988 (2002)
- Lüpertz R, "The forkhead trascription factor FOXO4sensitizes cancer cells to doxorubicn-mediated cytotoxicity", Carcinogenesis, 29, pp.2045~2052 (2008)
- Nikoletopoulou V, "Crosstalk between apoptosis, necrosis and autophagy", Biochimica et Biophysica Acta, 1833, pp.3448~3459 (2013)
- Octavia Y, "Doxorubicin-induced cardiomyopathy;From molecular mechanisms to therapeutic strategies", Journal of Molecular and Cellular Cardiology, 52, pp.1213~1225 (2012)
- Park JC, "Effects of extract from Angelica keiskei and its component, cynaroside, on the hepatic bromobenzenemetabolizing enzyme system in rats", Phytotherapy Research, 16, pp.24~27 (2002)
- Shin HJ, "Doxorubicin-induced necrosis is mediated by poly(ADP-ribose) polymerase 1(PARP1) but is independent of p53", Scientific reports, 5, pp.15798~ (2015)
- Sun X, "Protective effects of cynaroside against H2O2-induced apoptosis in H9c2 cardiomyoblasts", Journal of Cellular Biochemistry, 112, pp.2019~2029 (2011)
- Tacar O, "Doxorubicin : An update on anticancer molecular action, toxicity and novel drug delivery systems", Journal of Pharmacy and Pharmacology, 65, pp.157~170 (2013)
- Thorn CF, "Doxorubicin pathways : Pharmacodynamics and adverse effects", Pharmacogenet Genomics, 21, pp.440~446 (2011)
- Wen HU, "Effects of ultrahigh pressure extraction on yield and antioxidant activity of chlorogenic acid and cynaroside extracted from flower bubs of Lonicera japonica", Chiness Journal of Natural Medicines, 13, pp.445~453 (2015)
- Jinfeng Yang, "Antioxidant and Anticancer Properties of the Extracts from Lepisorus thunbergianus (Kaulf.) Ching", 한국약용작물학회지, 23(4), pp.324~333 (2015), 한국약용작물학회[DOI]
- 윤군애, "자귀나무(Albizzia julibrissin)의 물 추출물과 Doxorubicin 혼용의 마우스 Sarcoma에 대한 항암상승효과", 대한암예방학회지, 17(3), pp.239~243 (2012), 대한암예방학회
- 윤지혜, "마우스 정모세포주에서 스티렌에 대한 삼백초 에탄올 추출물의 보호 효과", 한국약용작물학회지, 25(1), pp.45~51 (2017), 한국약용작물학회[DOI]