Effects of Oridonin on the Progress of Apoptosis in Acute Lymphoblastic Leukemia Molt-4 Cells and Its Mechanism_West China Medical Journal

Authors：

LIU Qi ^1,2 ,  WU Gang ¹ , YE Chenyi ³ , YANG Yu ² , BIE Jun ² , DENG Li. ²

1. Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China; 2. Nanchong Central Hospital, Nanchong, Sichuan 637000, P. R. China; 3. West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding?author：

WU Gang, Email: 13552919367@163.com

Keywords：

冬凌草甲素; 急性淋巴細胞白血病; 凋亡

DOI：

10.7507/1002-0179.20130262

Video：

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目的　探討冬凌草甲素（Ori）對白血病Molt-4細胞致凋亡作用及其可能的機制。方法　將不同濃度的Ori（2.5、5、10、20、40 μmol/L）作用于Molt-4細胞。采用甲基噻唑基四唑（MTT）法檢測細胞增殖，流式細胞術檢測細胞凋亡，電子顯微鏡觀察細胞凋亡超微結構的變化，Western blot方法分析凋亡相關蛋白及Caspase-3表達的變化。結果　Ori可抑制Molt-4細胞的生長及誘導凋亡，并有時間-劑量依賴性；Ori可時間依賴性的下調抗凋亡蛋白Bcl-2的表達，上調促凋亡蛋白Bax和Bim表達以及活化Caspase-3。結論　Ori可誘導Molt-4細胞凋亡，其機制可能與調節Bcl-2家族蛋白及活化Caspase-3有關。

Citation： LIU Qi,WU Gang,YE Chenyi,YANG Yu,BIE Jun,DENG Li.. Effects of Oridonin on the Progress of Apoptosis in Acute Lymphoblastic Leukemia Molt-4 Cells and Its Mechanism. West China Medical Journal, 2013, 28(6): 834-836. doi: 10.7507/1002-0179.20130262 Copy

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3.	Zhao J, Zhang M, Chen Y. Experimental research on the mechanisms of human multiple myeloma LP-1 cell apoptosis induced by oridonin[J]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2012, 32(12): 1642-1646.
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5.	Sun KW, Ma YY, Guan TP, et al. Oridonin induces apoptosis in gastric cancer through Apaf-1, cytochrome c and caspase-3 signaling pathway[J]. World J Gastroenterol, 2012, 18(48): 7166-7174.
6.	Liu Z, Ouyang L, Peng H, et al. Oridonin: targeting programmed cell death pathways as an anti-tumour agent[J]. Cell Prolif, 2012, 45(6): 499-507.
7.	Ikezoe T, Chen SS, Tong XJ, et al. Oridonin induces growth inhibition and apoptosis of a variety of human cancer cells[J]. Int J Oncol, 2003, 23(4): 1187-1193.
8.	Liu YQ, You S, Tashiro S, et al Roles of Ras and extracellular signal-regulated kinase-dependent IκBα degradation in oridonin-enhanced phagocytosis of apoptotic cells by human macrophage-like U937 cells[J]. Int Immunopharmacol, 2006, 6(2): 260-268.
9.	Zhang JF, Liu JJ, Liu PQ, et al. Oridonin inhibits cell growth by induction of apoptosis on human hepatocelluar carcinoma BEL-7402 cells[J]. Hepatol Res, 2006, 35(2): 104-110.
10.	Beauparlant P, Shore GC. Therapeutic activation of caspases in cancer: a question of selectivity[J]. Curr Opin Drug Discov Devel, 2003, 6(2): 179-187.
11.	Adams JM, Cory S. The Bcl-2 apoptotic switch in cancer development and therapy[J]. Oncogene, 2007, 26(9): 1324-1337.
12.	Ramachandran S, Desai NM, Goers TA, et al. Improved islet yields from pancreas preserved in perflurocarbon is via inhibition of apoptosis mediated by mitochondrial pathway[J]. Ame J Transp, 2006, 6(7): 1696–1703.
13.	Philchenkov AA. Caspases as regulators of apoptosis and other cell functions[J].Biochemistry (Mosc), 2003, 68(4): 365-376.
14.	Qi SN, Yoshida A, Wang ZR, et al. GP7 can induce apoptotic DNA fragmentation of human leukemia cells through caspase-3-dependent and -independent pathways[J]. Int J Mol Med, 2004, 13(1): 163-167.
15.	Donepudi M, Grutter MG. Structure and zymogen activation of caspases[J]. Biophys Chem, 2002, 101(102): 145-153.
16.	Denault JB, Salvesen GS. Caspases: keys in the ignition of cell death[J]. Chem Rev, 2002, 102(12): 4489-4500.
17.	Fischer U, Jänicke RU, Schulze-Osthoff K. Many cuts to ruin: a comprehensive update of caspase substrates[J]. Cell Death Differ, 2003, 10(1): 76-100.

1. 　Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia[J]. N Engl J Med, 2006, 354(2): 166-178.
2. 　Howard SC, Metzger ML, Wilimas JA, et al. Childhood cancer epidemiology in low-income countries[J]. Cancer, 2008, 112(3): 461-472.
3. 　Zhao J, Zhang M, Chen Y. Experimental research on the mechanisms of human multiple myeloma LP-1 cell apoptosis induced by oridonin[J]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2012, 32(12): 1642-1646.
4. 　Wang S, Zhong Z, Wan J, et al. Oridonin induces apoptosis, inhibits migration and invasion on highly-metastatic human breast cancer cells[J]. Am J Chin Med, 2013, 41(1): 177-196.
5. 　Sun KW, Ma YY, Guan TP, et al. Oridonin induces apoptosis in gastric cancer through Apaf-1, cytochrome c and caspase-3 signaling pathway[J]. World J Gastroenterol, 2012, 18(48): 7166-7174.
6. 　Liu Z, Ouyang L, Peng H, et al. Oridonin: targeting programmed cell death pathways as an anti-tumour agent[J]. Cell Prolif, 2012, 45(6): 499-507.
7. 　Ikezoe T, Chen SS, Tong XJ, et al. Oridonin induces growth inhibition and apoptosis of a variety of human cancer cells[J]. Int J Oncol, 2003, 23(4): 1187-1193.
8. 　Liu YQ, You S, Tashiro S, et al Roles of Ras and extracellular signal-regulated kinase-dependent IκBα degradation in oridonin-enhanced phagocytosis of apoptotic cells by human macrophage-like U937 cells[J]. Int Immunopharmacol, 2006, 6(2): 260-268.
9. 　Zhang JF, Liu JJ, Liu PQ, et al. Oridonin inhibits cell growth by induction of apoptosis on human hepatocelluar carcinoma BEL-7402 cells[J]. Hepatol Res, 2006, 35(2): 104-110.
10. 　Beauparlant P, Shore GC. Therapeutic activation of caspases in cancer: a question of selectivity[J]. Curr Opin Drug Discov Devel, 2003, 6(2): 179-187.
11. 　Adams JM, Cory S. The Bcl-2 apoptotic switch in cancer development and therapy[J]. Oncogene, 2007, 26(9): 1324-1337.
12. 　Ramachandran S, Desai NM, Goers TA, et al. Improved islet yields from pancreas preserved in perflurocarbon is via inhibition of apoptosis mediated by mitochondrial pathway[J]. Ame J Transp, 2006, 6(7): 1696–1703.
13. 　Philchenkov AA. Caspases as regulators of apoptosis and other cell functions[J].Biochemistry (Mosc), 2003, 68(4): 365-376.
14. 　Qi SN, Yoshida A, Wang ZR, et al. GP7 can induce apoptotic DNA fragmentation of human leukemia cells through caspase-3-dependent and -independent pathways[J]. Int J Mol Med, 2004, 13(1): 163-167.
15. 　Donepudi M, Grutter MG. Structure and zymogen activation of caspases[J]. Biophys Chem, 2002, 101(102): 145-153.
16. 　Denault JB, Salvesen GS. Caspases: keys in the ignition of cell death[J]. Chem Rev, 2002, 102(12): 4489-4500.
17. 　Fischer U, Jänicke RU, Schulze-Osthoff K. Many cuts to ruin: a comprehensive update of caspase substrates[J]. Cell Death Differ, 2003, 10(1): 76-100.

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Effects of Oridonin on the Progress of Apoptosis in Acute Lymphoblastic Leukemia Molt-4 Cells and Its Mechanism

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