Research progress on anti-tumor mechanisms of dihydroartemisinin

ZHOU Xuwei; TAN Weifeng; XIE Fangyuan; XIN Bao; CHEN Jun

doi:10.3969/j.issn.1006-0111.2019.03.003

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Article Navigation > Journal of Pharmaceutical Practice and Service > 2019 > 37(3): 206-211,278

ZHOU Xuwei, TAN Weifeng, XIE Fangyuan, XIN Bao, CHEN Jun. Research progress on anti-tumor mechanisms of dihydroartemisinin[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(3): 206-211,278. doi: 10.3969/j.issn.1006-0111.2019.03.003

Citation:

ZHOU Xuwei, TAN Weifeng, XIE Fangyuan, XIN Bao, CHEN Jun. Research progress on anti-tumor mechanisms of dihydroartemisinin[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(3): 206-211,278. doi: 10.3969/j.issn.1006-0111.2019.03.003

Research progress on anti-tumor mechanisms of dihydroartemisinin

doi: 10.3969/j.issn.1006-0111.2019.03.003

1.
Department of Pharmacy, Eastern Hepatobiliary Surgery Hospital Affiliated to Naval Medical University, Shanghai 200438, China
2.
Department of Biliary Tract Surgery(Ⅳ), Eastern Hepatobiliary Surgery Hospital Affiliated to Naval Medical University, Shanghai 200438, China

Received Date: 2018-09-28
Rev Recd Date: 2019-01-25

Abstract

Dihydroartemisinin(DHA),an important artemisinin derivative,is one of new anti-malarial medicines developed by Chinese scientists.In recent years,it was reported that DHA is a promising anti-cancer medicine besides its extraordinary antimalarial activities.This article overviews the mechanisms,targets and signaling pathways of DHA based on the recent studies published in English and Chinese literatures.Specifically,this article covers some important topics,such as apoptosis,endoplasmic reticulum stress,the growth,proliferation and invasion of cancer cells,multidrug resistance and oxidative damage,in order to provide a better understanding to the anti-cancer effects of DHA and information for new drug development and design.
- dihydroartemisinin,
- tumor,
- mechanisms

References

[1]	WONG Y K,XU C,KALESH K A,et al.Artemisinin as an anticancer drug:recent advances in target profiling and mechanisms of action[J].Med Res Rev,2017,37(6):1492-1517.
[2]	郭宗儒.青蒿素类抗疟药的研制[J].药学学报,2016,51(1):157-164.
[3]	LU J J,MENG L H,SHANKAVARAM U T,et al.Dihydroartemisinin accelerates c-MYC oncoprotein degradation and induces apoptosis in c-MYC-overexpressing tumor cells[J].Biochem Pharmacol,2010,80(1):22-30.
[4]	LIANG S,SUN K,WANG Y,et al.Role of Cyt-C/caspases-9,3,Bax/Bcl-2 and the FAS death receptor pathway in apoptosis induced by zinc oxide nanoparticles in human aortic endothelial cells and the protective effect by alpha-lipoic acid[J].Chem Biol Interact,2016,258:40-51.
[5]	HE Q,SHI J,SHEN X L,et al.Dihydroartemisinin upregulates death receptor 5 expression and cooperates with TRAIL to induce apoptosis in human prostate cancer cells[J].Cancer Biol Ther,2010,9(10):819-824.
[6]	KONG R,JIA G,CHENG Z X,et al.Correction:dihydroartemisinin enhances Apo2L/TRAIL-mediated apoptosis in pancreatic cancer cells via ROS-mediated up-regulation of death receptor 5[J].Plos ONE,2012,7(5):e37222.
[7]	LI Y W,ZHANG W,XU N,et al.Dihydroartemisinin inhibits proliferation of pancreatic cancer JF-305 cells by regulating expression of apoptosis related proteins and production of reactive oxygen species[J].Zhongguo Zhong Yao Za Zhi,2017,42(15):3026-3030.
[8]	ZUO Z J,WANG S T,JIANG L X,et al.Effect of dihydroartemisinin combined irradiation on the apoptosis of human lung cancer GLC-82 cells and its mechanism study[J].Zhongguo Zhong XI Yi Jie He Za Zhi,2014,34(10):1220-1224.
[9]	LU M,SUN L,ZHOU J,et al.Dihydroartemisinin-induced apoptosis is associated with inhibition of sarco/endoplasmic reticulum calcium ATPase activity in colorectal cancer[J].Cell Biochem Biophys,2015,73(1):137-145.
[10]	QIN G,ZHAO C,ZHANG L,et al.Dihydroartemisinin induces apoptosis preferentially via a Bim-mediated intrinsic pathway in hepatocarcinoma cells[J].Apoptosis,2015,20(8):1072-1086.
[11]	LIAO K,LI J,WANG Z.Dihydroartemisinin inhibits cell proliferation via AKT/GSK3β/cyclinD1 pathway and induces apoptosis in A549 lung cancer cells[J].Int J Clin Exp Pathol,2014,7(12):8684.
[12]	FASANO E,SERINI S,PICCIONI E,et al.DHA induces apoptosis by altering the expression and cellular location of GRP78 in colon cancer cell lines[J].Biochim Biophys Acta,2012,1822(11):1762-1772.
[13]	CHEN S S,HU W,WANG Z,et al.p8 attenuates the apoptosis induced by dihydroartemisinin in cancer cells through promoting autophagy[J].Cancer Biol Ther,2015,16(5):770-779.
[14]	CHEN M,CHEN T S,LU Y Y,et al.Dihydroarteminsin-induced apoptosis is not dependent on the translocation of Bim to the endoplasmic reticulum in human lung adenocarcinoma cells[J].Pathol Oncol Res,2012,18(4):809-816.
[15]	ZHANG C,SYED T W,LIU R,et al.Role of endoplasmic reticulum stress,autophagy,and inflammation in cardiovascular disease[J].Front Cardiovasc Med,2017,4:29.
[16]	DU X X,LI Y J,WU C L,et al.Initiation of apoptosis,cell cycle arrest and autophagy of esophageal cancer cells by dihydroartemisinin[J].Biomed Pharmac,2013,67(5):417-424.
[17]	MARCINIAK S J,RON D.Endoplasmic reticulum stress signaling in disease[J].Physiol Rev,2006,86(4):1133-1149.
[18]	SCHRÖDER M.Endoplasmic reticulum stress responses[J].Cell Mol Life Sci,2008,65(6):862-894.
[19]	WANG M,KAUFMAN R J.Protein misfolding in the endoplasmic reticulum as a conduit to human disease[J].Nature,2016,529(7586):326-335.
[20]	HANAHAN D,WEINBERG R A.Hallmarks of cancer:the next generation[J].Cell,2011,144(5):646-674.
[21]	INGHAM M,SCHWARTZ G K.Biology of neoplasia:cell-cycle therapeutics come of age[J].J Clin Oncol,2017,35(25):2949-2959.
[22]	MAGENTA D,SANGIOVANNI E,BASILICO N,et al.Inhibition of metalloproteinase-9 secretion and gene expression by artemisinin derivatives[J].Acta Trop,2014,140:77-83.
[23]	LIN R,ZHANG Z,CHEN L,et al.Dihydroartemisinin (DHA) induces ferroptosis and causes cell cycle arrest in head and neck carcinoma cells[J].Cancer Lett,2016,381(1):165-175.
[24]	TONG Y,LIU Y,ZHENG H,et al.Artemisinin and its derivatives can significantly inhibit lung tumorigenesis and tumor metastasis through Wnt/β-catenin signaling[J].Oncotarget,2016,7(21):31413-31428.
[25]	MI Y,GENG G,ZOU Z,et al.Dihydroartemisinin inhibits glucose uptake and cooperates with glycolysis inhibitor to induce apoptosis in non-small cell lung carcinoma cells[J].PloS ONE,2015,10(3):e0120426.
[26]	ALASEEM A,ALHAZZANI K,Dondapati P,et al.Matrix metalloproteinases:a challenging paradigm of cancer management[J].Semin Cancer Biol,2017,Epub.
[27]	SHAO Y Y,ZHANG T L,WU L X,et al.AKT Axis,miR-21,and RECK play pivotal roles in dihydroartemisinin killing malignant glioma cells[J].Int J Mol Sci,2017,18(2):350.
[28]	HWANG Y P,YUN H J,KIM H G,et al.Suppression of PMA-induced tumor cell invasion by dihydroartemisinin via inhibition of PKCalpha/Raf/MAPKs and NF-kappaB/AP-1-dependent mechanisms[J].Biochem Pharmacol,2010,79(12):1714-1726.
[29]	HU C J,ZHOU L,CAI Y.Dihydroartemisinin induces apoptosis of cervical cancer cells via upregulation of RKIP and downregulation of bcl-2[J].Cancer Biol Ther,2014,15(3):279-288.
[30]	CHEN J,CHEN X,WANG F,et al.Dihydroartemisinin suppresses glioma proliferation and invasion via inhibition of the ADAM17 pathway[J].Neurol Sci,2015,36(3):435-440.
[31]	WANG S J,SUN B,CHENG Z X,et al.Dihydroartemisinin inhibits angiogenesis in pancreatic cancer by targeting the NF-κB pathway[J].Cancer Chemother Pharmacol,2011,68(6):1421.
[32]	PILATI P,NITTI D,MOCELLIN S.Cancer resistance to type Ⅱ topoisomerase inhibitors[J].Curr Med Chem,2012,19(23):3900-3906.
[33]	WIJDEVEN R H,PANG B,ASSARAF Y G,et al.Old drugs,novel ways out:Drug resistance toward cytotoxic chemotherapeutics[J].Drug Resist Updat,2016,28:65-81.
[34]	ONTIKATZE T,RUDNER J,HANDRICK R,et al.Dihydroartemisinin is a hypoxia-active anti-cancer drug in colorectal carcinoma cells[J].Front Oncol,2014,4:116.
[35]	CARO J T,MARíN L M,IAZBIK M C,et al.Markers of iron metabolism in retired racing greyhounds with and without osteosarcoma[J].Vet Clin Pathol,2013,42(3):360-363.
[36]	JIA L,SONG Q,ZHOU C,et al.Dihydroartemisinin as a putative STAT3 inhibitor,suppresses the growth of head and neck squamous cell carcinoma by targeting Jak2/STAT3 signaling[J].PloS ONE,2016,11(1):e0147157.
[37]	CAO L,DUANMU W,YIN Y,et al.Dihydroartemisinin exhibits anti-glioma stem cell activity through inhibiting p-AKT and activating caspase-3[J].Pharmazie,2014,69(10):752-758.

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通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

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Research progress on anti-tumor mechanisms of dihydroartemisinin

1. Department of Pharmacy, Eastern Hepatobiliary Surgery Hospital Affiliated to Naval Medical University, Shanghai 200438, China

2. Department of Biliary Tract Surgery(Ⅳ), Eastern Hepatobiliary Surgery Hospital Affiliated to Naval Medical University, Shanghai 200438, China

Received Date: 2018-09-28

Rev Recd Date: 2019-01-25

Key words:

dihydroartemisinin /
tumor /
mechanisms

Abstract: Dihydroartemisinin(DHA),an important artemisinin derivative,is one of new anti-malarial medicines developed by Chinese scientists.In recent years,it was reported that DHA is a promising anti-cancer medicine besides its extraordinary antimalarial activities.This article overviews the mechanisms,targets and signaling pathways of DHA based on the recent studies published in English and Chinese literatures.Specifically,this article covers some important topics,such as apoptosis,endoplasmic reticulum stress,the growth,proliferation and invasion of cancer cells,multidrug resistance and oxidative damage,in order to provide a better understanding to the anti-cancer effects of DHA and information for new drug development and design.

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Reference (37)

[1]	WONG Y K,XU C,KALESH K A,et al.Artemisinin as an anticancer drug:recent advances in target profiling and mechanisms of action[J].Med Res Rev,2017,37(6):1492-1517.
[2]	郭宗儒.青蒿素类抗疟药的研制[J].药学学报,2016,51(1):157-164.
[3]	LU J J,MENG L H,SHANKAVARAM U T,et al.Dihydroartemisinin accelerates c-MYC oncoprotein degradation and induces apoptosis in c-MYC-overexpressing tumor cells[J].Biochem Pharmacol,2010,80(1):22-30.
[4]	LIANG S,SUN K,WANG Y,et al.Role of Cyt-C/caspases-9,3,Bax/Bcl-2 and the FAS death receptor pathway in apoptosis induced by zinc oxide nanoparticles in human aortic endothelial cells and the protective effect by alpha-lipoic acid[J].Chem Biol Interact,2016,258:40-51.
[5]	HE Q,SHI J,SHEN X L,et al.Dihydroartemisinin upregulates death receptor 5 expression and cooperates with TRAIL to induce apoptosis in human prostate cancer cells[J].Cancer Biol Ther,2010,9(10):819-824.
[6]	KONG R,JIA G,CHENG Z X,et al.Correction:dihydroartemisinin enhances Apo2L/TRAIL-mediated apoptosis in pancreatic cancer cells via ROS-mediated up-regulation of death receptor 5[J].Plos ONE,2012,7(5):e37222.
[7]	LI Y W,ZHANG W,XU N,et al.Dihydroartemisinin inhibits proliferation of pancreatic cancer JF-305 cells by regulating expression of apoptosis related proteins and production of reactive oxygen species[J].Zhongguo Zhong Yao Za Zhi,2017,42(15):3026-3030.
[8]	ZUO Z J,WANG S T,JIANG L X,et al.Effect of dihydroartemisinin combined irradiation on the apoptosis of human lung cancer GLC-82 cells and its mechanism study[J].Zhongguo Zhong XI Yi Jie He Za Zhi,2014,34(10):1220-1224.
[9]	LU M,SUN L,ZHOU J,et al.Dihydroartemisinin-induced apoptosis is associated with inhibition of sarco/endoplasmic reticulum calcium ATPase activity in colorectal cancer[J].Cell Biochem Biophys,2015,73(1):137-145.
[10]	QIN G,ZHAO C,ZHANG L,et al.Dihydroartemisinin induces apoptosis preferentially via a Bim-mediated intrinsic pathway in hepatocarcinoma cells[J].Apoptosis,2015,20(8):1072-1086.
[11]	LIAO K,LI J,WANG Z.Dihydroartemisinin inhibits cell proliferation via AKT/GSK3β/cyclinD1 pathway and induces apoptosis in A549 lung cancer cells[J].Int J Clin Exp Pathol,2014,7(12):8684.
[12]	FASANO E,SERINI S,PICCIONI E,et al.DHA induces apoptosis by altering the expression and cellular location of GRP78 in colon cancer cell lines[J].Biochim Biophys Acta,2012,1822(11):1762-1772.
[13]	CHEN S S,HU W,WANG Z,et al.p8 attenuates the apoptosis induced by dihydroartemisinin in cancer cells through promoting autophagy[J].Cancer Biol Ther,2015,16(5):770-779.
[14]	CHEN M,CHEN T S,LU Y Y,et al.Dihydroarteminsin-induced apoptosis is not dependent on the translocation of Bim to the endoplasmic reticulum in human lung adenocarcinoma cells[J].Pathol Oncol Res,2012,18(4):809-816.
[15]	ZHANG C,SYED T W,LIU R,et al.Role of endoplasmic reticulum stress,autophagy,and inflammation in cardiovascular disease[J].Front Cardiovasc Med,2017,4:29.
[16]	DU X X,LI Y J,WU C L,et al.Initiation of apoptosis,cell cycle arrest and autophagy of esophageal cancer cells by dihydroartemisinin[J].Biomed Pharmac,2013,67(5):417-424.
[17]	MARCINIAK S J,RON D.Endoplasmic reticulum stress signaling in disease[J].Physiol Rev,2006,86(4):1133-1149.
[18]	SCHRÖDER M.Endoplasmic reticulum stress responses[J].Cell Mol Life Sci,2008,65(6):862-894.
[19]	WANG M,KAUFMAN R J.Protein misfolding in the endoplasmic reticulum as a conduit to human disease[J].Nature,2016,529(7586):326-335.
[20]	HANAHAN D,WEINBERG R A.Hallmarks of cancer:the next generation[J].Cell,2011,144(5):646-674.
[21]	INGHAM M,SCHWARTZ G K.Biology of neoplasia:cell-cycle therapeutics come of age[J].J Clin Oncol,2017,35(25):2949-2959.
[22]	MAGENTA D,SANGIOVANNI E,BASILICO N,et al.Inhibition of metalloproteinase-9 secretion and gene expression by artemisinin derivatives[J].Acta Trop,2014,140:77-83.
[23]	LIN R,ZHANG Z,CHEN L,et al.Dihydroartemisinin (DHA) induces ferroptosis and causes cell cycle arrest in head and neck carcinoma cells[J].Cancer Lett,2016,381(1):165-175.
[24]	TONG Y,LIU Y,ZHENG H,et al.Artemisinin and its derivatives can significantly inhibit lung tumorigenesis and tumor metastasis through Wnt/β-catenin signaling[J].Oncotarget,2016,7(21):31413-31428.
[25]	MI Y,GENG G,ZOU Z,et al.Dihydroartemisinin inhibits glucose uptake and cooperates with glycolysis inhibitor to induce apoptosis in non-small cell lung carcinoma cells[J].PloS ONE,2015,10(3):e0120426.
[26]	ALASEEM A,ALHAZZANI K,Dondapati P,et al.Matrix metalloproteinases:a challenging paradigm of cancer management[J].Semin Cancer Biol,2017,Epub.
[27]	SHAO Y Y,ZHANG T L,WU L X,et al.AKT Axis,miR-21,and RECK play pivotal roles in dihydroartemisinin killing malignant glioma cells[J].Int J Mol Sci,2017,18(2):350.
[28]	HWANG Y P,YUN H J,KIM H G,et al.Suppression of PMA-induced tumor cell invasion by dihydroartemisinin via inhibition of PKCalpha/Raf/MAPKs and NF-kappaB/AP-1-dependent mechanisms[J].Biochem Pharmacol,2010,79(12):1714-1726.
[29]	HU C J,ZHOU L,CAI Y.Dihydroartemisinin induces apoptosis of cervical cancer cells via upregulation of RKIP and downregulation of bcl-2[J].Cancer Biol Ther,2014,15(3):279-288.
[30]	CHEN J,CHEN X,WANG F,et al.Dihydroartemisinin suppresses glioma proliferation and invasion via inhibition of the ADAM17 pathway[J].Neurol Sci,2015,36(3):435-440.
[31]	WANG S J,SUN B,CHENG Z X,et al.Dihydroartemisinin inhibits angiogenesis in pancreatic cancer by targeting the NF-κB pathway[J].Cancer Chemother Pharmacol,2011,68(6):1421.
[32]	PILATI P,NITTI D,MOCELLIN S.Cancer resistance to type Ⅱ topoisomerase inhibitors[J].Curr Med Chem,2012,19(23):3900-3906.
[33]	WIJDEVEN R H,PANG B,ASSARAF Y G,et al.Old drugs,novel ways out:Drug resistance toward cytotoxic chemotherapeutics[J].Drug Resist Updat,2016,28:65-81.
[34]	ONTIKATZE T,RUDNER J,HANDRICK R,et al.Dihydroartemisinin is a hypoxia-active anti-cancer drug in colorectal carcinoma cells[J].Front Oncol,2014,4:116.
[35]	CARO J T,MARíN L M,IAZBIK M C,et al.Markers of iron metabolism in retired racing greyhounds with and without osteosarcoma[J].Vet Clin Pathol,2013,42(3):360-363.
[36]	JIA L,SONG Q,ZHOU C,et al.Dihydroartemisinin as a putative STAT3 inhibitor,suppresses the growth of head and neck squamous cell carcinoma by targeting Jak2/STAT3 signaling[J].PloS ONE,2016,11(1):e0147157.
[37]	CAO L,DUANMU W,YIN Y,et al.Dihydroartemisinin exhibits anti-glioma stem cell activity through inhibiting p-AKT and activating caspase-3[J].Pharmazie,2014,69(10):752-758.

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Research progress on anti-tumor mechanisms of dihydroartemisinin

doi: 10.3969/j.issn.1006-0111.2019.03.003

Abstract

References

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通讯作者: 陈斌, bchen63@163.com

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