Effect of artemisinin derivatives on apoptosis and cell cycle in prostate cancer cells
- 1 April 2010
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Anti-Cancer Drugs
- Vol. 21 (4), 423-432
- https://doi.org/10.1097/cad.0b013e328336f57b
Abstract
Artemisinin is a plant-derived anti-malarial drug that has relatively low toxicity in humans and is activated by heme and/or intracellular iron leading to intracellular free radical formation. Interestingly, artemisinin has displayed anti-cancer activity, with artemisinin dimers being more potent than monomeric artemisinin. Intracellular iron uptake is regulated by the transferrin receptor (TfR), and the activity of artemisinin depends on the availability of iron. We examined the level of TfR in prostate cancer (PCa) tumor cells, synthesized two new artemisinin dimers, and evaluated the effect of dihydroartemisinin and artemisinin dimers, ON-2Py and 2Py, on proliferation and apoptosis in PCa cells. TfR was expressed in the majority of PCa bone and soft tissue metastases, all 24 LuCaP PCa xenografts, and PCa cell lines. After treatment with dihydroartemisinin, ON-2Py, or 2Py all PCa cell lines displayed dose-dependent decrease in cell number. 2Py was most effective in decreasing cell number. An increase in apoptotic events and growth arrest was observed in the C4-2 and LNCaP cell lines. Growth arrest was observed in PC-3 cells, but no significant change was observed in DU 145 cells. Treatment with 2Py resulted in a loss of the anti-apoptotic protein survivin in all four cell lines. 2Py treatment also decreased androgen receptor and prostate-specific antigen expression in C4-2 and LNCaP cells, with a concomitant loss of cell cycle regulatory proteins cyclin D1 and c-Myc. This study shows the potential use of artemisinin derivatives as therapeutic candidates for PCa and warrants the initiation of preclinical studies.Keywords
This publication has 34 references indexed in Scilit:
- Artemisinin dimer anticancer activity correlates with heme‐catalyzed reactive oxygen species generation and endoplasmic reticulum stress inductionInternational Journal of Cancer, 2009
- Artemisinin Blocks Prostate Cancer Growth and Cell Cycle Progression by Disrupting Sp1 Interactions with the Cyclin-dependent Kinase-4 (CDK4) Promoter and Inhibiting CDK4 Gene ExpressionJournal of Biological Chemistry, 2009
- β‐catenin mediates alteration in cell proliferation, motility and invasion of prostate cancer cells by differential expression of E‐cadherin and protein kinase D1Journal of Cellular Biochemistry, 2007
- Differential expression of angiogenesis associated genes in prostate cancer bone, liver and lymph node metastasesClinical & Experimental Metastasis, 2007
- Unopposed c-MYC expression in benign prostatic epithelium causes a cancer phenotypeThe Prostate, 2005
- Osteoprotegerin in Prostate Cancer Bone MetastasisCancer Research, 2005
- Survivin initiates procaspase 3/p21 complex formation as a result of interaction with Cdk4 to resist Fas-mediated cell deathOncogene, 2000
- Increased cell growth and tumorigenicity in human prostate LNCaP cells by overexpression to cyclin D1Oncogene, 1998
- Two Androgen Response Regions Cooperate in Steroid Hormone Regulated Activity of the Prostate-specific Antigen PromoterPublished by Elsevier BV ,1996
- D-type cyclinsTrends in Biochemical Sciences, 1995