Cell Cycle

Publication Title: 
Molecular Pharmacology

A profound cytotoxic action of the antimalarial, artesunate (ART), was identified against 55 cancer cell lines of the U.S. National Cancer Institute (NCI). The 50% inhibition concentrations (IC50 values) for ART correlated significantly to the cell doubling times (P = 0.00132) and the portion of cells in the G0/G1 (P = 0.02244) or S cell cycle phases (P = 0.03567). We selected mRNA expression data of 465 genes obtained by microarray hybridization from the NCI data base.

Author(s): 
Efferth, Thomas
Sauerbrey, Axel
Olbrich, Armin
Gebhart, Erich
Rauch, Pia
Weber, H. Oliver
Hengstler, Jan G.
Halatsch, Marc-Eric
Volm, Manfred
Tew, Kenneth D.
Ross, Douglas D.
Funk, Jens Oliver
Publication Title: 
Anticancer Research

Artemisinin (AR) is a widely used antimalarial drug. Recently, additional uses for AR as an anticancer drug were discovered. Using TUNEL, immunohistochemistry (IHS) markers and flow cytometry techniques, we evaluated the effect of AR and 5-FU on HPV 16 immortalized and transformed human gingival epithelial (IHGK) cells. The results of TUNEL showed that AR-treated IHGK cells consisted of 82% positive cells, while 5-FU-treated cells consisted of 18% positive cells.

Author(s): 
Yamachika, Eiki
Habte, Temesgen
Oda, Dolphine
Publication Title: 
Biomedical Research (Tokyo, Japan)

Chloroquine, quinine, artemisinin, and pyrimethamine are generally considered safe drugs for treatment of malaria during pregnancy; however, high doses of these drugs are detrimental with adverse outcome of pregnancy. Since antimalarial drugs interaction with placental cells has not been addressed, in this study, we employed a non-radioactive proliferation assay and lactate dehydrogenase (LDH) release assays to investigate the effect of these drugs on JAR trophoblastic cell survival.

Author(s): 
Nilkaeo, Athip
Bhuvanath, Suthinee
Praputbut, Sakonwun
Wisessombat, Seuptrakool
Publication Title: 
British Journal of Pharmacology

BACKGROUND AND PURPOSE: Artemisinin and its derivatives exhibit potent immunosuppressive activity. The purpose of the current study was to examine the immunosuppressive activity of artemether directly on T lymphocytes and to explore its potential mode of action. EXPERIMENTAL APPROACH: In vitro, T-cell proliferation was measured using [(3)H]-thymidine incorporation assay in cells stimulated with ConA, alloantigen and anti-CD3 antibody. CFSE-labeled cell division and cell cycle distribution were monitored by flow cytometry.

Author(s): 
Wang, J.-X.
Tang, W.
Shi, L.-P.
Wan, J.
Zhou, R.
Ni, J.
Fu, Y.-F.
Yang, Y.-F.
Li, Y.
Zuo, J.-P.
Publication Title: 
Acta Pharmacologica Sinica

AIM: To investigate the anticancer activity of dihydroartemisinin (DHA), a derivative of antimalaria drug artemisinin in a panel of human ovarian cancer cell lines. METHODS: Cell growth was determined by the MTT viability assay. Apoptosis and cell cycle progression were evaluated by a DNA fragmentation gel electro-phoresis, flow cytometry assay, and TUNEL assay; protein and mRNA expression were analyzed by Western blotting and RT-PCR assay.

Author(s): 
Jiao, Yang
Ge, Chun-Min
Meng, Qing-Hui
Cao, Jian-ping
Tong, Jian
Fan, Sai-Jun
Publication Title: 
Zhong Xi Yi Jie He Xue Bao = Journal of Chinese Integrative Medicine

OBJECTIVE: To explore the effect of artesunate (ART) on cell differentiation and cell cycle distribution of the prostate cancer cell line PC-3 in vitro. METHODS: PC-3 cells were cultivated with ART from logarithmic growth phase. After 48-hour treatment, the cell cycles were detected by flow cytometry (FCM), and enzyme linked immunosorbent assay was used to detect the level of prostate specific antigen (PSA) in cell culture supernatant. The change of cellular morphology was observed under a transmission electron microscope (TEM).

Author(s): 
Huang, Xiao-fei
Yuan, Ding
Zhang, Chang-cheng
Zhang, Xiao-peng
Publication Title: 
Clinical Cancer Research: An Official Journal of the American Association for Cancer Research

PURPOSE: ART and its derivatives, clinically used antimalarial agents, have recently shown antitumor activities. However, the mechanisms underlying these activities remain unclear. This study was designed to determine their antitumor efficacy and underlying mechanisms of action in human hepatoma cells. EXPERIMENTAL DESIGN: The in vitro cytotoxicities of ART, DHA, artemether, and artesunate were compared in human hepatoma cells, HepG2 (p53 wild-type), Huh-7 and BEL-7404 (p53 mutant), and Hep3B (p53 null), and a normal human liver cell line, 7702.

Author(s): 
Hou, Junmei
Wang, Disong
Zhang, Ruiwen
Wang, Hui
Publication Title: 
The Journal of Biological Chemistry

Artemisinin, a naturally occurring component of Artemisia annua, or sweet wormwood, is a potent anti-malaria compound that has recently been shown to have anti-proliferative effects on a number of human cancer cell types, although little is know about the molecular mechanisms of this response. We have observed that artemisinin treatment triggers a stringent G1 cell cycle arrest of LNCaP (lymph node carcinoma of the prostate) human prostate cancer cells that is accompanied by a rapid down-regulation of CDK2 and CDK4 protein and transcript levels.

Author(s): 
Willoughby, Jamin A.
Sundar, Shyam N.
Cheung, Mark
Tin, Antony S.
Modiano, Jaime
Firestone, Gary L.
Publication Title: 
International Journal of Cancer. Journal International Du Cancer

Analogs of the malaria therapeutic, artemisinin, possess in vitro and in vivo anticancer activity. In this study, two dimeric artemisinins (NSC724910 and 735847) were studied to determine their mechanism of action. Dimers were >1,000 fold more active than monomer and treatment was associated with increased reactive oxygen species (ROS) and apoptosis induction. Dimer activity was inhibited by the antioxidant L-NAC, the iron chelator desferroxamine and exogenous hemin.

Author(s): 
Stockwin, Luke H.
Han, Bingnan
Yu, Sherry X.
Hollingshead, Melinda G.
Elsohly, Mahmoud A.
Gul, Waseem
Slade, Desmond
Galal, Ahmed M.
Newton, Dianne L.
Bumke, Maja A.
Publication Title: 
Anti-Cancer Drugs

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.

Author(s): 
Morrissey, Colm
Gallis, Byron
Solazzi, Jeffrey W.
Kim, Byung Ju
Gulati, Roman
Vakar-Lopez, Funda
Goodlett, David R.
Vessella, Robert L.
Sasaki, Tomikazu

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