Molecular pharmacology and pharmacogenomics of artemisinin and its derivatives in cancer cells.
Secondary metabolites from plants can serve as defense against herbivores, microbes, viruses or competing plants. Many compounds from medicinal plants have pharmacological activities and thus may be a source for novel anti-tumor agents. We have analyzed natural products from traditional Chinese medicine during the past decade and focused our interest on the compound artemisinin from Artemisia annua L. (qinghao, sweet wormwood) and its derivatives. In addition to their anti-malarial properties, artemisinins are cytotoxic for cancer cells. The present review focuses on the mechanisms of action of artemisinins in cancer cells relating to: 1. anti-proliferative and anti-angiogenic effects, 2. induction of apoptosis, 3. oxidative stress, 4. oncogenes and tumor suppressor genes, and 5. multidrug resistance. Data on putative target molecules of artemisinins are presented and discussed, e.g. the translationally controlled tumor protein (TCTP). Emphasis is given to pharmacogenomic approaches to analyze the pleiotropic nature of mechanisms of artemisinins in cancer cells.
Efferth
Thomas
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German Cancer Research Center, M070, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. t.efferth@dkfz.de
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D037621:Artemisinins / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D016147:Genes, Tumor Suppressor / Q000187:drug effects; D005818:Genetic Engineering; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D018384:Oxidative Stress / Q000187:drug effects; D010597:Pharmacogenetics; D012717:Sesquiterpenes / Q000494:pharmacology*; D000090324:Tumor Protein, Translationally-Controlled 1
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D037621:Artemisinins; D012717:Sesquiterpenes; C000715647:TPT1 protein, human; D000090324:Tumor Protein, Translationally-Controlled 1; C031327:artemisinin