Gene/Protein Disease Symptom Drug Enzyme Compound
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 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glycyrrhetinic acid (GA) is the active compound in Glycyrrhizae radix, a famous traditional Chinese medicine. Recently the anticancer activity of GA became the focus of scientific interest and many GA derivatives were developed as anti-tumor lead compounds. We previously reported that AEGA, a GA derivative, has proliferation inhibition and apoptosis-inducing activity in various human tumor cells. The present study was undertaken to further investigate the molecular mechanisms involved in AEGA-induced apoptosis in human leukemia K562 cells. AEGA can inhibit the growth of K562 cells in dose- and time-dependent manners determined by the MTT assay. Induction of apoptosis was evidenced by morphological changes and biochemical markers such as cell shrinkage, chromatin condensation and DNA ladder formation. Further mechanistic analysis revealed that AEGA induced apoptosis through the collapse of mitochondrial membrane potential, the accumulation of the cytosolic cytochrome c and the activation of caspase-9 and caspase-3. The apoptosis induction by AEGA was associated with the alteration in the ratio of Bcl-2/Bax protein expression. These results suggest that AEGA may induce apoptosis through a mitochondria-mediated pathway, and might have the therapeutic value against hematological malignancies.
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PMID:Induction of apoptosis with mitochondrial membrane depolarization by a glycyrrhetinic acid derivative in human leukemia K562 cells. 2369 31

Glycyrrhetinic acid has been usually studied for their anti-tumor activities. However, the low bioavailability and poor aqueous solubility as well as limited intracellular accumulation have limited their utility. In this present study, a series of new glycyrrhetinic acid conjugates with a triphenylphosphonium cation (TTP+) moiety, meant to specifically target them to tumor cells mitochondria, have been designed and synthesized. Among them, compound 2f possessed excellent antitumor activities against the tested human cancer cells, and simultaneously exhibited better cell selectivity between cancer cells and normal cells than glycyrrhetinic acid and HCPT. Moreover, 2f significantly induced cell cycle arrest at the G2/M phase, and effectively inhibited cancer cells proliferation and migration. Mechanism studies revealed that 2f triggered apoptosis through the mitochondrial pathway via the collapse of mitochondrial membrane potential, reactive oxygen species production and the activation of caspase-9 and caspase-3.
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PMID:Mitochondria-targeted triphenylphosphonium conjugated glycyrrhetinic acid derivatives as potent anticancer drugs. 3062 10