licochalcone-a and Prostatic-Neoplasms

Licorice is a common Chinese medicinal herb with antitumor activity. Some components in licorice root have been shown to induce cell cycle arrest or apoptosis in cancer cells. This paper demonstrates for the first time that licorice Glycyrrhiza glabra and its component licochalcone-A (LA) can induce autophagy in addition to apoptosis in human LNCaP prostate cancer cells. Exposure of cells to licorice or LA resulted in several confirmed characteristics of autophagy, including the appearance of autophagic vacuoles revealed by monodansylcadaverine (MDC) staining, formation of acidic vesicular organelles (AVOs), and autophagosome membrane association of microtubule-associated protein 1 light chain 3 (LC3) characterized by cleavage of LC3 and its punctuate redistribution, as well as ultrastructural observation of autophagic vacuoles by transmission electron microscopy. Autophagy induction was accompanied by down-regulation of Bcl-2 and inhibition of the mammalian target of rapamycin (mTOR) pathway. In summary, licorice can induce caspase-dependent and autophagy-related cell death in LNCaP cells.

Topics: Autophagy; Cell Line, Tumor; Chalcones; Gene Expression; Genes, bcl-2; Glycyrrhiza; Humans; Male; Microscopy, Electron, Transmission; Prostatic Neoplasms; Protein Kinases; TOR Serine-Threonine Kinases; Vacuoles

Licochalcone (LA) is a novel estrogenic flavonoid isolated from PC-SPES composition herb licorice root that was reported to show significant antitumor activity in various malignant human cell lines. To better understand its anti-CaP activities, we have investigated LA-elicited growth control and induction of apoptosis using androgen-independent p53-null PC-3 prostate cancer cells. LA induced modest level of apoptosis but had more pronounced effect on cell cycle progression arresting cells in G2/M, accompanied by suppression of cyclin B1 and cdc2. It also inhibited phosphorylation of Rb, specifically phosphorylation of S780 with no change of phosphorylation status of T821, decreased expression of transcription factor E2F concurrent with reduction of cyclin D1, down-regulation of CDKs 4 and 6, but increased cyclin E expression. These findings provide mechanistic explanation for LA activity and suggest that it may be considered as a chemopreventive agent and its anticancer properties should be further explored.

Topics: Androgens; Antineoplastic Agents; Apoptosis; Cell Division; Cell Line, Tumor; Cell Size; Chalcone; Chalcones; Flavonoids; G1 Phase; G2 Phase; Glycyrrhiza; Humans; Male; Neoplasm Proteins; Plant Roots; Prostatic Neoplasms