Incaspitolide A extracted fromCarpesium cernuuminduces apoptosisin vitrovia the PI3K/AKT pathway in benign prostatic hyperplasia

Abstract

Benign prostatic hyperplasia (BPH) is a common disease that occurs mainly in older men. The pathogenesis of BPH is complex and patients face a prolonged treatment course, and novel drugs with better selectivity and lower toxicity are required. incaspitolide A (compound TMJ-12) is a germacrane-type sesquiterpenoid compound extracted from the plant Carpesium carnuum. Extracts of C. carnuum are known to exert suppressive effects on BPH-1 cells. In this study, we investigated the molecular mechanisms underlying the suppressive effect of TMJ-12 specifically on BPH-1 cells. A cytotoxicity assay indicated that TMJ-12 inhibited BPH-1 cell proliferation, while flow cytometry assays showed that TMJ-12 induced G2/M phase cell cycle arrest and the apoptosis of BPH-1 cells. TMJ-12 was also shown to regulate the expression of several apoptosis- and cell cycle-related proteins, namely Bcl-2, Bax, Bad, Caspase-9, Caspase-3, CDK1, Cyclin B1, CDC25C, and c-Myc, among others. Collapse of the mitochondrial membrane potential (ΔΨm) following exposure to TMJ-12 was detected with the JC-1 staining assay. Further investigation revealed that treatment with TMJ-12 inhibited the PI3K/AKT pathway by increasing the expression of PTEN. Taken together, the results suggest that TMJ-12 prevents BPH-1 cell proliferation via the PI3K/AKT pathway by inducing apoptosis and cell cycle arrest.

The Flavagline Compound 1-(2-(dimethylamino)acetyl)-Rocaglaol Induces Apoptosis in K562 Cells by Regulating the PI3K/Akt/mTOR, JAK2/STAT3, and MAPK Pathways

“…The next day, the membranes were washed and incubated with the FITC-labeled secondary antibody at room temperature for 2 h. Finally, the membranes were scanned using the Odyssey Platform (LI-COR Biosciences, Lincoln, NE, USA). 24 …”

Chemical Composition and Cytotoxic Activity of Extracts from Carpesium divaricatum: In Vitro- versus Field-Grown Plants

“…are rich in sesquiterpene lactones and monoterpenoid thymol derivatives of well documented anti-inflammatory and cytotoxic activity [ 3 , 4 ]. Germacranolides isolated from the plants were frequently studied in respect of their cytotoxic activity against human cancer cells in vitro [ 5 , 6 , 7 , 8 ], but only a few studies dealt with the molecular mechanism of action of the compounds [ 9 , 10 , 11 ]. Recently, a paper reporting on poor selectivity of the cytotoxic effect exerted by Carpesium germacranolides has been published [ 12 ].…”