(8R)-3β,8-Dihydroxypolypoda-13E,17E,21-triene Induces Cell Cycle Arrest and Apoptosis in Treatment-Resistant Prostate Cancer Cells

Abstract

Mastic, a resinous exudate from Pistacia lentiscus, has been reported to exhibit selective cytotoxicity against different cancer cell lines. There are, however, no data published correlating distinct mastic-derived compounds with the postulated cytotoxic activity. A polypodane-type bicyclic triterpenoid, (8R)-3β,8-dihydroxypolypoda-13E,17E,21-triene (1), was isolated from P. lentiscus oleogum resin. In androgen-independent PC-3 prostate cancer cells, 1 potently inhibited the expression of cyclins D1 and E, but had no effect on the expression of the cyclin kinase inhibitor p21(Waf1/Cip1). Inhibition of the expression of cell cycle-regulating cyclins resulted in cell cycle arrest in the G₀/G₁ phase, reduction in the number of cells in the S phase, and the triggering of apoptosis, as detected by increased expression of phosphatidylserine on the cell surface and by formation of DNA laddering. In addition, 1 suppressed the formation of prostate cancer colonies in soft agar and inhibited proliferation, angiogenesis, and the growth of prostate tumors xenografted onto chick chorioallantoic membranes without overt systemic toxicity. Taken together, these data show that 1 triggers apoptosis in chemoresistant, androgen-independent human prostate cancer cells in vitro and in vivo. Thus, 1 may serve as a lead compound for targeting so far incurable androgen-insensitive prostate cancers.

Tamoxifen magnifies therapeutic impact of ceramide in human colorectal cancer cells independent of p53

“…DNA content was measured according to published protocol [25] with modification. Cells were seeded in 6-cm dishes at 200,000 cells/dish in 10% FBS medium.…”

Inhibition of the Inflammasome NLRP3 by Arglabin Attenuates Inflammation, Protects Pancreatic -Cells from Apoptosis, and Prevents Type 2 Diabetes Mellitus Development in ApoE2Ki Mice on a Chronic High-Fat Diet

“…Arglabin (CAS 84692-91-1) (C 15 H 18 O 3 ), 3H-oxireno [8,8a]azuleno [4,5-b]furan-8(4aH)-one,5,6,6a,7,9a,9b-hexahydro-1,4a-dimethyl-7-methylene-(3aR,4aS,6aS,9aS,9bR), was purified to chemical homogeneity by reverse-phase high-performance liquid chromatography Morad et al, 2011). An Artemisia glabella raw extract was dissolved and applied onto a semipreparative Reprosil PUR ODS-3 column (Dr.Maisch GmbH, Ammerbuch-Entringen, Germany); it was subsequently eluted with methanol-water, and the fractions containing pure arglabin were detected by a photodiode array detector at 210 and 250 nm.…”

Anti-Inflammatory and Antiatherogenic Effects of the NLRP3 Inflammasome Inhibitor Arglabin in ApoE 2 .Ki Mice Fed a High-Fat Diet

“…Even today, plant-derived natural products and their derivatives and synthetic mimics make up a considerable portion of currently available drugs. 22 Neutraceutical aspects are based on their favorable properties as small molecules and the fact that they very often possess rather unusual structural features, which cannot be easily mimicked, not even by combinatorial chemistry. On the basis of these properties, such compounds may serve as lead compounds for the development of new drugs.…”