The isoprenoid derivative N⁶‐benzyladenosine CM223 exerts antitumor effects in glioma patient‐derived primary cells through the mevalonate pathway

Abstract

The biological effects together with structural data on interaction of CM223 with FPPS, provided additional evidence for the correlation of the i6A/CM223 antitumor activity with FPPS modulation. Because the MVA pathway is an important promising target, CM223 and its derivatives should be considered interesting active molecules in antiglioma research.

Identification of New Genetic Clusters in Glioblastoma Multiforme: EGFR Status and ADD3 Losses Influence Prognosis

“…Contrary to what was expected, it was shown that adenosine did not significantly accumulate in GB [55]. This fact would be in line with previous descriptions of N6-isopentenyladenosine and other modified nucleosides, with important anti-proliferative and pro-apoptotic effects in GB cases that display amplification on EGFR [56,57]. Interestingly, in our study, cluster 2 and 3 showed amplifications on EGFR and losses on CDKN2A in all cases, along with a high proportion of cases displaying MTAP losses.…”

Keratinocytes Migration Promotion, Proliferation Induction, and Free Radical Injury Prevention by 3-Hydroxytirosol

“…Cells were grown in p100 tissue culture plates at a density of 2 × 10 4 cells/cm 2 for 24 h. Cells were then incubated with HT, H 2 O 2 (for 6 h), or their combination (HT for 18 h and H 2 O 2 for an additional 6 h) at the indicated concentrations. Subsequently, cells were washed with PBS, harvested, and lysed in ice-cold radioimmunoprecipitation assay (RIPA) lysis buffer (50 mM Tris-HCl, 150 mM NaCl, 0.5% Triton X-100, 0.5% deoxycholic acid, 10 mg/mL leupeptin, 2 mM phenylmethylsulfonyl fluoride, and 10 mg/mL aprotinin) and then assayed for Western Blot (WB) by the procedure described in detail elsewhere [ 71 ].…”

Cholesterol Metabolism: A Potential Therapeutic Target in Glioblastoma

“…Recent work published by Ciaglia et al shows antitumor activity of N6-isopentenyladenosine (iPA) on glioma cells. Its mechanism of action is primarily driven through AMPK-dependent epidermal growth factor receptor (EGFR) degradation, which further adds value to its candidacy as a potent antitumor drug [93,94]. Thus, multiple preclinical studies demonstrate that targeting the cholesterol synthesis pathway could be useful for modulating cancer growth, either through directly inhibiting cholesterol synthesis, or though inhibiting the production of mevalonate pathway-derived moieties used in protein post-translational modifications of oncogenes.…”