Description

Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties. Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC₅₀s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC₅₀ = >40 μM). It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1/2 by MEK1/2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC₅₀s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC₅₀s = >35 μM). It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G₀/G₁ phase, in both neuroblastoma and pancreatic cancer cells. Nemorosone (50 mg/kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.

Uses

Nemorosone is the main component of the floral resin of Clusia rosea. Nemorosone has an antiproliferative effect on cancer cells. Nemorosone induces apoptosis in HT-29 and LoVo cells[1][2].

in vivo

References

[1] Frión-Herrera Y, Gabbia D, Scaffidi M, et al. The Cuban Propolis Component Nemorosone Inhibits Proliferation and Metastatic Properties of Human Colorectal Cancer Cells. Int J Mol Sci. 2020;21(5):1827. Published 2020 Mar 6. DOI:10.3390/ijms21051827
[2] Wolf RJ, et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One. 2013;8(9):e74555. Published 2013 Sep 5. DOI:10.1371/journal.pone.0074555