Ponasterone A is a high-affinity ecdysone receptor agonist, belonging to the plant ecdysteroid class of compounds[1-2]. Ponasterone A can serve as an effective modulator of gene expression in cells and transgenic animals, enabling rapid switching on and off of reporter genes[3-4].
In vitro, EcR293 clone-11 sub-1 cells were treated with Ponasterone A (1–10μM) for 3 weeks. Ponasterone A significantly induced iNOS expression, promoted the production of nitric oxide, and upregulated the mRNA expression of Fas and FasL[5]. Human Simpson‑Golabi‑Behmel syndrome adipocytes treated with Ponasterone A (5–50μM), Ponasterone A did not significantly affect lipid accumulation or basal lipolysis, nor did Ponasterone A alter isoproterenol-stimulated lipolysis[6].
In vivo, FVB mice carrying the MMTV-VgEcR/RXRα and (E/GRE)3β-Gal triple transgene were intraperitoneally injected with Ponasterone A (750μg) (either 24 hours after a single injection or via subcutaneous implantation of sustained-release pellets for 10 days). Ponasterone A induced uniform and sustained expression of the β-galactosidase gene in mammary epithelial cells, with no significant tissue toxicity or abnormal mammary development[7]. Tumor-bearing nude mice (with C8161 pVgRXR siGRM1 A13 cells) were treated intraperitoneally with Ponasterone A (10mg/kg) twice weekly (starting when tumor volume reached 10–20mm³, lasting 37–42 days). Ponasterone A significantly inhibited tumor growth, increased the proportion of cleaved Caspase-3-positive cells, and decreased the proportion of Ki-67-positive cells[8].
References:
[1] Hansen KØ, Isaksson J, Glomsaker E, et al. Ecdysteroids from the Arctic Bryozoan Alcyonidium gelatinosum. Molecules. 2018 Jun 19;23(6):1481.
[2] Gu Y, Ihara Y. Evidence that collapsin response mediator protein-2 is involved in the dynamics of microtubules. J Biol Chem. 2000 Jun 16;275(24):17917-20.
[3] Xiao YY, Beilstein MA, Wang MC, et al. Development of a ponasterone A-inducible gene expression system for application in cultured skeletal muscle cells. Int J Biochem Cell Biol. 2003 Jan;35(1):79-85.
[4] McCarthy JF. Ponasterone A: a new ecdysteroid from the embryos and serum of brachyuran crustaceans. Steroids. 1979 Dec;34(7):799-806.
[5] Xu W, Liu L, Charles IG. Microencapsulated iNOS-expressing cells cause tumor suppression in mice. FASEB J. 2002 Feb;16(2):213-5.
[6] Todorova V, Savova MS, Ivanova S, et al. Anti-Adipogenic Activity of Rhaponticum carthamoides and Its Secondary Metabolites. Nutrients. 2023 Jul 7;15(13):3061.
[7] Albanese C, Reutens AT, Bouzahzah B, et al. Sustained mammary gland-directed, ponasterone A-inducible expression in transgenic mice. FASEB J. 2000 May;14(7):877-84.
[8] Wangari-Talbot J, Wall BA, Goydos JS, et al. Functional effects of GRM1 suppression in human melanoma cells. Mol Cancer Res. 2012 Nov;10(11):1440-50.