Ponasterone A

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.

Ponasterone A具有高亲和力的蜕皮激素受体激动剂，属于植物蜕皮激素类化合物^[1-2]。Ponasterone A可作为细胞和转基因动物中基因表达的有效调节剂，实现报告基因的快速开启与关闭^[3-4]。

在体外，Ponasterone A（1–10μM）处理EcR293 clone-11 sub-1细胞3周，显著诱导iNOS表达，促进产生一氧化氮，Ponasterone A上调Fas和FasL mRNA表达^[5]。Ponasterone A（5–50μM）处理人Simpson‑Golabi‑Behmel综合征脂肪细胞，Ponasterone A未显著影响脂质积累或基础脂解作用，也未改变异丙肾上腺素刺激的脂解反应^[6]。

在体内，Ponasterone A（750μg）腹腔注射处理携带MMTV-VgEcR/RXRα和(E/GRE)3β-Gal三转基因的FVB小鼠（单次注射后24小时或皮下植入缓释颗粒持续10天），Ponasterone A可诱导乳腺上皮细胞中β-半乳糖苷酶基因的均匀且持续表达，且无显著组织毒性或乳腺发育异常^[7]。Ponasterone A（10mg/kg）每周两次腹腔注射处理，用于荷瘤（C8161 pVgRXR siGRM1 A13细胞）裸鼠（从肿瘤体积达10–20mm³开始，持续37–42天）。Ponasterone A显著抑制了肿瘤生长，增加了cleaved Caspase-3阳性细胞比例，下调了Ki-67阳性细胞比例^[8]。