in vitro
the substantial increase in saos-2-his-273-cells death could be noticed after being treated with 125 μm prima-1 for 48 hours. tunel staining revealed that such tumor-cell death was primarily triggered by apoptosis. prima-1 could also restore the transcriptional transactivation function to mutant p53 in vitro. [2]
in vivo
to assess the effect of prima-1 on human tumor xenografts, mice were inoculated with saos-2-his-273 cells expressing mutant p53. the mice then received prima-1 treatment at intra-tumor does of 20 mg/kg or i.v. doses of 20 and 100 mg/kg twice a day for three days. compared with the control group, the average tumor volume decreased from 555.7 mm3 to 11.7 (100 mg/kg) and 53 (20 mg/kg) mm3 after i.v. injections of prima-1. intra-tumor injections of prima-1 also decreased the average tumor volume to 5.3 mm3. [2]
References
[1] bykov v, issaeva n, zache n, shilov a, hultcrantz m, bergman j, selivanova g, wiman kg. reactivation of mutant p53 and induction of apoptosis in human tumor cells by maleimide analogs. j biol chem. 2005 aug; 280(34): 30384–91.
[2] bykov v, issaeva n, shilov a, hultcrantz m, pugacheva e, chumakov p, bergman j, wiman kg, selivanova g. restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound. nat med. 2002 mar; 8(3):282-8.
[3] lehmann s, bykov v, ali d, andren o, cherif h, tidefelt u, uggla b, yachnin j, juliusson g, moshfegh a, paul c, wiman kg, andersson po. targeting p53 in vivo: a first-in-human study with p53-targeting compound apr-246 in refractory hematologic malignancies and prostate cancer. j clin oncol. 2012. doi: 10.1200/jco.2011.40.7783.
