The aim of this study was to assess the efficiency of p53 reactivation and induction of massive apoptosis (PRIMA-1(Met)) in inducing myeloma cell death, using 27 human myeloma cell lines (HMCLs) and 23 primary samples. Measuring the lethal dose (LD50) of HMCLs revealed that HMCLs displayed heterogeneous sensitivity, with an LD50 ranging from 4 μM to more than 200 μM. The sensitivity of HMCLs di...

The transcriptional regulation of proline-rich membrane anchor (PRiMA), an anchoring protein of tetrameric globular form acetylcholinesterase (G(4) AChE), was revealed in muscle during myogenic differentiation under the influence of innervation. During myotube formation of C2C12 cells, the expression of AChE(T) protein and the enzymatic activity were dramatically increased, but the level of G(4...

Targeting p53 by the small-molecule PRIMA-1/APR-246 has shown promising preclinical activity in various cancer types. However, the mechanism of PRIMA-1–induced apoptosis is not completely understood and its effect on multiple myeloma cells is unknown. In this study, we evaluated antitumor effect of PRIMA-1 alone or its combination with current antimyeloma agents in multiple myeloma cell lines, ...

Targeting p53 by the small-molecule PRIMA-1(Met)/APR-246 has shown promising preclinical activity in various cancer types. However, the mechanism of PRIMA-1(Met)-induced apoptosis is not completely understood and its effect on multiple myeloma cells is unknown. In this study, we evaluated antitumor effect of PRIMA-1(Met) alone or its combination with current antimyeloma agents in multiple myelo...

Reactivation of the tumor suppressor activity to mutant p53 should trigger massive apoptosis and eliminate tumors. The low molecular weight compounds PRIMA-1 and the structural analog PRIMA-1MET reactivate human mutant p53 in vitro and suppress growth of human tumor xenografts in SCID mice. However, little is known about their effect on mouse mutant p53 in mouse tumor cells. We have examined th...

Acetylcholinesterase (AChE) accumulates on axonal varicosities and is primarily found as tetramers associated with a proline-rich membrane anchor (PRiMA). PRiMA is a small transmembrane protein that efficiently transforms secreted AChE to an enzyme anchored on the outer cell surface. Surprisingly, in the striatum of the PRiMA knock-out mouse, despite a normal level of AChE mRNA, we find only 2-...

BACKGROUND Since ovarian cancer is associated with high frequency of p53 mutation, the availability of p53 reactivation and induction of massive apoptosis (PRIMA-1) offers a possible new therapeutic strategy for overcoming this devastating disease. Although Akt activation is believed to be a determinant in chemoresistance in ovarian cancer, whether Akt plays a role in regulating the effectivene...

We recently identified PRIMA-1 as a low molecular weight compound that restores tumor suppressor function to mutant p53 proteins and has anti-tumor activity in vivo (1). Here we report the statistical analysis of the effect of PRIMA-1 on a panel of human tumor cell lines using information available in a database at the Developmental Therapeutics Program of the National Cancer Institute (NCI). W...

BACKGROUND/AIM Derivatives of PRIMA-1 compound, 8a and 8b have been shown to increase cytotoxicity in lung cancer cells through sphingomyelinase pathways in IR and 8a or 8b co-treated lung cancer cells. The goal of the present study was to further elaborate the molecular mechanism of 8a- or 8b-treated lung cancer cells in order to understand their potential as anti-cancer drugs. MATERIALS AND...

p53 Reactivation and induction of massive apoptosis (PRIMA-1) is a small-molecule compound that reactivates mutant p53, restoring its normal tumor suppressor function. PRIMA-1 effectively suppresses the growth of homogeneous p53-deficient tumor xenografts in immunosuppressed mice; however, the ability of PRIMA-1 to suppress the growth of mammary tumors in rodents and other species is not well c...