Abstract
BACKGROUND. Exposure of prostate carcinoma cells lines to retinoids, which function through the classical retinoic acid nuclear receptor, (RARs) or retinoid X receptors (RXRs), results in minimal cytostatic inhibition of cell proliferation. METHODS. Growth inhibition and various regulatory responses were investigated in two human prostate carcinoma cells lines (LNCaP and PC-3) treated with or without a synthetic retinoid, CD 437. RESULTS. Incubation of prostate carcinoma cell lines with a novel retinoid CD437 resulted in the marked inhibition of proliferation. LNCaP and PC-3 possessed IC50 values for CD437 of 375 nM and 550 nM, respectively. Incubation with 1 μM CD437 for 24 hr resulted in 100% and 60% inhibition of growth in LNCaP and PC-3 cells, respectively. Simultaneously, cell flow cytometric analyses revealed a dramatic increase of the cell population in S phase, in both LNCaP (from 38.6% up to 86.7%) and PC-3 (27.9% to 55.7%), and a decreased proportion of cells in G2 phase, in LNCaP (from 23.7% down to 1.2%) and PC-3 (14.9% to 2.2%), indicating a significant S-phase arrest. The cells growth inhibition and S-phase arrest in these cells were followed by apoptosis, as revealed by the acquisition of the characteristic cell morphology including the appearance of apoptotic bodies, and further confirmed by cellular DNA fragmentation. CD437-induced-S phase arrest was associated with upregulated mRNA levels of p21(waf1/cip1/sdi1) in both LNCaP (p53+/+) and PC-3 (53-/-) cells. CONCLUSIONS. CD437 represented a unique retinoid that induce S-phase arrest and apoptosis in both androgen-dependent (LNCaP) and -independent (PC-3) human prostate cancer cells, suggesting a potential role of CD437 in the treatment of human prostate cancer.
Original language | English (US) |
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Pages (from-to) | 228-236 |
Number of pages | 9 |
Journal | Prostate |
Volume | 38 |
Issue number | 3 |
DOIs | |
State | Published - Feb 15 1999 |
Externally published | Yes |
Keywords
- Apoptosis
- CD437
- Cell cycle
- Growth inhibition
- Retinoid
- p21(waf1/cip1/sdi1)
ASJC Scopus subject areas
- Oncology
- Urology