The chemopreventive agents 4-HPR and DFMO inhibit growth and induce apoptosis in uterine leiomyomas.

Abstract:

OBJECTIVE:This study examined the effects of the chemopreventive agents 4-(N-hydroxyphenyl)retinamide (4-HPR) and alpha-difluoromethylornithine (DFMO) on leiomyoma growth. STUDY DESIGN:Primary cultures of human uterine leiomyomas and matched normal myometrium were established from hysterectomy specimens. After treatment with 4-HPR, DFMO, or the combination 4-HPR plus DFMO, cell growth was analyzed. Apoptosis was quantified with the use of a flow cytometric terminal deoxynucleotidyl transferase-mediated fluorescein-deoxyuridine-triphosphate nick-end labeling assay. Protein extracts were analyzed with Western blot for p53, p21, and p16. RESULTS:4-HPR and DFMO inhibited the growth and induced apoptosis of leiomyoma cells, but not matched normal myometrial cells. Both 4-HPR and DFMO caused cells to accumulate at G0/G1, with a corresponding decrease in the S-phase fraction. Both agents also caused the induction of p53, p21, and p16. CONCLUSION:The chemopreventive agents 4-HPR and DFMO inhibit leiomyoma cell growth in vitro and induce apoptosis, which implies that retinoids and polyamines are important regulators of leiomyoma growth.

journal_name

Am J Obstet Gynecol

authors

Broaddus RR,Xie S,Hsu CJ,Wang J,Zhang S,Zou C

doi

10.1016/j.ajog.2003.09.048

subject

Has Abstract

pub_date

2004-03-01 00:00:00

pages

686-92

issue

3

eissn

0002-9378

issn

1097-6868

pii

S0002937803017526

journal_volume

190

pub_type

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