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

This study examined the effects of the chemopreventive agents 4-(N-hydroxyphenyl)retinamide (4-HPR) and α-difluoromethylornithine (DFMO) on leiomyoma growth. Primary cultures of human uterine leiomyomas and matched normal myometrium were established from hysterectomy specimens. After treatment with...

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Bibliographic Details
Published in:American journal of obstetrics and gynecology 2004-03, Vol.190 (3), p.686-692
Main Authors: Broaddus, Russell R., Xie, Susu, Hsu, Ching-Ju, Wang, Jian, Zhang, Sui, Zou, Changping
Format: Article
Language:English
Subjects:
4-(N-hydroxyphenyl)retinamide
Antineoplastic Agents - pharmacology
Apoptosis
Biological and medical sciences
Cell Division - drug effects
Cyclin-Dependent Kinase Inhibitor p16 - metabolism
Cyclin-Dependent Kinase Inhibitor p21
Cyclins - metabolism
Eflornithine - pharmacology
Female
Female genital diseases
Fenretinide - pharmacology
Gynecology. Andrology. Obstetrics
Humans
Leiomyoma
Leiomyoma - pathology
Leiomyoma - physiopathology
Medical sciences
Tumor Cells, Cultured - drug effects
Tumor Suppressor Protein p53 - metabolism
Tumors
Uterine Neoplasms - pathology
Uterine Neoplasms - physiopathology
α-Difluoromethylornithine
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Summary:This study examined the effects of the chemopreventive agents 4-(N-hydroxyphenyl)retinamide (4-HPR) and α-difluoromethylornithine (DFMO) on leiomyoma growth. 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. 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. 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.
ISSN:0002-9378
1097-6868
DOI:10.1016/j.ajog.2003.09.048