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.
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.
Authors: Lauren A Wise; Rose G Radin; Julie R Palmer; Shiriki K Kumanyika; Deborah A Boggs; Lynn Rosenberg Journal: Am J Clin Nutr Date: 2011-11-09 Impact factor: 7.045
Authors: Mary Ann Arndt; Valentina Battaglia; Eva Parisi; Mark J Lortie; Masato Isome; Christopher Baskerville; Donald P Pizzo; Riccardo Ientile; Sebastiano Colombatto; Antonio Toninello; Joseph Satriano Journal: Am J Physiol Cell Physiol Date: 2009-03-25 Impact factor: 4.249