Novel 20-epi-vitamin D3 analog combined with 9-cis-retinoic acid markedly inhibits colony growth of prostate cancer cells
✍ Scribed by Elstner, Elena; Campbell, Moray J.; Munker, Reinhold; Shintaku, Peter; Binderup, Lise; Heber, David; Said, Jonathan; Koeffler, H. Phillip
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 301 KB
- Volume
- 40
- Category
- Article
- ISSN
- 0270-4137
No coin nor oath required. For personal study only.
✦ Synopsis
BACKGROUND. 1,25 dihydroxyvitamin D 3 (1,25D) and retinoids may play an important role in preventing progression of prostate cancer. METHODS. We examined the ability of four novel 20-epi-vitamin D 3 analogs (CB1093, KH1060, KH1266, and CB1267), either alone or in combination with 9-cis retinoic acid (RA) to inhibit colony growth of a human prostate cancer cell line, LNCaP, using soft agar as well as bone marrow stroma. Also, the effect of these analogs on the cell cycle and expression of Ki-67, p21 waf-1 , and p27 kip1 in LNCaP cells was examined. RESULTS. The analog CB1267 was the most potent, with 8 × 10 -10 M of the analog inhibiting 50% colony growth (ED50) of LNCaP. 9-cis-RA also inhibited colony growth of LNCaP (ED50, 5 × 10 -7 M). Combined, CB1267 and 9-cis-RA synergistically inhibited colony growth and significantly increased the number of LNCaP cells in G0/G1 phase. Cell cycle arrest was associated with increased levels of p21 waf-1 and p27 kip1 and decreased expression of Ki-67 protein. Pulse-exposure to this combination (5 × 10 -8 M) irreversibly inhibited colony growth, both in soft agar and on normal human bone marrow stroma.