Combination therapy of a vitamin D3 analog and all-trans-retinoic acid: effect on human breast cancer in nude mice.
BACKGROUND
Vitamin D3 analogs and all-trans-retinoic acid (ATRA) are able to inhibit the growth of a variety of malignant cells.


METHODS
We examined the ability of three vitamin D3 analogs to inhibit the growth of a human mammary cancer cell line (MCF-7) in Beige Nude xid (BNX) mice either alone or with ATRA. Vitamin D3 analogs 1,25 dihydroxyvitamin D3 (code name, compound C), 1,25 (OH)2-16-ene-23-yne-19-nor-26,27-F6-D3 (compound LH) and 24a,26a,27a,-trihomo-22,24-diene-1,25(OH)2D3 (EB1089) were used.


RESULTS
The antitumor effect of ATRA alone was greater than that of either of the vitamin D3 analogs alone, and an additive effect was observed when a vitamin D3 analog and ATRA were administered together. EB1089 was the most potent vitamin D3 analog; and EB1089 plus ATRA was the most potent combination decreasing the tumor mass nearly 3-fold compared to tumors of diluent control mice. None of the animals became hypercalcemic. Their complete blood counts, serum electrolyte analysis as well as their liver and renal functions were all fairly similar and within the normal range.


CONCLUSIONS
This combination of a vitamin D3 analog and ATRA has the potential to be an adjuvant therapy for breast cancer.
Koshizuka
K
K
Division of Hematology/Oncology, UCLA School of Medicine, Cedars-Sinai Medical Center 90048, USA.
Kubota
T
T
Said
J
J
Koike
M
M
Binderup
L
L
Uskokovic
M
M
Koeffler
H P
HP
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002762:Cholecalciferol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D014212:Tretinoin / Q000008:administration & dosage*
D002762:Cholecalciferol; D014212:Tretinoin