The effect of tamoxifen and fenretinimide on human colorectal cancer cell lines in vitro.
BACKGROUND
The natural history of colorectal neoplasia may be influenced by steroid hormones and nutritional compounds. We evaluated the effect of the anti-estrogenic tamoxifen (Tx), and the synthetic retinoid fenretinimide (4-HPR) on the growth of human colorectal cancer cells.


METHODS
DLD-1, CACO-2, SW-620, and COLO-205 colon cancer cells, and SW-1463 and SW-837 rectal cancer cells were cultured under serum-free conditions. Quadruplicates wells (4 x 10(4) cells/well) were created for each treated, and untreated groups in each cell line. Cells were treated with 1 microM Tx, 5 microM Tx, 1 microM 4-HPR, 1 microM Tx with 1 microM 4-HPR, and 5 microM Tx with microM 4-HPR. Cell growth was measured colorimetrically with the hexosaminidase assay (405 nm), and was compared among the different groups. Cells were analyzed for estrogen receptors using an enzyme immunoassay.


RESULTS
Tamoxifen, 4-HPR, or both, inhibited the growth in DLD-1 (P = .001), COLO-205 (P = .02), SW-620 (P = .001), and CACO-2 (P = .02) cell lines. Tamoxifen with 4-HPR inhibited cell growth more (P = .03) than did either Tx or 4-HPR in DLD-1, COLO-205, and SW620 cancer cells. Tamoxifen, 4-HPR, or both, had no effect on the growth of SW-837 (P = .14) cancer cells. Tamoxifen with 4-HPR promoted (P = .02) growth in SW-1463 cells, but not when added separately. Estrogen receptors were not found in any of the cells.


CONCLUSIONS
Under serum-free conditions, Tx, 4-HPR, or both, inhibit the growth of human colon cancer cells but not of rectal cancer cells. Combined treatment with Tx and 4-HPR is more effective than treatment with either of the agents alone in inhibiting of cell growth. The mechanism of inhibition is not clear yet, and further studies are warranted.
Department of Colorectal Surgery, Cleveland Clinic Foundation, OH 44195.
Y
Y
Ziv
M K
MK
Gupta
J W
JW
Milsom
A
A
Vladisavljevic
M
M
Brand
V W
VW
Fazio
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017313:Fenretinide / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D013629:Tamoxifen; D017313:Fenretinide