Inhibitory effects of N-(4-hydrophenyl) retinamide on liver cancer and malignant melanoma cells.
OBJECTIVE
To investigate the effect of N-(4-hydrophenyl) retinamide (4-HPR), the derivative of retinoic acid, on inhibition of migration, invasion, cell growth, and induction of apoptosis in hepatocellular carcinoma cells (HCCs) and malignant melanoma cells.


METHODS
4-HPR was chemically synthesized. Cellular migration and invasion were assayed by Borden chamber experiment. Cell growth was assayed by MTT chromometry. Apoptosis effect was measured using Hoechst 32258 staining and flow cytometry. Gene transfection was performed with lipofectamine.


RESULTS
We observed that the migration of HCC and melanoma cells was significantly suppressed by 4-HPR and the migration cells were reduced to 58+/-5.03 (control 201+/-27.2, P<0.05, n = 4) in SMMC 7721-k3 HCC, and to 254+/-25.04 (control 302+/-30.1, P<0.05, n = 4) in melanoma cells after 6-h incubation with 4-HPR. The invasion through reconstituted basement membrane was also significantly reduced by 4-HPR treatment to 11.2+/-3.3 in SMMC 7721-k3 HCC (control 27+/-13.1), and to 24.3+/-3.2 in melanoma cells (control 67.5+/-10.1, P<0.05, n = 3). Cell growth, especially in melanoma cells, was also significantly inhibited. Furthermore, 3 micromol/L of 4-HPR induced apoptosis in B16 melanoma cells (37.11+/-0.94%) more significantly than all-trans retinoic acid (P<0.05), but it failed to induce apoptosis in SMMC 7721-k3 HCC. The mechanism for 4-HPR-induced apoptosis was not clear, but we observed that 4-HPR could regulate p27(kip1), and overexpression of cerebroside sulfotransferase (CST) diminished the apoptosis induced by 4-HPR in melanoma cells.


CONCLUSIONS
4-HPR is a potent inhibitor of HCC migration and inducer of melanoma cell apoptosis. CST and p27(kip1) expression might be associated with 4-HPR-induced apoptosis.
Wu
Xing-Zhong
XZ
Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China. xz_wu@shmu.edu.cn
Zhang
Li
L
Shi
Bi-Zhi
BZ
Hu
Ping
P
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D017313:Fenretinide / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D017313:Fenretinide; D015238:Sulfotransferases; C020556:galactosylceramide sulfotransferase