Resveratrol inhibits cell growth in a human cholangiocarcinoma cell line.
OBJECTIVE
Cholangiocarcinoma is a devastating tumour with a poor prognosis. An efficient therapy is unavailable in unoperable patients and new drugs are widely sought for and required. Resveratrol (RES) is a natural molecule with a reported anticancer effect, evaluated on different tumour cell lines. We tested the efficacy of RES on a cholangiocarcinoma cell line for the first time.


METHODS
We used the human SK-ChA-1 cell line, cultured in the classical two-dimensional model and in the three-dimensional spheroids. After RES exposure morphology, cell viability (colony-forming assay), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and cancer antigen (CA) 19-9 medium releases, cellular transglutaminase activity, karyotype and cell cycle were evaluated.


RESULTS
Resveratrol inhibited cell growth in both the cell culture systems used (from -15 to -80% vs untreated controls) and induced a 40-fold increase of LDH and ALP activities in the culture medium. Also, transglutaminase (TG) activity increased in the cell lysates, together with a cell cycle perturbation characterised by an accumulation in the G(1)/S phase. Karyotype and CA 19-9 expression were not influenced by the treatment.


CONCLUSIONS
The observed cytotoxic effect of RES on the human cholangiocarcinoma SK-ChA-1 cell line cultured two- and three-dimensionally suggests to further analyse its chemotherapic/chemopreventive possibilities for this kind of cancer.
Roncoroni
Leda
L
Center for Prevention and Diagnosis of Celiac Disease, IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano, Italy.
Elli
Luca
L
Dolfini
Ersilia
E
Erba
Eugenio
E
Dogliotti
Elena
E
Terrani
Claudia
C
Doneda
Luisa
L
Grimoldi
Maria Grazia
MG
Bardella
Maria Teresa
MT
D000469:Alkaline Phosphatase / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000188:drug therapy*; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007621:Karyotyping; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D011503:Transglutaminases / Q000378:metabolism
D013267:Stilbenes; D007770:L-Lactate Dehydrogenase; D011503:Transglutaminases; D000469:Alkaline Phosphatase; D000077185:Resveratrol