P-0080 New Options in Hepatocellular Carcinoma Therapy: the Role of Quercetin and Cytochalasin-B

Abstract

IntroductionThe hepatocellular carcinoma (HCC) is the most frequent primary liver cancer. It has a reserved prognosis, therapeutically options are limited and it isn't always available. GLUT-1 is overexpressed in HCC and promotes tumorigenesis. Conversely, suppression of GLUT-1 by small interfering RNA (siRNA) significantly impaired growth and invasiveness of HCC cell lines, suggesting that GLUT-1 plays a direct role in oncogenesis, and not only to supply of glucose to meet energy requirements of cancer cells. Consequently it was proposed that GLUT-1 could be an innovative therapeutic target for HCC. Flavonoids and cytochalasin-B have shown potential as GLUT-1 function inhibition and they can be useful as therapeutic weapons against this highly aggressive kind of tumor. The aim of this study is to evaluate the potential anticancer effect on two cell lines of HCC differed on p53 expression, HePG2 (wp53) and HuH7 (mp53) of this compounds and their effect on 18F-FDG uptake. MethodsTwo different human HCC cell lines (HepG2 and HuH7) were used. In order to assess the different effects of quercetin, a flavonoid, and cytochalasin-B, these cells were cultivated in the presence of these compounds for different periods of time, and after cell proliferation was evaluated by the MTT test in order to calculate half maximal inhibitory concentration (IC50). To evaluate 18F-FDG uptake it was incubated in a cell suspension. Samples were collected and radioactivity was measured with a well-type gamma counter. ResultsIt was found that both compounds induced a decrease in cellular proliferation on both cell lines, and was shown that their effect depends on the time having cytochalasin-B more expressive results. Curiously, cytochalasin-B expressed better results in HuH7 cell-line, while quercetin had better result on HePG2 cell-line. Both compounds were able to decrease the percentage of 18F-FDG uptake in a similar way. ConclusionThese compounds have shown a promissory effect on HCC therapy. The decrease of cell proliferation could be associated with lower glucose uptake, as was shown with 18F-FDG. However, this effect seems that it depends on p53 expression. It suggests that therapies should be personalized according to genotype/phenotype of each tumor. Although this results, it needs more studies to clarify the role of p53 on HCC in these therapies.