Crithmum maritimum restores the lipid and metabolic profiles of liver cancer cells to a normal phenotype

Abstract

Abstract Hepatocellular carcinoma (HCC) is becoming an alarming epidemiological clinical problem worldwide. Pharmacological approaches currently available do not provide adequate responses due to poor effectiveness, high toxicity, and serious side effects. We previously demonstrated that the wild edible plant Crithmum maritimum effectively slows the growth of liver cancer cells in vitro by reducing the bioenergetic and metabolic characteristics typical of transformed cells, particularly the fermentative phenotype (Warburg effect). Moreover, we found that Crithmum maritimum improves the expression of markers of differentiated hepatocytes. Here, we aimed to further characterize the effects of Crithmum maritimum on lipid accumulation and metabolism in HCC cells with different degrees of transformation. Additionally, we wanted to study markers of cellular metabolic health, such as AMP-activated protein kinase (AMPK), Sirtuin 1 (SIRT1), and Sirtuin 3 (SIRT3), as well as the insulin signaling pathway. To better model the biological spectrum of HCC, we employed HCC cell lines with varying degrees of transformation and invasiveness. Results indicate that Crithmum maritimum prevents lipid accumulation, downregulates lipid and cholesterol biosynthesis, and modulates markers of metabolic health, such as AMPK, SIRT1 and SIRT3. This effect is differentially modulated in different HCC cell lines, revealing an important functional versatility of Crithmum maritimum. These findings confirm the importance of Crithmum maritimum as a valuable nutraceutical, reinforcing its role in improving metabolic health.