Abstract
For the first time, we discovered a small proportion of aqueous fraction from Saw Palmetto apart from the fatty acid-rich fraction exhibited pharmacological activity. Therefore, this study aims to explore the anti-tumor potential of red pigmented aqueous fraction of Saw Palmetto, NYG on human hepatocellular carcinoma and its possible targets. Subcutaneous xenograft and orthotopic implantation models of HCC were used to evaluate the tumor inhibitory effect of NYG. Human hepatocellular carcinoma (HCC) cell lines and human umbilical vein endothelial cells (HUVEC) were used as in vitro model. The mRNA expression was conducted by qPCR. Protein expression was monitored by immunoblotting and immunohistochemistry. Cell migration and blood vessel formation were determined by chamber assay and tube formation assay, respectively. Significant tumor inhibition of NYG in dose-dependent manner was observed on subcutaneous xenograft and orthotopic HCC model. NYG has no direct action on cell viability or VEGF secretion of HCC cells. However, NYG reduced in vitro migration and vessel formation activities of HUVEC cells, as well as in vivo intratumoral neovascularization. NYG attenuated extracellular signal-regulated kinases (ERK) activation in endothelial cells, which may be associated with the suppression of migration and tube formation of HUVEC. NYG suppressed tumor expansion of HCC via inhibiting neovascularization, and may be potential adjuvant treatment for HCC.
Highlights
Liver cancer is one of the most prevalent human malignancies all over the world
Its aqueous fraction is rarely investigated, a previous study showed that the acidic water extract of Saw Palmetto exhibited anti-oxidant and COX-2 inhibitory effect [16]
This observation further supported another study on the inhibitory activity of Saw Palmetto berry extract on COX-2, which is associated with its prostate cancer cell growth suppression [17]
Summary
As the sixth most common cancer, there are 782,000 new cases of liver cancer diagnosed annually and the death rate is increasing annually [1]. Hepatocellular carcinoma (HCC) is the major form, accounting for 85% of liver cancer cases. As most HCC are highly radio- and chemo-resistant, desirable therapeutic outcome is hardly achieved in clinical cases with general cancer treatment protocols [4]. Therapeutic agents that and effectively target on HCC are always in need. Agents in blocking tumor neovascularization in HCC are available, and sorafenib was recently approved by FDA in targeting this process for HCC treatment [6]. Searching for an alternative medicine targeting on tumor neovascularization for treatment of HCC is still of interest
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