RESUMO
Hepatocellular carcinoma (HCC) is most common in adults and has a high mortality rate because of a lack of effective treatment options. We investigated the effect of a medicinal plant as a potential source of drugs against HCC. The rhizomes of Dioscorea membranacea Pierre (DM), Hua-Khao-Yen in Thai, are commonly used as ingredients for alternative treatment of cancer in Thailand. In this study, the anticancer effects of DM extract in HCC-bearing rats were evaluated with respect to gross morphology, histopathology, and leakage of liver enzymes. In untreated HCCs, typical features of liver cancer, including hepatic nodules, thick-cell cords, and pseudoglandular cell arrangements, were observed. In addition, the HCCs showed abnormal reticulin patterns and a high glypican3 expression. In HCC-bearing rats treated with DM the cancer areas and reticulin expression were significantly reduced compared to the untreated group (p < 0.01). Sorafenib, the standard drug to treat HCC, reduced the cancer area further, but increased leakage of liver enzymes and decreased serum albumin concentration, indicating liver toxicity. These findings suggest that DM has an anticancer effect on HCCs in an animal model in vivo with potentially less severe side effects than sorafenib. Therefore, further studies of DM's mechanism of action in HCC should be carried out.
RESUMO
The herbal extract Benja-ummarit (BU) is a traditional Thai medicine with a putative cancer-suppressing effect. However, this effect has only been tested in vitro in human hepatocarcinoma cell lines. The present study determined the efficacy of a BU extract to treat hepatocellular carcinoma (HCC) in rats in vivo and established its anti-angiogenic and anti-proliferative properties. The BU extract was prepared in 95% ethanol and its composition determined using liquid chromatography-mass spectrometry. HCC was induced in Wistar rats by an injection of diethylnitrosamine (DEN), followed 2 weeks later by injections of thioacetamide (TAA) thrice weekly for 4 weeks. Following 2 months, the DEN-TAA-treated rats were divided into 6 groups that were treated orally for another 2 months with: i) No treatment; ii) vehicle; iii) 30 mg/kg sorafenib (SF); iv) 1 mg/kg BU; v) 10 mg/kg BU; or vi) 50 mg/kg BU. Liver samples were collected for gross morphological, histological, reverse transcription-quantitative PCR and western blot analyses, and serum samples were collected for liver function tests. The size and number of the cancer nodules were reduced ~10-fold in BU-treated HCC groups and ~14-fold in the SF-treated group compared with the HCC group. Furthermore, the serum parameters of liver damage were lower in BU-compared with SF-treated rats. These results indicate that while each of these formulations strongly reduce HCC expansion, BU extract results in less liver damage. Vascular endothelial growth factor expression was reduced significantly in the BU-and SF-treated HCC groups compared with the HCC group (P<0.05). BU extract antagonizes HCC growth in vivo potently through inhibiting tumor angiogenesis. BU, therefore, qualifies as a promising medical herb requiring further evaluation as a treatment of HCC.
RESUMO
Liver fibrosis is an excessive accumulation of scar tissue resulting from inflammation and cell death. Thioacetamide (TAA) is a well-known hepatotoxin that induces liver fibrosis. A marker of injured hepatocytes is transforming growth factor-beta 1 (TGF-ß1), while alpha-smooth muscle actin (α-SMA) and tissue inhibitor of metalloproteinase 1 (TIMP-1) are markers of activated hepatic stellate cells. Alpha-mangostin, a major xanthone derivative from the mangosteen pericarp, has been shown to have anti-oxidant and anti-inflammatory activities. The objective of this study was to determine whether alpha-mangostin has a protective effect on TAA-induced liver fibrosis in rats. The rats were treated by intraperitoneal injection of compounds for eight weeks. For the control group a mixture of dimethyl sulfoxide and phosphate buffered saline was administered. Two hundred mg/kg BW of TAA was administered three times weekly. Alpha-mangostin was administered at 5 mg/kg BW and silymarin at 100 mg/kg BW, both twice weekly. TAA induced histologically recognizable liver damage and fibrosis, as anticipated. Furthermore, it increased immunohistochemically detectable TGF-ß1, α-SMA and TIMP-1. Co-administration of alpha-mangostin or silymarin with TAA prevented or ameliorated the effects of TAA administration alone. The anti-fibrotic effect of alpha-mangostin was stronger than that of silymarin.
