Evaluation of the medicinal herb Graptopetalum paraguayense as a treatment for liver cancer
Journal
PLoS ONE
Journal Volume
10
Journal Issue
4
Pages
e121298
Date Issued
2015
Author(s)
Hsu, W.-H.; Huang, K.-W.; Chen, Y.-C.; Hsu, S.-L.; Wu, L.-C.; Tsou, A.-P.; Lai, J.-M.; Huang, C.-Y.F.
Chen Y.-C.
Hsu S.-L.
Wu L.-C.
Tsou A.-P.
Lai J.-M.
Huang C.-Y.F.
Abstract
Background Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third most common cause of cancer-related death worldwide. Sorafenib is the only drug for patients with advanced-stage hepatocellular carcinoma (HCC) that has been shown to confer a survival benefit to patients with HCC; however, it has many side effects. Thus, alternate therapeutic strategies with improved safety and therapeutic efficacy for the management of HCC should be developed. Methods and Findings We demonstrate that an extract of Graptopetalum paraguayense (GP) down-regulated the expression levels of several onco-proteins, including AURKA, AURKB, and FLJ10540, in HCC cells. To isolate the active components in the GP extracts, we prepared extracts fractions and assessed their effects on the expression of onco-proteins in HCC cells. The fraction designated HH-F3 was enriched in active ingredients, exhibited cytotoxic effects, and suppressed the expression of the onco-proteins in HCC cells. The structure of the main active compound in HH-F3 was found to be similar to that of the proanthocyanidin compounds derived from Rhodiola rosea. In addition, a distinct new compound rich in 3, 4, 5-trihydroxy benzylic moieties was identified in the HH-F3 preparations. Mechanistic studies indicated that HH-F3 induced apoptosis in HCC cells by promoting the loss of mitochondrial membrane potential and the production of reactive oxygen species. HH-F3 also enhanced PTEN expression and decreased AKT phosphorylation at Ser473 in a concentration-dependent manner in HCC cells. Moreover combination of GP or HH-F3 and sorafenib synergistically inhibits the proliferation of Huh7 cells. The treatment of a rat model with diethylnitrosamine(DEN)-induced liver cancer with extracts of GP and HH-F3 decreased hepatic collagen contents and inhibited tumor growth. Conclusions These results indicate that GP extracts and HH-F3 can protect the liver by suppressing tumor growth; consequently, these compounds could be considered for the treatment of HCC. ? 2015 Hsu et al.
SDGs
Other Subjects
antineoplastic agent; aurora A kinase; aurora B kinase; diethylnitrosamine; FLJ10540 protein; Graptopetalum paraguayense extract; hydroxyproline; oncoprotein; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; plant extract; proanthocyanidin derivative; protein kinase B; reactive oxygen metabolite; sorafenib; unclassified drug; plant extract; reactive oxygen metabolite; tumor protein; animal experiment; animal model; animal tissue; antiproliferative activity; apoptosis; Article; bile flow; cancer inhibition; cell viability; chemical composition; concentration response; controlled study; down regulation; drug cytotoxicity; drug dose comparison; drug megadose; drug potentiation; Graptopetalum paraguayense; herb; human; human cell; liver cancer; liver cancer cell line; liver cirrhosis; liver fibrosis; low drug dose; male; mitochondrial membrane potential; nonhuman; protein expression; protein phosphorylation; rat; Rhodiola rosea; stellate cell; animal; biosynthesis; Carcinoma, Hepatocellular; chemistry; drug effects; evaluation study; gene expression regulation; Liver Neoplasms; medicinal plant; metabolism; Neoplasms, Experimental; pathology; Saxifragaceae; tumor cell line; Wistar rat; Graptopetalum paraguayense; Rattus; Rhodiola rosea; Animals; Carcinoma, Hepatocellular; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Humans; Liver Neoplasms; Male; Neoplasm Proteins; Neoplasms, Experimental; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar; Reactive Oxygen Species; Saxifragaceae
Publisher
Public Library of Science
Type
journal article