peonidin-3-glucoside and Liver-Neoplasms

In this study, the anthocyanin from Lonicera caerulea 'Beilei' fruit (ABL) was extracted and purified. The purified component (ABL-2) was then evaluated for its anti-tumor properties on human hepatoma cells (SMMC-7721) in vitro and the murine hepatoma cells (H22) in vivo. In vitro, ABL-2 not only significantly inhibited the growth of SMMC-7721 cells, but also remarkably blocked the cells' cycle in G2/M phase, inducing DNA damage and eventually leading to apoptosis. In vivo, ABL also killed tumor cells, inhibited tumor growth, and improved the survival status of H22 tumor-bearing mice. These effects were associated with an increase in the activities of antioxidase and a decrease in the level of lipid peroxidation, as evidenced by changes in SOD, GSH-Px, GSH, and MDA levels. In addition, ABL-2 also regulated the levels of immune cytokines including IL-2, IFN-γ, and TNF-α. These results revealed that ABL-2 exerts an effective anti-tumor effect by dynamically adjusting the REDOX balance and improving the immunoregulatory activity of H22 tumor-bearing mice. High performance liquid chromatography (HPLC) analysis revealed that cyanidin-3,5-diglucoside (8.16 mg/g), cyanidin-3-glucoside (387.60 mg/g), cyanidin-3-rutinoside (23.62 mg/g), and peonidin-3-glucoside (22.20 mg/g) were the main components in ABL-2, which may contribute to its anti-tumor activity.

Topics: Animals; Anthocyanins; Antineoplastic Agents; Antioxidants; Apoptosis; Carcinoma, Hepatocellular; Cell Line, Tumor; Cytokines; DNA Damage; Fruit; G2 Phase Cell Cycle Checkpoints; Glucosides; Humans; Lipid Peroxidation; Liver Neoplasms; Lonicera; Male; Mice; Plant Extracts

Anthocyanins belong to a class of flavonoids exhibiting antioxidant and anti-inflammatory actions as well as a variety of chemotherapeutic effects. However, little is known about the cellular and molecular mechanism of anticancer activity. In this study, we investigated if the anthocyanins (delphinidin-3,5-diglucoside: cyanidin-3,5-diglucoside: petunidin-3,5-diglucoside: delphinidin-3-glucoside: malvdin-3,5-diglucoside: peonidin-3,5-diglucoside: cyanidin-3-glucoside: petunidin-3-glucoside: peonidin-3- glucoside: malvidin-3- glucoside = 27:63:8.27:1:2.21:2.21:6.7:1.25:5.72:1.25) [corrected] isolated from meoru (Vitis coignetiae Pulliat) exerted antiproliferative and anti-invasive and apoptotic effects on human hepatoma Hep3B cells. It was found that the anthocyanins could inhibit cell growth by 75% at the concentration of 400 microg/mL for 48 h. Flow cytometric analysis showed that the anthocyanins increased the amount of DNA fragments (sub-G1 fraction) in a dose-dependent manner, which is closely related to mitochondrial dysfunction and reduction in antiapoptotic proteins (Bcl-2, xIAP, cIAP-1, and cIAP-2). The anthocyanins also significantly inhibited the migration and invasion of Hep3B cells through a matrigel-coated chamber. Taken together this study indicates that the anthocyanins from meoru have antiproliferative and anti-invasive effects and may induce apoptosis through the activation of the mitochondrial pathway and inhibition of antiapoptotic proteins. This study provides evidence that the anthocyanins isolated from meoru might be useful in the treatment of human hepatitis B-associated hepatoma.

Topics: Anthocyanins; Apoptosis; bcl-2-Associated X Protein; bcl-X Protein; Blotting, Western; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Movement; DNA Fragmentation; Dose-Response Relationship, Drug; Flow Cytometry; Glucosides; Humans; Inhibitor of Apoptosis Proteins; Liver Neoplasms; Membrane Potential, Mitochondrial; Neoplasm Invasiveness; Proto-Oncogene Proteins c-bcl-2; Reverse Transcriptase Polymerase Chain Reaction; Vitis; X-Linked Inhibitor of Apoptosis Protein