Synergistic combinations of tanshinone IIA and trans-resveratrol toward cisplatin-comparable cytotoxicity in HepG2 human hepatocellular carcinoma cells

Abstract

Aim: To determine the combinative effects of tanshinone IIA (Tan IIA) and trans-resveratrol (Resv) on cytotoxicity, apoptosis, cell-cycle arrest and DNA fragmentation in HepG2 human liver cancer cells.

Materials and methods: Cytotoxicity was detected by the cell proliferation and cytotoxicity WST-1 assay. Cell-cycle arrest and apoptosis were determined using flow cytometry analysis. DNA fragments were separated by gel electrophoresis.

Results: Tan IIA and Resv at mixture ratios of 1/2:1/2 and 1/3:2/3 exerted synergistic cytotoxicity comparable to that of cisplatin. Elevated proportions of sub-G1 and apoptotic cells were respectively found in the combinative treatments in comparison with hypothetic values of additive effects. Moreover, a more intensive pattern of apoptotic DNA fragmentation was visualized in combined treatments than in individual ones.

Conclusion: Combining Tan IIA and Resv causes synergistic cisplatin-comparable, cytotoxicity and robustly induces apoptosis, sub-G1 cell cycle arrest and DNA fragmentation. This study provides evidence supporting further pre-clinical investigations of the combinational synergism.

Keywords: Tanshinone IIA; apoptosis; cell cycle arrest; cisplatin; synergistic combination; trans-resveratrol.