Tanshinone IIA is the most abundant diterpene quinone in Danshen, Salviae miltiorrhizae Radix, a widely prescribed traditional herbal medicine that is used to treat cardiovascular and inflammatory diseases. Recently, tanshinone IIA was demonstrated to induce cell death and apoptosis in a variety of tumors. However, the effect of tanshinone IIA on human colon cancer cells is not clearly understood yet. In this study, the antigrowth and apoptosis-eliciting effects of tanshinone IIA, as well as its cellular mechanisms of actions, were investigated in Colo-205 human colon cancer cells. Tanshinone IIA reduced cell growth in a concentration-dependent manner, inducing apoptosis accompanied by an increase in TUNEL staining and by an increased percentage of cells in the sub-G1 fraction. The expression of p53 and p21 and mitochondrial cytochrome c release were increased in tanshinone IIA-treated cells. In addition, the expression of Fas proteins was up-regulated by tanshinone IIA. Tanshinone IIA-induced catalytic activation of caspases was confirmed by cleavage of caspase-8 and caspase-3. These findings suggest that tanshinone IIA induces apoptosis in Colo-205 cells through both mitochondrial-mediated intrinsic and Fas-mediated extrinsic caspase cell-death pathways. Accordingly, the chemotherapeutic potential of tanshinone IIA for colon cancer warrants further study.

BackgroundMicroglial cells are the predominant immune cells in malignant brain tumors, but tumors may release some factors to reduce their defensive functions. Restoration of the anti-cancer function of microglia has been proposed as a treatment modality for glioblastoma. We examined the effect of intra-cranially administered recombinant adeno-associated virus encoding interleukin-12 (rAAV2/IL12) on transfection efficiency, local immune activity and survival in a rat model of glioblastoma multiforme.MethodsF344 rats were injected with rAAV2/IL12 and implanted with syngeneic RG2 cells (glioblastoma cell line). Intracerebral interleukin-12 and interferon-γ concentrations were determined by ELISA. Activation of microglia was determined by expressions of ED1 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) which were evaluated by Western blotting and immunohistochemistry. The proliferation of cancer cells was evaluated with Ki67 immunohistochemistry and apoptosis of cancer cells with TUNEL.ResultsThe brains treated with rAAV2/IL-12 maintained high expression of interleukin-12 and interferon-γ for at least two months. In syngeneic tumor model, brains treated with rAAV2/IL12 exhibited more infiltration of activated microglia cells as examined by ED1 and TRAIL stains in the tumor. In addition, the volume of tumor was markedly smaller in AAV2/IL12-treated group and the survival time was significantly longer in this group too.ConclusionThe intra-cerebrally administered rAAV2/IL-12 efficiently induces long lasting expression of IL-12, the greater infiltration of activated microglia cells in the tumor associated improved immune reactions, resulting in the inhibited growth of implanted glioblastoma and the increased survival time of these rats.

Tan-IIA exerts powerful inhibitory effects in gastric cancer AGS cells. The PI3K/AKT/mTOR pathway is one of the most frequently dysregulated kinase cascades in human cancer. In the present study, we investigated the protein expression levels of PI3K, AKT and mTOR in AGS cells treated with Tan-IIA both in vitro and in vivo. The AGS cells were treated with Tan-IIA for different durations in vitro. In the in vivo study, AGS cell xerograft SCID mice were treated with Tan-IIA for 8 weeks. Subsequently, the protein expression of EGFR, IGFR, PI3K, AKT and mTOR was measured by western blotting. The results showed that Tan-IIA was able to decrease the protein expression levels of EGFR, IGFR, PI3K, AKT and mTOR significantly and dose-dependently in vitro and in vivo. In conclusion, these findings indicate Tan-IIA could inhibit AGS cells through decreasing the protein expression of EGFR, IGFR and blocking PI3K/AKT/mTOR pathway both in vitro and in vivo.

The ability of tanshinone IIA (Tan-IIA) to inhibit the proliferation of human breast cancer cell lines in vitro and in vivo is well documented. However, the molecular mechanisms have not been fully elucidated. In the present study, MDA-MB-231 cells were treated with different concentrations of Tan-IIA for 48 h, followed by protein extraction for western blotting. For an in vivo study, MDA-MB-231 cells were implanted directly into female SCID mice which were divided randomly into three groups to be treated with vehicle, Tan-IIA (20 mg/kg) and Tan-IIA (60 mg/kg) every other day orally, with treatment starting 4 weeks after inoculation with the MDA-MB-231 cells. The results showed that Tan-IIA inhibited the proliferation of MDA-MB-231 cells and decreased the protein expression of LC3-II and Erb-B2 in vitro. Treatment with Tan-IIA (20 or 60 mg/kg) for 90 days resulted in a reduction in tumor size and weight compared to the control group. The protein expression of NF-κBp65 was reduced, while caspase-3 was up-regulated compared to the control group. These findings indicate that Tan-IIA inhibits tumor growth in a MDA-MB-231 xenograft animal model. One of the molecular mechanisms may be through a decrease in NF-κBp65 and an increase in caspase-3 expression.