Novel Microemulsion of Tanshinone IIA, Isolated from Salvia miltiorrhiza Bunge, Exerts Anticancer Activity Through Inducing Apoptosis in Hepatoma Cells

Abstract

Natural product Tanshinone IIA (TanIIA) induces apoptosis and differentiation in hepatocellular carcinoma (HCC) cells, but its clinical use is limited due to poor water solubility and lack of appropriate formulations for drug delivery. In this study, we capsulated TanIIA into a microemulsion (ME) that was composed of phospholipid, ethyl oleate, glycerol and pluronic F68. We then determined the anticancer effects and mechanisms of action for TanIIA ME with in vitro and in vivo HCC models. The mRNA and protein levels of apoptosis-related molecules (Bcl-2, Bax and caspase-3) were analyzed in murine hepatoma H22 cells and H22 tumor-bearing mice by flow cytometry, RT-PCR and immunofluorescence staining. Compared with the groups treated with empty ME and drug solution, the mRNA levels of Bax and caspase-3 were up-regulated, and the mRNA and protein levels of Bcl-2 were down-regulated in H22 cells treated with TanIIA ME in a dose-dependent manner. The mRNA and protein levels of Bax and caspase-3 were up-regulated and the Bcl-2 levels were also down-regulated in animals treated with TanIIA ME in a dose-dependent manner. Our results suggest that as a novel drug delivery system, microemulsion enhances the antitumor effects of TanIIA.

Tanshinone IIA Inhibits Glutamate‐Induced Oxidative Toxicity through Prevention of Mitochondrial Dysfunction and Suppression of MAPK Activation in SH‐SY5Y Human Neuroblastoma Cells

“…Together, these findings support the involvement of apoptosis pathways in the neuroprotective effects of tanshinone IIA. Interestingly, however, tanshinone IIA is also found to induce apoptosis of tumor cells by upregulating expression of proapoptotic proteins [55]. These seemingly conflicting observations suggest that tanshinone IIA may initiate context-dependent signals and responses in a specific cellular environment; in the current circumstance, for instance, the metabolically stressed neuronal cells and the metabolically modified tumor cells have distinct signaling response modes and gene expression patterns [56].…”

Anti-Colon Cancer Effects of 6-Shogaol Through G2/M Cell Cycle Arrest by p53/p21-cdc2/cdc25A Crosstalk

“…Total RNA of HCT-116 cells was extracted after exposure to 6-shogaol for 48 h. cDNA and the first strand of the transcription product were prepared (Ma et al, 2013). The expression of human cell cycle and apoptosis related genes were determined using a PCR array (Cat# PAHS-020E, 84 cell cycle genes covered; Cat# PAHS-012, 84 apoptosis genes covered; SABiosciences, Frederick, MD) following the manufacturer's instructions (Wang et al, 2009).…”

TPGS-g-PLGA/Pluronic F68 mixed micelles for tanshinone IIA delivery in cancer therapy

“…However, the clinical application of TAN for anticancer therapy is hindered by its low water-solubility, poor cellular uptake , short half-life, and first pass metabolism (Zhang et al, 2012b;Yu et al, 2007). Many colloidal carriers including polymeric micelles (Wang et al, 2014), emulsions (Chu et al, 2012), micro-emulsions (Ma et al, 2013), and nanoparticles have been used to improve the solubility of TAN. However, the cytotoxicity and bioavailability of TAN still need to be improved.…”