Abstract
Oridonin (ORI), a famous diterpenoid from Chinese herbal medicine, has drawn rising attention for its remarkable apoptosis and autophagy-inducing activity in human cancer therapy, while clinical application of ORI is limited by its strong hydrophobicity and rapid plasma clearance. The purpose of this study was to evaluate whether the antitumor activity of ORI could be enhanced by loading into solid lipid nanoparticles (SLNs). ORI-loaded SLNs were prepared by hot high pressure homogenization with narrow size distribution and good entrapment efficacy. MTT assay indicated that ORI-loaded SLNs enhanced the inhibition of proliferation against several human cancer cell lines including breast cancer MCF-7 cells, hepatocellular carcinoma HepG 2 cells, and lung carcinoma A549 cells compared with free ORI, while no significant enhancement of toxicity to human mammary epithelial MCF-10A cells was shown. Meanwhile, flow cytometric analysis demonstrated that ORI-SLNs induced more significant cell cycle arrest at S and decreased cell cycle arrest at G1/G0 phase in MCF-7 cells than bulk ORI solution. Hoechst 33342 staining and Annexin V/PI assay indicated that apoptotic rates of cells treated with ORI-loaded SLNs were higher compared with free ORI. In summary, our data indicated that SLNs may be a potential carrier for enhancing the antitumor effect of hydrophobic drug ORI.
Highlights
Oridonin (ORI), a tetracycline diterpenoid derived from a traditional Chinese herb Rabdosia rubescens, has been widely used as antibacterial, antinociceptive, and anti-inflammatory agent for years [1,2,3]
Reactive oxygen species (ROS), p53, nuclear factor-kappaB (NFκB), MAPK, and PI3K/Akt pathways have been demonstrated to be involved in the apoptosis and autophagy-inducing effect of ORI [10, 13, 14]
Oridonin-loaded solid lipid nanoparticles (SLNs) were prepared by high pressure homogenization using glyceryl monostearate, oleic acid, and poloxamer 188
Summary
Oridonin (ORI), a tetracycline diterpenoid derived from a traditional Chinese herb Rabdosia rubescens, has been widely used as antibacterial, antinociceptive, and anti-inflammatory agent for years [1,2,3]. ORI has been clinically used for treating cancer and its antitumor mechanisms of ORI have been well documented [4,5,6,7]. ORI exerts its antitumor effect mainly by inhibiting proliferation [8], inducing cell cycle arrest [5], apoptosis, and autophagy [9,10,11], as well as halting the tumor angiogenesis and metastasis [12]. Though solid lipid nanoparticles (SLNs) conjunct with lipid composition, water-soluble component and surfactant could load the poorly water-soluble drug and improve its solubility; the specific studies of the pharmacology function of drugloaded SLNs on cancer cells still need further investigation. Here exists a critical need to explore and evaluate whether SLNs was a worthy delivery system to treat cancer. The pharmaceutical actions of cell viability, cellular uptake, cell cycle arrest, and apoptosis treated with
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