Effect of β-cyclodextrin encapsulation on cytotoxic activity of acetylshikonin against HCT-116 and MDA-MB-231 cancer cell lines

Abstract

Acetylshikonin (AcSh), as a red colored pigment found in roots of the plants from family Boraginaceae, showed excellent cytotoxic activity. Due to its hydrophobic nature, and thus poor bioavailability, the aim of this study was to prepare acetylshikonin/β-cyclodextrin (AcSh/β-CD) inclusion complex by using coprecipitation method, characterize obtained system by using UV/VIS, IR and 1H NMR spectroscopy, and determine cytotoxic activity. Phase solubility test indicated formation of AL-type binary system (substrate/ligand ratio was 1:1 M/M), with stability constant Ks of 306.01 M−1. Formation of noncovalent bonds between inner layer of the hole of β-CD and AcSh was observed using spectroscopic methods. Notable changes in chemical shifts of two protons (−0.020 ppm) from naphthoquinone moiety (C6-H and C7-H), as well as protons from hydroxyl groups (−0.013 and −0.009, respectively) attached to C5 and C8 carbons from naphthoquinone part indicate that the molecule of AcSh enters the β-CD cavity from the aromatic side. Cytotoxic activity against HCT-116 and MDA-MB-231 cell lines was measured by MTT test and clonogenic assay. Mechanisms of action of free AcSh and inclusion complex were assessed by flow cytometry. In comparison to free AcSh, AcSh/β-CD showed stronger short-term effect on HCT-116 cells and superior long-term effect on both cell lines. Inclusion complex induced more pronounced cell cycle arrest and autophagy inhibition, and induced increase in accumulation of intracellular ROS more effectively than free AcSh. In conclusion, AcSh/β-CD binary system showed better performances regarding cytotoxic activity against tested tumor cell lines.

Preparation of Gelatin/Carrageenan-Based Color-Indicator Film Integrated with Shikonin and Propolis for Smart Food Packaging Applications

“…The peaks at 3291 and 2928 cm −1 were owing to the O−H stretching and methyl stretching of shikonin. 36 The bands at 1725, 1662, 1414, and 1035 cm −1 were ascribed to the carbonyl group, CC aromatic ring, C−O stretching of alcohol groups, respectively. 36 The band detected at 3328 and 2974 and 2888 cm −1 were due to the O-H groups and methyl (symmetric and asymmetric stretching) groups of propolis, respectively.…”

The Interaction of Heptakis (2,6-di-O-Methyl)-β-cyclodextrin with Mianserin Hydrochloride and Its Influence on the Drug Toxicity

“…This methylated derivative of β-cyclodextrin under 400 µM is still not toxic (Figure 11), and we decided to choose that concentration to investigate whether DM-β-CD can protect Chinese hamster cells from the toxic effects of mianserin hydrochloride, or make the drug more toxic. In the literature [42][43][44], the enclosing of the drug by native β-cyclodextrin macromolecules increased the cytotoxicity against examined tumor cell lines. A similar situation has been observed for DM-β-CD+MIA complexes-but in the presented case, the cell viability of Chinese hamster non-tumor cells incubated with the complexes was remarkably lower when confronted with the viability cells treated only with the 200 µM MIA solution (Figure 12).…”

“…This methylated derivative of β-cyclodextrin under 400 μM is still not toxic (Figure 11), and we decided to choose that concentration to investigate whether DM-β-CD can protect Chinese hamster cells from the toxic effects of mianserin hydrochloride, or make the drug more toxic. In the literature [42][43][44], the enclosing of the drug by native β-cyclodextrin macromolecules increased the The most favorable free energy of binding has been calculated for the complex with the MIA-β-CD ratio equal to 1:3, except for the R-(−)-MIA•HCl enantiomer (Table 2). In Figure 5, the examples of the MIA-β-CD complex geometries for both enantiomers with stoichiometry 1:3 obtained by MD simulations have been placed.…”

Pharmacology, toxicity and pharmacokinetics of acetylshikonin: a review

“…Acetylshikonin suppressed the proliferation of MDA-MB-231 cells through cell cycle arrest at G0/G1 phases, autophagy inhibition, and accumulation of intracellular ROS (Vukic et al. 2020 ). NF-κB-dependent productions of cytokines and MMP-9 were found to be decreased after acetylshikonin treatment, which led to the inhibition of the proliferation and invasion of PANC-1 cells (Cho and Choi 2015 ).…”

“…Acetylshikonin/b-cyclodextrin inclusion complex decreased Bcl-2/Bax ratio and activated caspase-3, thereby inducing apoptosis in HCT116 cells. Moreover, this inclusion complex exerted long-term cytotoxicity via suppression of autophagy and excess accumulation of intracellular reactive oxygen species (ROS) (Vukic et al 2020). Acetylshikonin suppressed the proliferation of colon cancers (HT29, DLD-1, and Caco-2 cells) in a dose-dependent manner.…”