Cytotoxic effect and mechanism inducing cell death of α-mangostin liposomes in various human carcinoma and normal cells

Abstract

The aims of this study were to develop α-mangostin liposomes as well as to evaluate their physicochemical properties and cytotoxic activity. α-Mangostin liposomes were prepared using the reverse-phase evaporation method with lipid composition of phosphatidylcholine to cholesterol at 7 : 3 molar ratios; their physicochemical properties and antiproliferative activity were assessed using an MTT assay in four human carcinoma cells [that is, human lung epithelial carcinoma (Calu-3), human colon carcinoma (HT-29), human breast carcinoma (MCF-7), and human colon carcinoma (Caco-2) cells], and two human normal cells [that is, human dermal fibroblasts (HDF) and human adult low-calcium elevated temperature (HaCaT) keratinocytes]. Determinations of morphological changes and oligonucleosomal DNA fragments were also carried out. The liposomal dispersions obtained were unilamellar vesicles as confirmed by cryotransmission and freeze-fracture electron microscopy with a particle size of 114 nm and a ζ potential of -2.56 mV. The P-NMR spectra showed that α-mangostin molecules orientated in the phospholipid bilayer membrane. The α-mangostin could appreciably be entrapped with an efficiency and loading of 81 and 4%, respectively. The antiproliferative activity of α-mangostin liposomes in various cancer and normal cells showed a dose-dependent inhibition in all treated cell lines. The antiproliferative effect of α-mangostin liposomes was found to be associated with apoptosis, with differences in sensitivity among the cell lines treated.

Search for New Type of Anticancer Drugs with High Tumor Specificity and Less Keratinocyte Toxicity

“…In our work, we have demonstrated that [3] and [4] are two new compounds that showed the highest TS and potencyselectivity expression values among the compounds tested, and they exhibited much less keratinocyte toxicity compared to doxorubicin and 5-FU (Figure 4). Chemical modification of these lead compounds by introduction of appropriate functional groups is a crucial step towards manufacturing new types of anticancer drugs with reduced keratinocyte toxicity.…”

“…Compound [3] induced apoptotic cell death in a human OSCC cell line, possibly by down-regulating the glycerophospholipid pathway. Quantitative structure−activity relationship analysis demonstrated that the tumor specificities of [3] and [4] Previous studies have focused on the mechanism of apoptosis induction by anticancer drugs rather than the demonstration of their tumor specificity.…”

“…Quantitative structure−activity relationship analysis demonstrated that the tumor specificities of [3] and [4] Previous studies have focused on the mechanism of apoptosis induction by anticancer drugs rather than the demonstration of their tumor specificity. Most anticancer drugs induce similar morphological changes to those observed during the developmental process (eliminating unnecessary tissues and harmful cells).…”

“…It is well known that administration of anticancer agents induces skin toxicity (1)(2)(3)(4)(5)(6)(7). This prompted us to re-evaluate the cytotoxicity and tumor specificity of anticancer drugs.…”

Existence of α‐mangostin conformers and effects of aprotic and protic solvents on their equilibria, UV–Vis spectra, and chemical descriptors: Density functional theory and time‐dependent density functional theory study

“…α-Mangostin has been extracted from the rind of mangosteen fruit using 1,2-propanediol-betaine, [2] ethyl acetate, [3] and supercritical CO 2 [4] as a green solvent, and from the pericarp with water, [5] and water at 65 C [6] and purification through solid phase extraction. [7] α-Mangostin has been reported to have anti-acne activity, [8] inhibit mutant IDH1, [9] prevent and treat hepatocellular carcinoma, [10] and exhibit antiinflammatory, [11][12][13][14] antibacterial, [15,16] antitumor, [17,18] and antimetastatic properties in many cancer cell types. [19] The biological activities and pharmacological properties of α-mangostin as an antineoplastic agent, antioxidant, antiproliferation agent for the induction of apoptosis, [20] and as a lysine-specific demethylase 1 (LSD1) inhibitor against tumor metastasis [21] have been reviewed.…”