Anacardic acid enhances the anticancer activity of liposomal mitoxantrone towards melanoma cell lines – in vitro studies

Abstract

This paper describes a novel formulation of antineoplastic drug: mitoxantrone loaded into liposomal carriers enriched with encapsulated anacardic acid in the liposomal bilayer using a vitamin C gradient. Anacardic acid is a potent epigenetic agent with anticancer activity. This is the first liposomal formulation to combine an actively encapsulated drug and anacardic acid. The liposomes were characterized in terms of basic parameters, such as size, zeta potential, optimal drug-to-lipid ratio, loading time and temperature, and stability at 4°C and in human plasma in vitro. The formulation was found to be stable, and the loading process was rapid and efficient (drug-to-lipid ratio of up to 0.3 with over 90% efficiency in 5 minutes). The cytotoxicity of these formulations was assessed using the human melanoma cell lines A375 and Hs294T and the normal human dermal fibroblast line. The results showed that anacardic acid and to a smaller extent vitamin C significantly increased the cytotoxicity of the drug towards melanoma compared to ammonium sulfate liposomes. On the other hand, vitamin C and anacardic acid both protected normal cells from damage caused by the drug. The formulation combining anacardic acid, vitamin C, and mitoxantrone showed promising results in terms of cytotoxicity and cytoprotection. Therefore, it has potential for anticancer treatment.

Potentialities of Cashew Nut (Anacardium occidentale) By-Product for Pharmaceutical Applications: Extraction and Purification Technologies, Safety, and Anti-inflammatory and Anti-arthritis Activities

“…The biological effects of compounds isolated from A. occidentale cashew nut bark oil have been widely evaluated and have indicated that these substances reduce and induce cell death in tumor cells such as in the breasts, kidneys, prostate, colon, lungs, and melanomas (Huang et al 2010;Hemshekhar et al 2012;Seong et al 2013;Legut et al 2014). The mechanism by which these substances present anti-tumor potential is by inhibiting histone acetyltransferase p300, which acts on DNA transcription (Balasubramanyam et al 2003).…”

Drug discovery and therapeutic delivery for the treatment of B and T cell tumors

“…These delivery methods include dendrimers, nanogels, nanoparticles, and liposomes, and the diversity among them provide tailor made properties for different malignancy types. Liposomal carriers with encapsulated anacardic acid (epigenetic drug) in the liposomal bilayer with a vitamin C gradient, loaded with mitoxantrone has been developed 159 . The efficacy of N-isopropylacrylamide (NIPAM)-based biodegradable nanogels with decitabine was shown in drug resistant solid tumors and leukemia cells.…”

Advancements in the delivery of epigenetic drugs

“…This could include delivering nucleic acids such as RNA sequences which work through epigenetic mechanisms. A novel formulation involving enriched liposomal carriers with encapsulated anacardic acid in the liposomal bilayer with a vitamin C gradient, loaded with mitoxantrone has been developed [77]. The epigenetic agent is the anacardic acid which has been shown to have anticancer properties.…”

“…The cytotoxicity of mitoxantrone was shown to be enhanced by the anacardic acid and the vitamin C when used on human melanoma cell lines A375 and Hs294T. However, these same two compounds – anacardic acid and vitamin C – were cytoprotective when used on a normal human fibroblast line [77]. …”