Curcumin Nanoparticles and Their Cytotoxicity in Docetaxel-Resistant Castration-Resistant Prostate Cancer Cells.

Irin Tanaudommongkon,Xiaowei Dong,Asama Tanaudommongkon,Priyanka Prathipati,Joey Trieu Nguyen,Evan T Keller

doi:10.3390/biomedicines8080253

Abstract

Most prostate cancer patients develop resistance to anti-androgen therapy. This is referred to as castration-resistant prostate cancer (CRPC). Docetaxel (DTX) is the mainstay treatment against CRPC. However, over time patients eventually develop DTX resistance, which is the cause of the cancer-related mortality. Curcumin (CUR) as a natural compound has been shown to have very broad pharmacological activities, e.g., anti-inflammatory and antioxidant properties. However, CUR is very hydrophobic. The objective of this study was to develop CUR nanoparticles (NPs) and evaluate their cytotoxicity in DTX-resistant CRPC cells for the treatment of DTX-resistant CRPC. We tested solubility of CUR in different lipids and surfactants. Finally, Miglyol 812 and D-alpha-tocopheryl poly (ethylene glycol) succinate 1000 (TPGS) were chosen to prepare lipid-based NPs for CUR. We fully characterized CUR NPs that had particle size < 150 nm, high drug loading (7.5%), and entrapment efficiency (90%). Moreover, the CUR NPs were successfully lyophilized without using cryoprotectants. We tested the cytotoxicity of blank NPs, free CUR, and CUR NPs in sensitive DU145 and PC3 cells as well as their matching docetaxel-resistant cells. Cytotoxicity studies showed that blank NPs were very safe for all tested prostate cancer cell lines. Free CUR overcame the resistance in PC3 cells, but not in DU145 cells. In contrast, CUR NPs significantly increased CUR potency in all tested cell lines. Importantly, CUR NPs completely restored CUR potency in both resistant DU145 and PC3 cells. These results demonstrate that the CUR NPs have potential to overcome DTX resistance in CRPC.

Highlights

Prostate cancer (PCa) is the second-most-frequent cancer diagnosis in men and the fifth leading cause of cancer death worldwide [1]
Most patients will develop resistance to anti-androgen therapy and high metastases, which is referred to as castration-resistant prostate cancer (CRPC) [2]
We studied the cytotoxicity of CUR MT NPs in both resistant and sensitive

Summary

Introduction

Prostate cancer (PCa) is the second-most-frequent cancer diagnosis in men and the fifth leading cause of cancer death worldwide [1]. Anti-androgen is the first line treatment for PCa. most patients will develop resistance to anti-androgen therapy and high metastases, which is referred to as castration-resistant prostate cancer (CRPC) [2]. Drug Administration (FDA) as the mainstay treatment against CRPC and has been shown to improve the survival rate of men with metastatic CRPC [3]. DTX resistance, which is the cause of the cancer-related mortality. Multiple mechanisms exist for drug resistance and a drug is not confronted by a single mechanism. One well-known mechanism of drug resistance is overexpression of P-glycoprotein (P-gp), a transporter that can efflux the drugs out of Biomedicines 2020, 8, 253; doi:10.3390/biomedicines8080253 www.mdpi.com/journal/biomedicines

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