The Effect of Liposomal Diallyl Disulfide and Oxaliplatin on Proliferation of Colorectal Cancer Cells: In Vitro and In Silico Analysis

Abstract

Diallyl disulfide (DADS) is one of the main bioactive organosulfur compounds of garlic, and its potential against various cancer models has been demonstrated. The poor solubility of DADS in aqueous solutions limits its uses in clinical application. The present study aimed to develop a novel formulation of DADS to increase its bioavailability and therapeutic potential and evaluate its role in combination with oxaliplatin (OXA) in the colorectal cancer system. We prepared and characterized PEGylated, DADS (DCPDD), and OXA (DCPDO) liposomes. The anticancer potential of these formulations was then evaluated in HCT116 and RKO colon cancer cells by different cellular assays. Further, a molecular docking-based computational analysis was conducted to determine the probable binding interactions of DADS and OXA. The results revealed the size of the DCPDD and DCPDO to be 114.46 nm (95% EE) and 149.45 nm (54% EE), respectively. They increased the sensitivity of the cells and reduced the IC50 several folds, while the combinations of them showed a synergistic effect and induced apoptosis by 55% in the cells. The molecular docking data projected several possible targets of DADS and OXA that could be evaluated more precisely by these novel formulations in detail. This study will direct the usage of DCPDD to augment the therapeutic potential of DCPDO against colon cancer in clinical settings.

Lipid-Based Nanoparticle Formulation of Diallyl Trisulfide Chemosensitizes the Growth Inhibitory Activity of Doxorubicin in Colorectal Cancer Model: A Novel In Vitro, In Vivo and In Silico Analysis

“…The UV spectrophotometer was used to evaluate the entrapment efficiency (EE) of DATS as described earlier [ 46 , 47 ]. The liposomes were lysed with 0.5% Triton-X-100 and the amount of DATS entrapped in the liposomes was calculated by applying the formula.…”

“…The size of the DATS/DOXO-loaded and empty liposomes were evaluated in PBS, while the zeta potential as well as PDI of these preparations were analysed in the deionized water by dynamic light scattering (DLS) in Zetasizer Nano system (Malvern Instruments, Malvern, Worcestshire, UK) as described earlier [ 46 , 47 ].…”

“…The stability of DATSL and DOXL was evaluated in the PBS at 37 °C by incubating the respective liposomal formulations from 1–72 h, as reported previously [ 46 , 47 ]. In brief, 1 mL of DATSL/DOXL was incubated in the dialysis bags (MWCO 3.5 kDA), for 72 h against 20 mL of 9% sucrose solution in PBS with continuous gentle shaking.…”

“…Thus, preparing suitable formulations of DATS can overcome this limitation to utilize its efficacy against several pathological conditions. Recently, we prepared the PEG-coated DSPC/Chol liposomes of diallyl disulfide and thymoquinone and demonstrated their stability as well as efficacy against HCT116 and RKO colon cancer and A549 and H460 lung cancer lines respectively [ 46 , 47 ]. The liposomal formulation of diallyl disulfide increased the efficacy oxaliplatin by inducing ROS, consequently leading to apoptosis [ 47 ].…”

“…Recently, we prepared the PEG-coated DSPC/Chol liposomes of diallyl disulfide and thymoquinone and demonstrated their stability as well as efficacy against HCT116 and RKO colon cancer and A549 and H460 lung cancer lines respectively [ 46 , 47 ]. The liposomal formulation of diallyl disulfide increased the efficacy oxaliplatin by inducing ROS, consequently leading to apoptosis [ 47 ]. Earlier, we also prepared the pH-sensitive liposomal formulations of diallyl sulfide and showed its chemopreventive potential in dimethyl-benz-a-anthracene (DMBA) induced skin papilloma [ 48 ].…”