Zerumbone-loaded nanostructured lipid carrier induces apoptosis in human colorectal adenocarcinoma (Caco2) cell line

The incorporation of zerumbone (Zer) into nanostructured lipid carrier (NLC) is hypothesized to increase the efficacy of the drug. Nanostructured lipid carrier has sustained-drug release characteristics and is able to improve the solubility and bioavailability of the lipophilic drug. In this study, the anti-cancer effect of Zer was tested on human colorectal adenocarcinoma (Caco-2) cell line. The effect of Zer, zerumbone-loaded nanostructured lipid carrier (Zer-NLC) and NLC on the Caco-2 cell viability were determined using the MTT assay. The treatment concentration ranges from 0 to 120 μM at four different time intervals (i.e., 0 h, 24 hrs, 48 hrs and 72 hrs) were evaluated. At 24 hrs, the half-growth inhibitory concentration (GI50) of Zer-NLC (i.e., 4.25 μM) is lower than that of Zer (i.e., 23.75 μM). However, Zer outperformed the Zer-NLC at the subsequent time points. Similar trend was observed in other parameters including the cytostatic concentration (CC) and half-lethal concentration 50 (LC50). Phase contrast imaging and AO/PI fluorescence staining were performed at the CC and LC50 values. The morphological changes and the apoptosis features could be seen in cells treated with Zer and Zer-NLC while cells treated with NLC showed minor morphological changes. The cells treated with Zer-NLC demonstrated a slightly slower progression of apoptosis, which could be due to the controlled release of Zer from the NLC matrix. It was concluded that the incorporation of Zer into NLC did not compromise the potency and efficacy of the drug

Zerumbone-loaded nanostructured lipid carrier induces apoptosis of canine mammary Adenocarcinoma cells

Canine mammary gland tumor (CMT) is the most common tumor in intact female dog. Zerumbone (ZER) has promising anticancer properties, but plagued with poor water solubility, poor absorption, bioavailability, and delivery to target tissues. To solubilize, ZER was loaded into nanostructured lipid carrier (NLC) to produce ZER-loaded NLC (ZER-NLC). Te objectives of this study were to determine the antiproliferative efect and the mode of cell death induced by ZER-NLC and ZER on a canine mammary gland tumor (CMT) adenocarcinoma primary cell line. Tere was no signifcant diference (p>0.05) between ZER-NLC and ZER treatments in the inhibition of CMT cell proliferation; thus, the loading of ZER into NLC did not compromise the cytotoxic efect of ZER. Microscopically, ZER-NLC- and ZER-treated CMT cells showed apoptotic cell morphology. ZER-NLC and ZER treatments signifcantly downregulated the antiapoptotic Bcl-2 and upregulated the proapoptotic Bax gene expressions in CMT cells. Both ZER-NLC and ZER-treated CMT cells showed signifcant (p<0.0001) increases in caspase-8, -9, and -3/7 protein activities. In conclusion, ZER-NLC induced CMT cell death via regulation of Bcl-2 and Bax gene expressions and caspase activations, indicating the involvement of both the intrinsic and extrinsic pathways of apoptosis. Tis study provided evidences for the potential of ZERNLC as an anticanine mammary gland adenocarcinoma chemotherapy

Development of erythropoietin receptor-targeted drug delivery system against breast cancer using tamoxifen-loade nanostructured lipid carriers

Tamoxifen (TAM) has been used in the treatment of breast cancers and is supplemented with erythropoietin (EPO) to alleviate the cancer-related anemia. The purported deleterious effects caused by the use of EPO with chemotherapeutic agents in the treatment of cancer-related anemia vary across studies and remain controversial. The use of nanoparticles as a drug delivery system has the potential to improve the specificity of anticancer drugs. In this study, we simultaneously incorporated two pharmacological active ingredients in one nanocarrier to develop EPO-conjugated TAM-loaded lipid nanoparticles (EPO-TAMNLC), a targeted delivery system, to enhance the cytotoxic activity while reducing the side effects of the ingredients. The effect of temperature in modulating the thermodynamic parameters associated with the binding of EPO and TAMNLC was assessed using isothermal titration calorimetry, while the unfolding of EPO structure was determined using fluorescence-quenching approach. The association efficiency of EPO and TAMNLC was 55.43%. Unlike binding of albumin to TAMNLC, the binding of EPO to TAMNLC occurred through endothermic and entropy-driven reaction. The EPO-TAMNLC formulation was stable because of the hydrophobic interaction and the high free energy, suggesting the spontaneity of the interactions between EPO and TAMNLC. The EPO-TAMNLC enhanced the in vitro cytotoxicity of TAM to MCF-7 cells. The EPO surface-functionalized TAMNLC could sequentially deliver EPO and TAM as well as improving site-specific delivery of these therapeutic compounds

Zerumbone-Loaded Nanostructured Lipid Carrier Induces Apoptosis of Canine Mammary Adenocarcinoma Cells

Canine mammary gland tumor (CMT) is the most common tumor in intact female dog. Zerumbone (ZER) has promising anticancer properties, but plagued with poor water solubility, poor absorption, bioavailability, and delivery to target tissues. To solubilize, ZER was loaded into nanostructured lipid carrier (NLC) to produce ZER-loaded NLC (ZER-NLC). The objectives of this study were to determine the antiproliferative effect and the mode of cell death induced by ZER-NLC and ZER on a canine mammary gland tumor (CMT) adenocarcinoma primary cell line. There was no significant difference (p>0.05) between ZER-NLC and ZER treatments in the inhibition of CMT cell proliferation; thus, the loading of ZER into NLC did not compromise the cytotoxic effect of ZER. Microscopically, ZER-NLC- and ZER-treated CMT cells showed apoptotic cell morphology. ZER-NLC and ZER treatments significantly downregulated the antiapoptotic Bcl-2 and upregulated the proapoptotic Bax gene expressions in CMT cells. Both ZER-NLC and ZER-treated CMT cells showed significant (p<0.0001) increases in caspase-8, -9, and -3/7 protein activities. In conclusion, ZER-NLC induced CMT cell death via regulation of Bcl-2 and Bax gene expressions and caspase activations, indicating the involvement of both the intrinsic and extrinsic pathways of apoptosis. This study provided evidences for the potential of ZER-NLC as an anticanine mammary gland adenocarcinoma chemotherapy