Propylene Glycol Caprylate-Based Nanoemulsion Formulation of Plumbagin: Development and Characterization of Anticancer Activity

Plumbagin, a bioactive naphthoquinone, has demonstrated potent antitumor potential. However, plumbagin is a sparingly water-soluble compound; therefore, clinical translation requires and will be facilitated by the development of a new pharmaceutical formulation. We have generated an oil-in-water nanoemulsion formulation of plumbagin using a low-energy spontaneous emulsification process with propylene glycol caprylate (Capryol 90) as an oil phase and Labrasol/Kolliphor RH40 as surfactant and cosurfactant excipients. Formulation studies using Capryol 90/Labrasol/Kolliphor RH40 components, based on pseudoternary diagram and analysis of particle size distribution and polydispersity determined by dynamic light scattering (DLS), identified an optimized composition of excipients for nanoparticle formulation. The nanoemulsion loaded with plumbagin as an active pharmaceutical ingredient had an average hydrodynamic diameter of 30.9 nm with narrow polydispersity. The nanoemulsion exhibited long-term stability, as well as good retention of particle size in simulated physiological environments. Furthermore, plumbagin-loaded nanoemulsion showed an augmented cytotoxicity against prostate cancer cells PTEN-P2 in comparison to free drug. In conclusion, we generated a formulation of plumbagin with high loading drug capacity, robust stability, and scalable production. Novel Capryol 90-based nanoemulsion formulation of plumbagin demonstrated antiproliferative activity against prostate cancer cells, warranting thus further pharmaceutical development.

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Diagnosis of Prostate Cancer and Prostatitis Using near Infra-Red Fluorescent AgInSe/ZnS Quantum Dots

International Journal of Molecular Sciences ◽

10.3390/ijms222212514 ◽

2021 ◽

Vol 22 (22) ◽

pp. 12514

Author(s):

Vuyelwa Ncapayi ◽

Neethu Ninan ◽

Thabang C. Lebepe ◽

Sundararajan Parani ◽

Aswathy Ravindran Girija ◽

...

Keyword(s):

Prostate Cancer ◽

Quantum Dots ◽

Cancer Cells ◽

Near Infrared ◽

Particle Diameter ◽

Spherical Shape ◽

Water Soluble ◽

Prostate Cancer Cells ◽

Intracellular Targeting ◽

Low Toxicity

The link between the microbiome and cancer has led researchers to search for a potential probe for intracellular targeting of bacteria and cancer. Herein, we developed near infrared-emitting ternary AgInSe/ZnS quantum dots (QDs) for dual bacterial and cancer imaging. Briefly, water-soluble AgInSe/ZnS QDs were synthesized in a commercial kitchen pressure cooker. The as-synthesized QDs exhibited a spherical shape with a particle diameter of 4.5 ± 0.5 nm, and they were brightly fluorescent with a photoluminescence maximum at 705 nm. The QDs showed low toxicity against mouse mammary carcinoma (FM3A-Luc), mouse colon carcinoma (C26), malignant fibrous histiocytoma-like (KM-Luc/GFP) and prostate cancer cells, a greater number of accumulations in Staphylococcus aureus, and good cellular uptake in prostate cancer cells. This work is an excellent step towards using ternary QDs for diagnostic and guided therapy for prostate cancer.

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PSMA-Oriented Target Delivery of Novel Anticancer Prodrugs: Design, Synthesis, and Biological Evaluations of Oligopeptide-Camptothecin Conjugates

International Journal of Molecular Sciences ◽

10.3390/ijms19103251 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3251 ◽

Cited By ~ 2

Author(s):

Bing Xu ◽

Fei Zhou ◽

Meng-Meng Yan ◽

De-Sheng Cai ◽

Wen-Bo Guo ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Water Solubility ◽

Water Soluble ◽

Cytotoxic Activities ◽

Prostate Cancer Cells ◽

Selective Toxicity ◽

Induce Cell Cycle Arrest ◽

Mcf 7

Clinical applications of camptothecin (CPT) have been heavily hindered due to its non-targeted toxicity, active lactone ring instability, and poor water solubility. Targeted drug delivery systems may offer the possibility to overcome the above issues as reported. In this research, a series of prostate-specific membrane antigen (PSMA)-activated CPT prodrugs were designed and synthesized by coupling water-soluble pentapeptide, a PSMA hydrolyzing substrate, to CPT through an appropriate linker. The cytotoxicity of CPT prodrugs was masked temporarily until they were hydrolyzed by the PSMA present within the tumor sites, which restored cytotoxicity. The in vitro selective cytotoxic activities of the prodrugs were evaluated against PSMA-expressing human prostate cancer cells LNCaP-FGC and non-PSMA-expressing cancer cells HepG2, Hela, MCF-7, DU145, PC-3 and normal cells MDCK, LO2 by standard methylthiazol tetrazolium (MTT) assay. Most of the newly synthesized CPT prodrugs showed excellent selective toxicity to PSMA-producing prostate cancer cells LNCaP-FGC with improved water solubility. From among the library, CPT-HT-J-ZL12 showed the best cytotoxic selectivity between the PSMA-expressing and the non-PSMA-expressing cancer cells. For example, the cytotoxicity of CPT-HT-J-ZL12 (IC50 = 1.00 ± 0.20 µM) against LNCaP-FGC (PSMA+) was 40-fold, 40-fold, 21-fold, 5-fold and 40-fold, respectively, higher than that against the non-PSMA-expressing cells HepG2 (IC50 > 40.00 µM), Hela (IC50 > 40.00 µM), MCF-7 (IC50 = 21.68 ± 4.96 µM), DU145 (IC50 = 5.40 ± 1.22 µM), PC-3 (IC50 = 42.96 ± 3.69 µM) cells. Moreover, CPT-HT-J-ZL12 exhibited low cytotoxicity (IC50 > 40 μM) towards MDCK and LO2 cells. The cellular uptake experiment demonstrated the superior PSMA-targeting ability of the CPT-HT-J-ZL12, which was significantly accumulated in LNCaP-FGC (PSMA+), while it was minimized in HepG2 (PSMA−) cells. Further cell apoptosis analyses indicated that it showed a dramatically higher apoptosis-inducing activity in LNCaP-FGC (PSMA+) cells than in HepG2 (PSMA−) cells. Cell cycle analysis indicated that CPT-HT-J-ZL12 could induce cell cycle arrest at the S phase.

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Ca2+ movement and cytotoxicity induced by the pyrethroid pesticide bifenthrin in human prostate cancer cells

Human & Experimental Toxicology ◽

10.1177/0960327119855129 ◽

2019 ◽

Vol 38 (10) ◽

pp. 1145-1154 ◽

Cited By ~ 2

Author(s):

J-M Chien ◽

W-Z Liang ◽

W-C Liao ◽

C-C Kuo ◽

C-T Chou ◽

...

Keyword(s):

Prostate Cancer ◽

Endoplasmic Reticulum ◽

Cell Viability ◽

Cancer Cells ◽

Water Soluble ◽

Human Prostate ◽

Human Prostate Cancer ◽

Prostate Cancer Cells ◽

Fura 2 ◽

Pyrethroid Pesticide

Bifenthrin, a commonly used pyrethroid pesticide, evokes various toxicological effects in different models. However, the effect of bifenthrin on cytosolic-free Ca2+ level ([Ca2+] i) and cytotoxicity in human prostate cancer cells is unclear. This study examined whether bifenthrin altered Ca2+ homeostasis and cell viability in PC3 human prostate cancer cells. [Ca2+] i in suspended cells were measured using the fluorescent Ca2+-sensitive dye fura-2. Cell viability was examined by 4-[3-[4-lodophenyl]-2-4(4-nitrophenyl)-2H-5-tetrazolio-1,3-benzene disulfonate] water soluble tetrazolium-1 assay. Bifenthrin (100–400 μM) concentration-dependently induced [Ca2+] i rises. Ca2+ removal reduced the signal by approximately 30%. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) abolished bifenthrin-evoked [Ca2+] i rises. Conversely, treatment with bifenthrin abolished BHQ-evoked [Ca2+] i rises. Inhibition of phospholipase C (PLC) with U73122 significantly inhibited bifenthrin-induced [Ca2+] i rises. Mn2+ has been shown to enter cells through similar mechanisms as Ca2+ but quenches fura-2 fluorescence at all excitation wavelengths. Bifenthrin (400 μM)-induced Mn2+ influx implicates that Ca2+ entry occurred. Bifenthrin-induced Ca2+ entry was inhibited by 30% by protein kinase C (PKC) activator (phorbol 12-myristate 13 acetate) and inhibitor (GF109203X) and three inhibitors of store-operated Ca2+ channels: nifedipine, econazole, and SKF96365. Bifenthrin at 175–275 μM decreased cell viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2-aminophenoxy) ethane- N, N, N′, N′-tetra acetic acid-acetoxymethyl ester. Together, in PC3 cells, bifenthrin-induced [Ca2+] i rises by evoking PLC-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via PKC-sensitive store-operated Ca2+ entry. Bifenthrin also caused Ca2+-independent cell death.

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Plumbagin-Loaded Nanoemulsion Drug Delivery Formulation and Evaluation of Antiproliferative Effect on Prostate Cancer Cells

BioMed Research International ◽

10.1155/2018/9035452 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 8

Author(s):

Adrian Chrastina ◽

Veronique T. Baron ◽

Parisa Abedinpour ◽

Gaelle Rondeau ◽

John Welsh ◽

...

Keyword(s):

Prostate Cancer ◽

Particle Size ◽

Oleic Acid ◽

Particle Size Distribution ◽

Anticancer Activity ◽

Cancer Cells ◽

Size Distribution ◽

Antiproliferative Effect ◽

Prostate Cancer Cells ◽

Kinetics Of

Background. Plumbagin, a medicinal plant-derived 5-hydroxy-2-methyl-1,4-naphthoquinone, is an emerging drug with a variety of pharmacological effects, including potent anticancer activity. We have previously shown that plumbagin improves the efficacy of androgen deprivation therapy (ADT) in prostate cancer and it is now being evaluated in phase I clinical trial. However, the development of formulation of plumbagin as a compound with sparing solubility in water is challenging. Methods. We have formulated plumbagin-loaded nanoemulsion using pneumatically controlled high pressure homogenization of oleic acid dispersions with polyoxyethylene (20) sorbitan monooleate as surfactant. Nanoemulsion formulations were characterized for particle size distribution by dynamic light scattering (DLS). The kinetics of in vitro drug release was determined by equilibrium dialysis. Anticancer activity toward prostate cancer cells PTEN-P2 was assessed by MTS (Owen’s reagent) assay. Results. Particle size distribution of nanoemulsions is tunable and depends on the surfactant concentration. Nanoemulsion formulations of plumbagin with 1-3.5% (w/w) of surfactant showed robust stability of size distribution over time. Plumbagin-loaded nanoemulsion with average hydrodynamic diameter of 135 nm showed exponential release of plumbagin with a half-life of 6.1 h in simulated gastric fluid, 7.0 h in simulated intestinal fluid, and displayed enhanced antiproliferative effect toward prostate cancer cells PTEN-P2 compared to free plumbagin. Conclusion. High drug-loading capacity, retention of nanoparticle size, kinetics of release under simulated physiological conditions, and increased antiproliferative activity indicate that oleic-acid based nanoemulsion formulation is a suitable delivery system of plumbagin.

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COMPARATIVE IN-VITRO ANTICANCER ACTIVITY OF THANGA PARPAM (SIDDHA GOLD DRUG) IN BREAST, LIVER, PROSTATE AND LUNG CANCER CELL LINES

International Journal of Research in Ayurveda and Pharmacy ◽

10.7897/2277-4343.120115 ◽

2021 ◽

Vol 12 (1) ◽

pp. 64-67

Author(s):

Sulthan Shajahan ◽

Arul Amuthan

Keyword(s):

Prostate Cancer ◽

Lung Cancer ◽

Particle Size ◽

Cell Viability ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Prostate Cancer Cells

Thanga parpam is a gold nanoparticle used in Siddha for many chronic and challenging diseases including cancers. Clinically it shows benefit in some cancer types, but not to all types. This study was aimed to compare the in-vitro anticancer activity of Thanga parpam in various cancer cell lines. The particle size and elements were evaluated using Scanning Electron Microscope coupled with Energy Dispersive X-Ray Spectroscopy. Thanga parpam was added to breast adenocarcinoma cells, Human hepatocellular carcinoma cells, Human prostate cancer cells and Human lung adenocarcinoma epithelial cells for 24 hours. MTT assay was used to evaluate the cell viability. Graph was drawn from the % cell viability and dose required to kill 50 % cells was calculated. The gold particles are irregular disk shaped, but agglomerated to each other and not in uniform size. The particle size varies from 17.8 nm – 448 nm. About 9.3% of gold element was present in oxide and sulfide form. It showed dose dependent killing effect on all cancer cell lines. IC50% value was 0.63, 3.51, 6.65 and 11.01 µg/ml for breast, liver, prostate and lung cancer cells respectively. Thanga parpam is a potent anticancer drug to all the four cancer cells, however higher efficacy was observed in breast, liver and prostate cancer cells.

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Water soluble ionic Co(ii), Cu(ii) and Zn(ii) diimine–glycinate complexes targeted to tRNA: structural description, in vitro comparative binding, cleavage and cytotoxic studies towards chemoresistant prostate cancer cells

Dalton Transactions ◽

10.1039/d0dt02657c ◽

2020 ◽

Vol 49 (46) ◽

pp. 16830-16848

Author(s):

Siffeen Zehra ◽

Santiago Gómez-Ruiz ◽

Hifzur R. Siddique ◽

Sartaj Tabassum ◽

Farukh Arjmand

Keyword(s):

Prostate Cancer ◽

Metal Complexes ◽

Cancer Cells ◽

Water Soluble ◽

Cytotoxic Agents ◽

Structural Description ◽

Prostate Cancer Cells ◽

Comparative Binding ◽

Cytotoxic Studies

Four new water soluble Co(ii), Cu(ii) and Zn(ii) ionic metal complexes were synthesized as cytotoxic agents against chemoresistant prostate cancer cells.

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