ABSTRACT
The current standard of care for colon cancer surveillance relies heavily on white light endoscopy (WLE). However, dysplastic lesions that are not visible to the naked eye are often missed when conventional WLE equipment is used. Although dye-based chromoendoscopy shows promise, current dyes cannot delineate tumor tissues from surrounding healthy tissues accurately. The goal of the present study was to screen various phthalocyanine (PC) dye-loaded micelles for their ability to improve the direct visualization of tumor tissues under white light following intravenous administration. Zinc PC (tetra-tert-butyl)-loaded micelles were identified as the optimal formulation. Their accumulation within syngeneic breast tumors led the tumors to turn dark blue in color, making them clearly visible to the naked eye. These micelles were similarly able to turn spontaneous colorectal adenomas in Apc+/Min mice a dark blue color for easy identification and could enable clinicians to more effectively detect and remove colonic polyps.
Subject(s)
Neoplasms , Nanoparticles/chemistry , Neoplasms/diagnostic imaging , Light , Coloring Agents/chemistry , Micelles , Male , Animals , Mice , Humans , Mice, Inbred BALB C , Cell Line, TumorABSTRACT
OBJECTIVES: The effects of propolis and phenolic compounds (caffeic acid - Caf; dihydrocinnamic acid - Cin; p-coumaric acid - Cou) in the same quantity found in our propolis sample were investigated on human laryngeal epidermoid carcinoma (HEp-2) cells. METHODS: Cell viability, apoptosis/necrosis and cell cycle arrest, P53 and CASPASE-3 gene expression, generation of reactive oxygen species (ROS) and the ability of propolis to induce doxorubicin (DOX) efflux using a P-glycoprotein (P-gp) inhibitor (verapamil) were assayed. KEY FINDINGS: Propolis exerted a cytotoxic effect on HEp-2 cells, whereas isolated compounds had no effect on cell viability. Higher concentrations were tested and Caf induced late apoptosis or necrosis in HEp-2 cells, while propolis induced apoptosis, both probably due to ROS generation. P53 expression was downregulated by propolis but not by Caf. CASPASE-3 expression was correlated with induction of both early and late apoptosis, with both propolis and Caf alone upregulating its expression. Propolis induced cell cycle arrest at G2/M phase and Caf at S phase. Propolis but not Caf may act as a P-gp inhibitor by modulating P-gp activity and inhibiting DOX efflux. CONCLUSIONS: Propolis exerted cytotoxic effects on HEp-2 cells, and the mechanisms are discussed, showing its potential as an antitumour drug.