Polyphenolic Antioxidants Mimic the Effects of 1,4-Dihydropyridines on Neurotensin Receptor Function in PC3 Cells

Abstract

This study aimed to determine the mechanism(s) by which 1,4-dihydropyridine Ca 2ϩ channel blockers (DHPs) enhance the binding of neurotensin (NT) to prostate cancer PC3 cells and inhibit NT-induced inositol phosphate formation. Earlier work indicated that these effects, which involved the G proteincoupled NT receptor NTR1, were indirect and required cellular metabolism or architecture. At the micromolar concentrations used, DHPs can block voltage-sensitive and store-operated Ca 2ϩ channels, K ϩ channels, and Na ϩ channels, and can inhibit lipid peroxidation. and [Na ϩ ], we showed that these ions did not contribute to either effect. For a series of DHPs, the activity order for effects on NTR1 function followed that for antioxidant ability. Antioxidant polyphenols (luteolin and resveratrol) mimicked the effects of DHPs and showed structural similarity to DHPs. Antioxidants with equal redox ability, but without structural similarity to DHPs (such as ␣-tocopherol, riboflavin, and N-acetyl-cysteine) were without effect. A flavoprotein oxidase inhibitor (diphenylene iodonium) and a hydroxy radical scavenger (butylated hydroxy anisole) also displayed the effects of DHPs. In conclusion, DHPs indirectly alter NTR1 function in live cells by a mechanism that depends on the drug's ability to donate hydrogen but does not simply involve sulfhydryl reduction.

A microfluidic‐based system for analysis of single cells based on Ca2+ flux

“…Since it is of interest to investigate the effect from different stimuli simultaneously or in a given sequence [45][46][47], the proposed microfluidic-based system could provide the possibility to apply different stimulation test solutions to a selected area of cells in a controllable manner, i.e., simultaneously or as a series of plugs in a given sequence without mechanically disturbing cells. Future studies will investigate both (i) the historical effects of having previously exposed the cell to other agonists, on any given response, being measured; and (ii) longer term effects due to the mechanical effects of flow (shear-stress) on stretch receptors within the CHO cell.…”

“…It can be seen that both curves show a similar trend, except that the UTP gave a stronger stimulation than ionomycin. It has been reported that UTP could induce calcium flux responses similar to ionomycin [45] although the cellular reaction mechanism was thought to be different [46].…”

Safrole-Induced Ca2+Mobilization and Cytotoxicity in Human PC3 Prostate Cancer Cells

“…One characteristic of the safrole-induced Ca 2+ entry is its insensitivity to voltage-gated Ca 2+ entry blockers. In PC3 cells, micromolar concentrations of dihydropyridines have been shown to block voltage-sensitive and store-operated Ca 2+ channels (35).…”

The Emerging Therapy of Tomorrow with Nanomedicine: Present Status

“…To increase the efficacy of anticancer drug and to reduce the toxic effect, a polymeric misceller and liposome based delivery system conjugated to tumor specific ligands have been studied 51 , 52 , 53 . In prostatic tumor -the tumor cell overexpress transferring receptor and for targeting drug to tumor, ligand transferring has been investigated 54 . For the treatment of a localize prostatic tumor the approach is direct intertumoral delivery of biodegradable nanoparticles, a controlled release formulation, providing sustained drug effect 55 .…”