N–3 PUFA dietary supplementation inhibits proliferation and store-operated calcium influx in thymoma cells growing in Balb/c mice

Gabriella Calviello,Paola Palozza,Fiorella Di Nicuolo,Nicola Maggiano,Gianna M Bartoli

doi:10.1016/s0022-2275(20)32050-2

Gabriella Calviello, Paola Palozza + Show 3 more

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https://doi.org/10.1016/s0022-2275(20)32050-2

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Abstract

The antitumor effect of daily individual administration of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (2 g/kg body weight) in Balb/c mice bearing a transplantable thymoma was investigated. Mice received oleic acid (control group), EPA and DHA ethyl esters starting 10 days before tumor inoculation. Analysis of phospholipid composition of neoplastic cell revealed that EPA and DHA levels were significantly increased (63 and 22% increase) after EPA and DHA treatments, respectively. Conversely, decreased levels of arachidonic acid were found in both cases (19 and 24% decrease in EPA and DHA groups, respectively). EPA and DHA delayed the appearance of macroscopic ascites (100% of animal, from 7 to 28 days), prolonged animal survival (100% of animal, from 22 to 32 and 33 days, respectively) and reduced the percentage of proliferating tumor cells detected by immunostaining of proliferation cell nuclear antigen (PCNA) (80 and 85% decrease, respectively). Moreover, the regulatory effects of these dietary n–3 fatty acids on the influx of Ca2+, activated by depletion of intracellular stores with thapsigargin (Tg), were investigated. By using a Ca2+-free/Ca2+-reintroduction protocol and Fura-2 as fluorescent indicator of intracellular free Ca2+([Ca2+]i), we observed that EPA and DHA treatments markedly decreased Tg-induced rise in [Ca2+]i (49 and 37% decrease, respectively). This effect was related to the inhibition of the store-operated Ca2+ influx, as confirmed also by Mn2+ influx experiments. The inhibitory action of EPA and DHA on the store-operated Ca2+ influx could explain, at least in part, their antitumoral activity, as this Ca2+ mobilization pathway appears to be involved in the cell signaling occurring in non-excitable cells to evoke many cellular processes, including cell proliferation. —Calviello, G., P. Palozza, F. Di Nicuolo, N. Maggiano, and G. M. Bartoli. N–3 PUFA dietary supplementation inhibits proliferation and store-operated calcium influx in thymoma cells growing in Balb/c mice.

Highlights

The antitumor effect of daily individual administration of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (2 g/kg body weight) in Balb/c mice bearing a transplantable thymoma was investigated
In this study we found, in agreement with other authors [6,7,8], that the antitumoral action of EPA and DHA was related to the inhibition of cell proliferation and apoptosis
The content of the polyunsaturated fatty acids (PUFAs) was significantly affected by the treatment with the two n –3 fatty acids with respect to the control group

Summary

Introduction

The antitumor effect of daily individual administration of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (2 g/kg body weight) in Balb/c mice bearing a transplantable thymoma was investigated. The regulatory effects of these dietary n–3 fatty acids on the influx of Ca2؉, activated by depletion of intracellular stores with thapsigargin (Tg), were investigated. By using a Ca2؉-free/Ca2؉-reintroduction protocol and Fura-2 as fluorescent indicator of intracellular free Ca2؉([Ca2؉]i), we observed that EPA and DHA treatments markedly decreased Tg-induced rise in [Ca2؉]i (49 and 37% decrease, respectively). This effect was related to the inhibition of the store-operated Ca2؉ influx, as confirmed by Mn2؉ influx experiments. N–3 PUFA dietary supplementation inhibits proliferation and store-operated calcium influx in thymoma cells growing in Balb/c mice.

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