Effect of betaine, C-phycocyanin or physical activity on tumour growth of lung cancer in rats
Résumé
Oxidative stress seems to play a crucial role as a secondary messenger in the regulation of several cellular processes such as apoptosis, survival and proliferation, and could be involved in all steps of the lung carcinogenesis (i.e.initiation, promotion and progression). Physical activity and nutrition are two factors able to modulate oxidative stress and associated mechanisms. Betaine and C-phycocyanin are two known micronutrients having antioxidant, anti-inflammatory
and anti-proliferative effects. Previously, our team showed that betaine and/or C-phycocyanin treatment decreased the viability of A549 cells in vitro (pulmonary adenocarcinoma cell line).
The main objective of this work was to evaluate the effect of nutritional factors (betaine, C-phycocyanin or physical activity) on growth of implanted A549 cells in Nude rats and to determine underlying mechanisms. Firstly, we showed that these two micronutrients, whether associated or supplied separately, slowed down the lung tumour growth through similar mechanisms (NF-B activation and increase of lipid peroxidation and expression of proinflammatory cytokines (IL-1, Cox-2 et TNF-) in tumour). Also, some mechanisms were specific for each micronutrient or their combination. C-phycocyanin induced a decrease of phosphorylated AKT / total AKT ratio, and an increase of phosphorylated p38 / total p38 ratio, both mechanisms promoting apoptosis and autophagy. On the other hand, betaine associated with C-phycocyanin increased caspase-3 / pro-caspase-3 ratio. Secondly, we studied the effect of voluntary physical activity on growth of implanted A549 cells in Nude rats. We showed that voluntary physical activity slowed down the lung tumour growth, without significant difference if animals were supplied with betaine or/and C-phycocyanin. It seems that the increase of lipid peroxidation, NF-B and p38 activation, and AKT inhibition, all having a role in promotion of a cell death, are responsible for the tumour growth slowdown following
the physical activity. Diet enriched with betaine or/and C-phycocyanin slows down the growth of pulmonary adenocarcinoma cells implanted in rats, suggesting their interest in anti-cancer activity. Physical activity seems to act on similar mechanisms as these micronutrients. Our results have to be confirmed with further studies, but are already suggesting a potential application in lung cancer patients