Tamoxifen alters lysosomes of breast cancer cells by a mechanism independent of its anti-estrogenic activity

PEREIRA LAURA; GUARNIOLO D; CHAPANA A; SOSA MA; CARVELLI L,

Congreso; XXXVI Scientific Meeting of the Cuyo Biology Society; 2018

Sociedad de Biología de Cuyo

Breast cancer is one of the most important causes of morbidity and mortality worldwide. It has been shown that the cells of some tumors have an increased lysosomal biogenesis in response to metabolic alterations, which also has an impact on the integrity and / or lysosomal functionality, showing increased levels of lysosomal proteases, such as cathepsin D ( Cat D). It has been shown that this enzyme induces apoptosis when is released into the cytoplasm. Since the lysosomes may play a role either as initiators or executors of apoptotic processes when the membrane integrity is altered, this organelle could be taken as a potential therapeutic target against tumors. The aim of this study was to evaluate the effect of estrogens and tamoxifen on lysosomal proteins ofin breast cancer cells. The MCF7 cell line (positive to estrogen receptor REα), showed that CatD is positively regulated by 17-β-estradiol, while in the MDA-MB231 cell line (tumorigenic non-expressing REα) the enzyme is constitutively overexpressed. Tamoxifen (TAM) is one of the most commonanti-estrogenic drugs used in breast cancer therapy . This binds to the ER and inhibits transcriptional activity in the mammary gland. As expected, TAM blocked the effect of estrogen on MCF7 cells. However, TAM also altered Cat D processing and decreased the number of acidic lysosomes (lysotracker positive) in both cell lines when used alone. Neither effect of TAM was observed on MCF-10A (non-tumorigenic) . In addition, a decrease of the lysosomal protein GM2AP ( related to the development of tumors) was observed in the cells due to TAM. All these results suggest that TAM has additional effects independent on estrogenic activity, possible due to lysosomotropic action.