Melanoma is a malignant tumor that originates in pigment-producing cells called melanocytes. This type of cancer remains a major public health challenge due to its high metastatic potential and resistance to treatment. Autophagy is a catabolic process that enables the controlled degradation of damaged cellular organelles and unnecessary or abnormal macromolecules. Its primary function is to maintain intracellular homeostasis and cell survival. There are three main types of autophagy: macroautophagy, microautophagy and chaperone-mediated autophagy (CMA). The role of autophagy in oncogenesis is multifaceted and context-dependent—depending on the type of cancer and its stage of development. Autophagy can either promote tumor progression or act as a tumor-suppressive mechanism. Factors influencing the role of autophagy in cancer include inflammation, crosstalk with apoptosis and resistance to anticancer therapies. Current research is focused on the use of both autophagy inhibitors and autophagy inducers as potential strategies to improve the effectiveness of melanoma treatment.
Dominika Stencel, D. Wrześniok· International Journal of Mol...· 0 citations
Breast cancer remains one of the leading causes of cancer-related mortality in women worldwide, with estrogen receptor α (ERα) signaling playing a key role in hormone-dependent tumors. Here, we investigated the molecular basis of the anticancer activity of EB171, an amide derivative of betulonic acid, in breast cancer cell lines differing in ERα status (MCF7 and MDA-MB-231). EB171 preferentially reduced viability and proliferation of ERα-positive MCF7 cells, while showing markedly weaker activity in ERα-negative MDA-MB-231 cells, indicating a context-dependent mechanism of action. Mechanistically, EB171 induced replication stress and DNA double-strand breaks, accompanied by activation of cell cycle checkpoints, cyclin suppression, and p21Waf1/Cip1 upregulation. These effects were associated with mitochondrial dysfunction and activation of predominantly intrinsic apoptotic signaling. Importantly, EB171 reduced ERα protein levels in MCF7 cells without significantly affecting ESR1 mRNA expression. This suggests regulation of ERα at a post-transcriptional level, although the underlying mechanism remains to be determined. Notably, the parent compound betulonic acid exerted weaker effects, highlighting the importance of structural modification. Collectively, these findings support further investigation of EB171 as a promising anticancer compound and of the potential contribution of ERα signaling to its biological activity.
Z. Rzepka, Dominika Stencel, E. Bębenek et al.· Toxicology and Applied Pharm...· 0 citations
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