Luiz Gustavo de Almeida Chuffa

Melatonin changes energy metabolism and reduces oncogenic signaling in ovarian cancer cells

Ovarian cancer (OC) adjusts energy metabolism in favor of its progression and dissemination. Because melatonin (Mel) has antitumor actions, we investigated its impact on energy metabolism and kinase signaling in OC cells (SKOV-3 and CAISMOV-24). Cells were divided into control and Mel-treated groups, in the presence or absence of the antagonist luzindole. There was a decrease in the levels of HIF-1α, G6PDH, GAPDH, PDH, and CS after Mel treatment even in the presence of luzindole in both OC cells. Mel treatment also reduced the activity of OC-related enzymes including PFK-1, G6PDH, LDH, CS, and GS whereas PDH activity was increased. Lactate and glutamine levels dropped after Mel treatment. Mel further promoted a reduction in the concentrations of CREB, JNK, NF-kB, p-38, ERK1/2, AKT, P70S6K, and STAT in both cell lines. Mel reverses Warburg-type metabolism and possibly reduces glutaminolysis, thereby attenuating various oncogenic molecules associated with OC progression and invasion.

Transcriptomic landscape of male and female reproductive cancers: Similar pathways and molecular signatures predicting response to endocrine therapy

Reproductive cancers in both genders represent serious health problems, whose incidence has significantly risen over the past decades. Although considerable differences among reproductive cancers exist, we aimed to identify similar signaling pathways and key molecular oncomarkers shared among six human reproductive cancers that can advance the current knowledge of cancer biology to propose new strategies for more effective therapies. Using a computational analysis approach, here we uncover aberrant miRNAs-mRNAs networks shared in six reproductive tumor types, and identify common molecular mechanisms strictly associated with cancer promotion and aggressiveness. Based on the fact that estrogenic and androgenic signaling pathways were most active in prostate and breast cancers, we further demonstrated that both androgen and estrogen deprivation therapy are capable of regulating the expression of the same key molecular sensors associated with endoplasmic reticulum dysfunction and cell cycle in these cancers. Overall, our data reveal a potential mechanistic framework of cellular processes that are shared among reproductive cancers, and particularly, highlight the importance of hormonal deprivation in breast and prostate cancers and potentially new biomarkers of response to these therapeutic approaches.