TY - JOUR
T1 - Melatonin changes energy metabolism and reduces oncogenic signaling in ovarian cancer cells
AU - Silveira, Henrique Spaulonci
AU - Cesário, Roberta Carvalho
AU - Vígaro, Renan Aparecido
AU - Gaiotte, Leticia Barbosa
AU - Cucielo, Maira Smaniotto
AU - Guimarães, Fernando
AU - Seiva, Fábio Rodrigues Ferreira
AU - Zuccari, Debora Aparecida P.C.
AU - Reiter, Russel J.
AU - Chuffa, Luiz Gustavo de Almeida
N1 - Publisher Copyright:
© 2024 Elsevier B.V.
PY - 2024/10/1
Y1 - 2024/10/1
N2 - 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.
AB - 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.
KW - Cellular metabolism
KW - Glutaminolysis
KW - Kinase signaling
KW - Melatonin
KW - Ovarian cancer
KW - Tumor progression
KW - Warburg effect
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UR - http://www.scopus.com/inward/citedby.url?scp=85195310374&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2024.112296
DO - 10.1016/j.mce.2024.112296
M3 - Article
C2 - 38844096
AN - SCOPUS:85195310374
SN - 0303-7207
VL - 592
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
M1 - 112296
ER -