RT Journal Article
T1 Melatonin downregulates TRPC6, impairing store-operated calcium entry in triple-negative breast cancer cells
A1 Jardin, Isaac
A1 Diez-Bello, Raquel
A1 Falcon, Debora
A1 Alvarado, Sandra
A1 Regodon, Sergio
A1 Salido, Gines M.
A1 Smani, Tarik
A1 Rosado, Juan A.
K1 Induced oxidative stress
K1 Expression
K1 Hippocampus
K1 Modulation
K1 Apoptosis
K1 Channels
K1 Trpm2
AB Melatonin has been reported to induce effective reduction in growth and development in a variety of tumors, including breast cancer. In triple-negative breast cancer (TNBC) cells, melatonin attenuates a variety of cancer features, such as tumor growth and apoptosis resistance, through a number of still poorly characterized mechanisms. One biological process that is important for TNBC cells is store-operated Ca2+ entry (SOCE), which is modulated by TRPC6 expression and function. We wondered whether melatonin might intersect with this pathway as part of its anticancer activity. We show that melatonin, in the nanomolar range, significantly attenuates TNBC MDA-MB-231 cell viability, proliferation, and migration in a time- and concentration-dependent manner, without having any effect on nontumoral breast epithelial MCF10A cells. Pretreatment with different concentrations of melatonin significantly reduced SOCE in MDA-MB-231 cells without altering Ca2+ release from the intracellular stores. By contrast, SOCE in MCF10A cells was unaffected by melatonin. In the TNBC MDA-MB-468 cell line, melatonin not only attenuated viability, migration, and SOCE, but also reduced TRPC6 expression in a time- and concentration-dependent manner, without altering expression or function of the Ca2+ channel Orai1. The expression of exogenous TRPC6 overcame the effect of melatonin on SOCE and cell proliferation, and silencing or inhibition of TRPC6 impaired the inhibitory effect of melatonin on SOCE. These findings indicate that TRPC6 downregulation might be involved in melatonin's inhibitory effects on Ca2+ influx and the maintenance of cancer hallmarks and point toward a novel antitumoral mechanism of melatonin in TNBC cells.
PB Elsevier
YR 2021
FD 2021-01
LK http://hdl.handle.net/10668/18924
UL http://hdl.handle.net/10668/18924
LA en
NO Jardin I, Diez-Bello R, Falcon D, Alvarado S, Regodon S, Salido GM,et al. Melatonin downregulates TRPC6, impairing store-operated calcium entry in triple-negative breast cancer cells. J Biol Chem. 2021 Jan-Jun;296:100254.
DS RISalud
RD Jul 29, 2025