Combination of melatonin with paclitaxel reduces the TLR4-mediated inflammatory pathway, PD-L1 levels, and survival of ovarian carcinoma cells

Melatonin and paclitaxel in the OC cell

  • Leticia B Gaiotte Department of Structural and Functional Biology, Institute of Biosciences, UNESP - Sao Paulo State University, Botucatu 18618-689, São Paulo, Brazil
  • Roberta C Cesário Department of Structural and Functional Biology, Institute of Biosciences, UNESP - Sao Paulo State University, Botucatu 18618-689, São Paulo, Brazil
  • Henrique S Silveira Department of Structural and Functional Biology, Institute of Biosciences, UNESP - Sao Paulo State University, Botucatu 18618-689, São Paulo, Brazil
  • Diego Augusto de Morais Oliveira Department of Structural and Functional Biology, Institute of Biosciences, UNESP - Sao Paulo State University, Botucatu 18618-689, São Paulo, Brazil
  • Maira S Cucielo Department of Structural and Functional Biology, Institute of Biosciences, UNESP - Sao Paulo State University, Botucatu 18618-689, São Paulo, Brazil
  • Graziela G Romagnoli Department of Chemical and Biological Sciences, Institute of Biosciences, UNESP - São Paulo State University, Botucatu 18618-689, São Paulo, Brazil
  • Ramon Kaneno Department of Chemical and Biological Sciences, Institute of Biosciences, UNESP - São Paulo State University, Botucatu 18618-689, São Paulo, Brazil
  • Debora Aparecida P de Campos Zuccari Faculty of Medicine of São José do Rio Preto, São José do Rio Preto 15090-000, São Paulo, Brazil
  • Russel J Reiter Department of Cell Systems and Anatomy, UT Health, San Antonio, TX 782229, USA
  • Luiz Gustavo de Almeida Chuffa Department of Structural and Functional Biology, Institute of Biosciences, UNESP - Sao Paulo State University, Botucatu 18618-689, São Paulo, Brazil
DOI: https://doi.org/10.32794/mr112500118
Keywords: Ovarian cancer, melatonin, paclitaxel, Toll-like receptor, PD-L1, cell signaling, SKOV-3 cells

Abstract

Ovarian cancer (OC) has a high mortality rate. Although most patients respond to the conventional chemotherapy [e.g., paclitaxel (PTX)], some also develop drug resistance to make the treatment less effective. Since melatonin exhibits antioxidant, antitumor, and immunomodulatory functions in a variety of solid tumors, in this study the effects of a combination of PTX and melatonin on SKOV-3 human ovarian carcinoma cells were investigated and the focus was given to the Toll-like receptor (TLR)-mediated inflammatory pathway and cell signaling-related molecules. Flow cytometry showed that this combination significantly boosted the apoptosis/necrosis responses of the cancer cells. Cell migration was attenuated by melatonin alone, and the combination led to a reduced number of migrating and invasive cells. Melatonin alone and its combination also reduced the levels of TLR4, MyD88, TRIF, and PD-L1, but not TLR2. In addition, the combination significantly lowered the levels of NF-kB p65, PI3K, p-AKT, p38, ERK 1/2, JNK, CREB, p70s6K, and STAT5. The results suggested that this combination was effective in reducing the viability and the invasive capacity of SKOV-3 cells while increasing their apoptosis and necrosis rates. The potential mechanism of this combination is to attenuate the downstream molecules of the TLR4-mediated inflammatory pathway and cell signaling-related proteins in the cancer cells. Thus, melatonin improved the chemosensitivity of the cancer cells to PTX, serving as an effective adjuvant therapy against OC.


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Published
2022-03-23
How to Cite
[1]
Gaiotte, L.B., Cesário, R.C., Silveira, H.S., de Morais Oliveira, D.A., Cucielo, M.S., Romagnoli, G.G., Kaneno, R., de Campos Zuccari, D.A.P., Reiter, R.J. and Chuffa, L.G. de A. 2022. Combination of melatonin with paclitaxel reduces the TLR4-mediated inflammatory pathway, PD-L1 levels, and survival of ovarian carcinoma cells. Melatonin Research. 5, 1 (Mar. 2022), 34-51. DOI:https://doi.org/https://doi.org/10.32794/mr112500118.
Issue
Vol 5 No 1 (2022): Melatonin Research
Section
Research Articles
DOI
https://doi.org/10.32794/mr112500118
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