TY - JOUR
T1 - The proteomic landscape of ovarian cancer cells in response to melatonin
AU - Cesário, Roberta Carvalho
AU - Gaiotte, Leticia Barbosa
AU - Cucielo, Maira Smaniotto
AU - Silveira, Henrique Spaulonci
AU - Delazari dos Santos, Lucilene
AU - de Campos Zuccari, Debora Aparecida Pires
AU - Seiva, Fábio Rodrigues Ferreira
AU - Reiter, Russel J.
AU - de Almeida Chuffa, Luiz Gustavo
N1 - Funding Information:
We are grateful to Fundação de Amparo à Pesquisa do Estado de São Paulo , FAPESP (Grant number 2019/00906-6 ), CAPES ( 88887.482368/2020-00 ), and the National Council for Scientific and Technological Development , CNPq (Process 304108/2020-0 ) for providing financial support. We are thankful to the Institute of Biotechnology (IBTEC-UNESP) and to Luiz Antonio Lupi for the proteomics analyses of this study.
Funding Information:
We are grateful to Funda??o de Amparo ? Pesquisa do Estado de S?o Paulo, FAPESP (Grant number 2019/00906-6), CAPES (88887.482368/2020-00), and the National Council for Scientific and Technological Development, CNPq (Process 304108/2020-0) for providing financial support. We are thankful to the Institute of Biotechnology (IBTEC-UNESP) and to Luiz Antonio Lupi for the proteomics analyses of this study.
Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - Ovarian cancer (OC) is the most lethal gynecological malignancy with a highly negative prognosis. Melatonin is an indoleamine secreted by the pineal gland during darkness and has shown antitumor activity in both in vitro and in vivo experiments. Herein, we investigated the influence of melatonin on the proteome of human ovarian carcinoma cells (SKOV-3 cell line) using the Ultimate 3000 LC Liquid NanoChromatography equipment coupled to a Q-Exactive mass spectrometry. After 48 h of treatment, melatonin induced a significant cytotoxicity especially with the highest melatonin concentration. The proteomic profile revealed 639 proteins in the control group, and 98, 110, and 128 proteins were altered by melatonin at the doses of 0.8, 1.6, and 2.4 mM, respectively. Proteins associated with the immune system and tricarboxylic acid cycle were increased in the three melatonin-exposed groups of cells. Specifically, the dose of 2.4 mM led to a reduction in molecules associated with protein synthesis, especially those of the ribosomal protein family. We also identified 28 potential genes shared between normal ovarian tissue and OC in all experimental groups, and melatonin was predicted to alter genes encoding ribosomal proteins. Notably, the set of proteins changed by melatonin was linked to a better prognosis for OC patients. We conclude that melatonin significantly alters the proteome of SKOV-3 cells by changing proteins involved with the immune response and mitochondrial metabolism. The concentration of 2.4 mM of melatonin promoted the largest number of protein changes. The evidence suggests that melatonin may be an effective therapeutic strategy against OC.
AB - Ovarian cancer (OC) is the most lethal gynecological malignancy with a highly negative prognosis. Melatonin is an indoleamine secreted by the pineal gland during darkness and has shown antitumor activity in both in vitro and in vivo experiments. Herein, we investigated the influence of melatonin on the proteome of human ovarian carcinoma cells (SKOV-3 cell line) using the Ultimate 3000 LC Liquid NanoChromatography equipment coupled to a Q-Exactive mass spectrometry. After 48 h of treatment, melatonin induced a significant cytotoxicity especially with the highest melatonin concentration. The proteomic profile revealed 639 proteins in the control group, and 98, 110, and 128 proteins were altered by melatonin at the doses of 0.8, 1.6, and 2.4 mM, respectively. Proteins associated with the immune system and tricarboxylic acid cycle were increased in the three melatonin-exposed groups of cells. Specifically, the dose of 2.4 mM led to a reduction in molecules associated with protein synthesis, especially those of the ribosomal protein family. We also identified 28 potential genes shared between normal ovarian tissue and OC in all experimental groups, and melatonin was predicted to alter genes encoding ribosomal proteins. Notably, the set of proteins changed by melatonin was linked to a better prognosis for OC patients. We conclude that melatonin significantly alters the proteome of SKOV-3 cells by changing proteins involved with the immune response and mitochondrial metabolism. The concentration of 2.4 mM of melatonin promoted the largest number of protein changes. The evidence suggests that melatonin may be an effective therapeutic strategy against OC.
KW - Immune response
KW - Melatonin
KW - Mitochondrial metabolism
KW - Ovarian cancer
KW - Proteome
KW - SKOV-3 cells
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U2 - 10.1016/j.lfs.2022.120352
DO - 10.1016/j.lfs.2022.120352
M3 - Article
C2 - 35074409
AN - SCOPUS:85123980625
SN - 0024-3205
VL - 294
JO - Life Sciences
JF - Life Sciences
M1 - 120352
ER -