Melatonin Inhibits EMT in Bladder Cancer by Targeting Autophagy

Hsiao, Sheng-Yen; Tang, Chih‐Hsin; Chen, Po-Chun; Lin, Tien‐Huang; Chao, Chia‐Chia

doi:10.3390/molecules27248649

Cited by 9 publications

(3 citation statements)

References 57 publications

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“…Ehteda et al found that the combination of ALB with 2-methoxyestradiol synergizes the induction of apoptosis of colon cancer cells and improves the survival of HCT-116 tumor-bearing nude mice [ 47 ]. The synergy was based on the sum effect of microtubule-binding activity of both drugs, which differs from our approach, which is based on the possible sum of the different mechanisms of action attributed to ALB and MLT, as mentioned above [ 17 , 18 , 24 , 27 ]. On the other hand, MLT also has shown a chemosensitizing effect, since MLT downregulates the expression of ABC transporter ABCG2, inducing the synergistic cytotoxicity when combined with TMZ against GB cells and GB-stem cells [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…MLT is a highly lipophilic molecule that can diffuse through the cell membrane to interact with intracellular targets [ 22 ]. Several studies have shown the potential use of MLT in the treatment of cancer [ 23 ], including GB, with synergistic activity when combined with other drugs, attributed to the inhibition of multiple pro-survival pathways, the inhibition of efflux pumps, and the regulation of autophagy [ 24 , 25 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Melatonin in Combination with Albendazole or Albendazole Sulfoxide Produces a Synergistic Cytotoxicity against Malignant Glioma Cells through Autophagy and Apoptosis

et al. 2023

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Glioblastoma is the most aggressive and lethal brain tumor in adults, presenting diffuse brain infiltration, necrosis, and drug resistance. Although new drugs have been approved for recurrent patients, the median survival rate is two years; therefore, new alternatives to treat these patients are required. Previous studies have reported the anticancer activity of albendazole, its active metabolite albendazole sulfoxide, and melatonin; therefore, the present study was performed to evaluate if the combination of melatonin with albendazole or with albendazole sulfoxide induces an additive or synergistic cytotoxic effect on C6 and RG2 rat glioma cells, as well as on U87 human glioblastoma cells. Drug interaction was determined by the Chou–Talalay method. We evaluated the mechanism of cell death by flow cytometry, immunofluorescence, and crystal violet staining. The cytotoxicity of the combinations was mainly synergistic. The combined treatments induced significantly more apoptotic and autophagic cell death on the glioma cell lines. Additionally, albendazole and albendazole sulfoxide inhibited proliferation independently of melatonin. Our data justify continuing with the evaluation of this proposal since the combinations could be a potential strategy to aid in the treatment of glioblastoma.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Melatonin in Combination with Albendazole or Albendazole Sulfoxide Produces a Synergistic Cytotoxicity against Malignant Glioma Cells through Autophagy and Apoptosis

et al. 2023

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“…MlT has a variety of physiological effects such as regulating the circadian rhythm, promoting sleep, enhancing immunity and scavenging free radicals, as well as anti-oxidation and anti-stress properties. MlT also displays antitumor activity including anti-proliferation, pro-apoptosis and anti-metastasis (10,11). Based on the fact that MlT effectively inhibits a variety of tumors, it has been used in combination with chemotherapy drugs to enhance the sensitivity of tumor cells to chemotherapy and inhibit tumor drug resistance.…”

Section: Introductionmentioning

confidence: 99%

Loss of keratin 23 enhances growth inhibitory effect of melatonin in gastric cancer

Li,

Lin,

Luo

et al. 2023

Mol Med Rep

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To investigate the effect of keratin 23 (KrT23) on the anticancer activity of melatonin (MlT) against gastric cancer (Gc) cells, microarray analysis was applied to screen differentially expressed genes in aGS Gc cells following MlT treatment. Western blotting was used to detect the expression of KrT23 in Gc cells and normal gastric epithelial cell line GeS-1. KrT23 knockout was achieved by criSPr/cas9. assays of cell viability, colony formation, cell cycle, electric cell-substrate impedance sensing and western blotting were conducted to reveal the biological functions of KrT23-knockout cells without or with MlT treatment. Genes downregulated by MlT were enriched in purine metabolism, pyrimidine metabolism, genetic information processing and cell cycle pathway. expression levels of KrT23 were downregulated by MlT treatment. expression levels of KrT23 in aGS and Snu-216 Gc cell lines were significantly higher compared with normal gastric epithelial cell line GeS-1. KrT23 knockout led to reduced phosphorylation of erK1/2 and p38, arrest of the cell cycle and inhibition of Gc cell proliferation. Moreover, KrT23 knockout further enhanced the inhibitory activity of MlT on the tumor cell proliferation by inhibiting the phosphorylation of p38/erK. KrT23 knockout contributes to the antitumor effects of MlT in Gc via suppressing p38/erK phosphorylation. in the future, KrT23 might be a potential prognostic biomarker and a novel molecular target for Gc.

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