Melatonin and caffeic acid phenethyl ester in the regulation of mitochondrial function and apoptosis: The basis for future medical approaches

Erdemli, Hacı Kemal; Akyol, Sümeyya; Armutçu, Ferah; Güleç, Mehmet Akif; Canbal, Metin; Akyol, Ömer

doi:10.1016/j.lfs.2016.01.026

Cited by 18 publications

(8 citation statements)

References 88 publications

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“…Specifically, we found that higher content of melatonin in the tumor microenvironment was associated with less aggressive stage classification and favorable prognosis, which suggested that the melatonergic microenvironment may influence tumor carcinogenesis, prevent the formation of aggressive phenotypes, and therefore result in a decreased risk of death. This is consistent with previous observations that melatonin reduces the susceptibility of gastric mucosal cells to dietary carcinogens through enhanced DNA repair capacity, and inhibits cancer cell proliferation by decreasing DNA synthesis or promoting cell differentiation . Additionally, we demonstrated that the melatonin synthesis/metabolism Index remained an independent prognosticator after including disease stage for adjustment in multivariable models, which implied that melatonin may influence prognosis through other biological mechanisms in addition to tumor carcinogenesis and proliferation.…”

Section: Discussionsupporting

confidence: 92%

Pan‐cancer genomic analyses reveal prognostic and immunogenic features of the tumor melatonergic microenvironment across 14 solid cancer types

Lv¹,

Zheng²,

Wang³

et al. 2019

Journal of Pineal Research

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We performed comprehensive genomic analyses of the melatonergic system within the tumor microenvironment and their clinical relevance across a broad spectrum of solid tumors. RNA‐seq data from The Cancer Genome Atlas (TCGA) of 14 solid tumors representing 6658 human samples were analyzed. The tumor melatonergic system was characterized by the rates of melatonin synthesis and metabolism using a two‐gene expression model (melatonin synthesis/metabolism Index). We calculated three indexes according to different melatonin metabolism isoenzymes (Index‐I [ASMT:CYP1A1], Index‐II [ASMT:CYP1A2], and Index‐III [ASMT:CYP1B1]). Samples of each cancer type were classified into two subgroups (high vs low) based on median values. Clinical outcomes, mutational burden, and neoepitope abundance were analyzed and compared. We found that the ability of the tumor microenvironment to synthesize and accumulate melatonin varied across cancer types and negatively correlated with tumor burden. Kaplan‐Meier survival analyses and multivariable modeling showed that the three indexes played different roles across different cancers and harbored prognostic values in breast cancer (adjusted hazard ratio [AHR]Index‐II = 0.65 [0.44‐0.97]; P = 0.03), cervical cancer (AHRIndex‐I = 0.62 [0.39‐0.98]; P = 0.04), lung squamous cell carcinoma (AHRIndex‐III = 0.75 [0.56‐0.99]; P = 0.04), melanoma (AHRIndex‐I = 0.74 [0.55‐0.98]; P = 0.04), and stomach adenocarcinoma (AHRIndex‐III = 0.68 [0.41‐0.94]; P = 0.02). We further investigated its clinical relevance with tumor immunogenic features (mutational burden and neoantigen abundance), which may predict immunotherapy benefits. We observed significant negative correlations with mutational burden in the majority of tumors (P < 0.05), except cervical cancer, pancreatic adenocarcinoma, and thyroid carcinoma. Our study provides a systematic overview of the oncostatic values of the melatonergic system and highlights the utilization of this simple and promising gene signature as a prognosticator and potential predictor of response to immunotherapy.

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Section: Discussionsupporting

confidence: 92%

Pan‐cancer genomic analyses reveal prognostic and immunogenic features of the tumor melatonergic microenvironment across 14 solid cancer types

Lv¹,

Zheng²,

Wang³

et al. 2019

Journal of Pineal Research

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“…The latest reports showed that caffeic acid phenethyl ester (CAPE), a functional ingredient isolated from propolis, effectively reduced the number of proinflammatory cytokines and inflammatory mediators by inhibiting the transcription of the nuclear factor κ-light chain inhibitor of activated B cells (NF-κB). Several papers focused on the protective role of CAPE against general tumor models, both in vivo and in vitro for melanomas, lung and prostate cancers [23]. CAPE is a natural phenolic compound and an ester of phenethyl alcohol in the form of caffeic acid.…”

Section: Resultsmentioning

confidence: 99%

The influence of Viburnum opulus polyphenolic compounds on metabolic activity and migration of HeLa and MCF cells

Zakłos‐Szyda

Pawlik

2019

Acta Innovations

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In recent years, research of antitumor activity of natural compounds isolated from plant material has increased. Polyphenols have gained significant attention due to their proapoptotic abilities and their involvement in migration and inhibition of metastasis processes. The anticancer effects of polyphenolic extracts of Viburnum opulus fruit against human breast (MCF-7) and cervical (HeLa) cancer cell lines have been confirmed in this study. It was demonstrated that the tested preparations (methanol – M and acetone – A from pomace, juice – J and juice after extraction to the solid phase SPE – PF) show cytotoxic activity and regulate the migration process of cancer cells. The degree of inhibition of cell migration was measured at two times - 24 h and 48 h after addition of the tested preparations. The highest toxicity towards both cell lines was demonstrated by the polyphenol fraction obtained after juice purification SPE (IC50 values at concentration of 63,541 and 19,380 μg/mL for HeLa and MCF cell lines, respectively). At the same time, the same preparation inhibited cell migration the most (nearly 70% compared to controls at both times at the concertation of 15 and 30 μg/mL). All preparations showed the antioxidant ability, but the Viburnum opulus juice (200 and 350 g/mL) and the preparation after its purification (15 and 30 μg/mL) have larger ability to inhibit the intracellular oxidative stress (30-40%) than preparation obtained from pomace (nearly by 20% at concentration of 20 and 50 μg/mL of M and A). Despite the antioxidative capacity of the preparations, they simultaneously decreased cellular mitochondrial potential. The results obtained indicate the high potential of components of Viburnum opulus polyphenolic compounds can be used in the production of innovative dietary supplements or pharmacological preparations for people with an increased risk or inclination towards developing breast or cervical cancer.

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“…Caffeic acid phenethyl ester (CAPE), extracted from propolis, exhibits most bioactive activity among other substances . CAPE has been shown to possess a broad spectrum of biological activities including anti‐oxidant, anti‐inflammatory, and anti‐tumor properties . About cancer cells, CAPE has been shown to be able to repress a myriad of cancer cells growth, such as breast cancer, prostate cancer, lung cancer, etc.…”

Section: Introductionmentioning

confidence: 99%

Caffeic acid phenethyl ester upregulates N-myc downstream regulated gene 1 via ERK pathway to inhibit human oral cancer cell growth in vitro and in vivo

Chung

Chiang

Feng

et al. 2017

Mol. Nutr. Food Res.

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Melatonin and caffeic acid phenethyl ester in the regulation of mitochondrial function and apoptosis: The basis for future medical approaches

Cited by 18 publications

References 88 publications

Pan‐cancer genomic analyses reveal prognostic and immunogenic features of the tumor melatonergic microenvironment across 14 solid cancer types

Pan‐cancer genomic analyses reveal prognostic and immunogenic features of the tumor melatonergic microenvironment across 14 solid cancer types

The influence of Viburnum opulus polyphenolic compounds on metabolic activity and migration of HeLa and MCF cells

Caffeic acid phenethyl ester upregulates N-myc downstream regulated gene 1 via ERK pathway to inhibit human oral cancer cell growth in vitro and in vivo

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