Octyl and dodecyl gallates induce oxidative stress and apoptosis in a melanoma cell line

Abstract

This study investigated the mechanism of cytotoxicity of octyl (G8) and dodecyl (G12) gallates in a murine melanoma cell line (B16F10). For this purpose, several methods to measure cell viability were used to determine if the cytotoxicity induced by these gallates corresponds to a general or an organelle-specific effect. Furthermore, the mechanisms related to apoptosis were examined, by studying the caspase-3 activity, oxidative stress, mitochondrial potential and the expression of anti- or proapoptotic proteins. When comparing the various methods of assessing cell viability, the tested gallates showed a higher cytotoxicity in the assay that indicates lysosomal activity, compared with the assays that indicate mitochondrial and ribosomal activities. Both gallates promoted the release of lactate dehydrogenase into the medium, indicating an effect on cell membrane integrity. The gallates also promoted cellular oxidative stress, mitochondrial depolarization and an increase in caspase-3 activity. Furthermore, the gallates induced an increase in proapoptotic (Bax) and a decrease in antiapoptotic (Bcl-2) proteins expression. Our results indicate that the apoptotic cell death induced by G8 and G12 in B16F10 cells involves lipid membrane damages, lysosomal and mitochondrial dysfunction, which was accompanied by alterations in apoptotic proteins expression and seems to be triggered by cellular oxidative stress.

Entropy‐driven binding of octyl gallate in albumin: Failure in the application of temperature effect to distinguish dynamic and static fluorescence quenching

“…G8 is applied in the food, pharmaceutical, and cosmetic industries due to its antioxidant properties . Its alkyl chain contributes to the increased lipophilicity, affinity, and permeability through the cell plasma membranes . This property has been explored in its antitumor effect on B‐cell leukemia, melanoma, and lymphoma .…”

Gallic Acid and Dodecyl Gallate Prevents Carbon Tetrachloride-Induced Acute and Chronic Hepatotoxicity by Enhancing Hepatic Antioxidant Status and Increasing p53 Expression

“…10,13,[45][46][47] The results of this study suggest that GA and DGA present a hepatoprotective effect against the toxic action promoted by CCl 4 . The results of Table 5 indicate that the effect of GA seems to be dose dependent, while the effect of the DGA is dose-independent.…”

“…However, they show changes in these markers when given in animals with tumors or in tumor cells. 10,13,[45][46][47] These results lead us to believe that gallic acid and its derivatives selectively act on damaged cells and tissues.…”

“…Our results corroborate with several studies showing that GA and its esters are capable of promoting apoptosis increasing caspase 3 and Bax in tumor cells without causing significant damage to normal cells. 13,46) Also, they presented antioxidant activity by inhibiting ROS production as well as scavenging them. 14,56) In this way we understand that the increase in p53 gene expression induced by gallic acid and dodecyl gallate is related to the antioxidant status and not to the apoptotic events, since these compounds present high antioxidant power.…”

Octyl Gallate Induces Pancreatic Ductal Adenocarcinoma Cell Apoptosis and Suppresses Endothelial-Mesenchymal Transition-Promoted M2-Macrophages, HSP90α Secretion, and Tumor Growth

“…Several studies have reported the chemopreventive and anti-carcinogenic effects of gallic acid and its derivatives in animal tumors or human cancer cell lines [12][13][14]. OG induced apoptosis in tumor cells and showed an anti-proliferative effect on melanoma cells [15]. A recent study also showed that OG induced mitochondrial-mediated apoptosis in the hepatocellular carcinoma cell line [16].…”