Gallic acid inhibits the growth of HeLa cervical cancer cells via apoptosis and/or necrosis

• Published in: Food and chemical toxicology Vol. 48; no. 5; pp. 1334 - 1340
• Main Authors: You, Bo Ra, Moon, Hwa Jin, Han, Yong Hwan, Park, Woo Hyun
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-05-2010; Elsevier
• Subjects: acid treatment; Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Caspase; cell culture; Cell Survival - drug effects; cytotoxicity; Drug Screening Assays, Antitumor; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; enzyme inhibition; enzyme inhibitors; Female; Female genital diseases; Gallic acid; Gallic Acid - pharmacology; Glutathione - metabolism; GSH; Gynecology. Andrology. Obstetrics; HeLa Cells; human cell lines; Humans; Medical sciences; Membrane Potential, Mitochondrial - drug effects; necrosis; Necrosis - chemically induced; reactive oxygen species; ROS; Superoxides - metabolism; Toxicology; Tumors; umbilical cord; Umbilical Veins - cytology; uterine cervical neoplasms; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology; DHE; Gallic acid; H 2DCFDA; Z-VAD-FMK; Caspase; MTT; CMFDA; Z-LEHD-FMK; Z-IETD-FMK; FITC; Z-DEVD-FMK; FBS; ROS; HUVEC; PI; GA; GSH; MMP (Δ Ψ m); Apoptosis; Enzyme; Growth; Cysteine endopeptidases; Malignant tumor; Uterine cervix; In vitro; Hela cell line; Female genital diseases; Necrosis; Peptidases; Cell death; Hydrolases; Inhibitor; Uterine cervix diseases; Cervical cancer; Tumor cell; Cancer
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2010.02.034

Gallic acid (GA) is widely distributed in various plants and foods, and its various biological effects have been reported. Here, we evaluated the effects of GA on HeLa cells in relation to cell growth inhibition and death. HeLa cell growth was diminished with an IC
50 of approximately 80
μM GA at 24
h whereas an IC
50 of GA in human umbilical vein endothelial cells (HUVEC) was approximately 400
μM. GA-induced apoptosis and/or necrosis in HeLa cells and HUVEC, which was accompanied by the loss of mitochondrial membrane potential (MMP; Δ
Ψ
m). The percents of MMP (Δ
Ψ
m) loss cells and death cells were lower in HUVEC than HeLa cells. All the tested caspase inhibitors (pan-caspase, caspase-3, -8 or -9 inhibitor) significantly rescued HeLa cells from GA-induced cell death. GA increased reactive oxygen species (ROS) level and GSH (glutathione) depleted cell number in HeLa cells. Caspase inhibitors reduced GSH depleted cell number but not ROS level in GA-treated HeLa cells. In conclusion, GA inhibited the growth of HeLa cells and HUVEC via apoptosis and/or necrosis. The susceptibility of HeLa cells to GA was higher than that of HUVEC. GA-induced HeLa cell death was accompanied by ROS increase and GSH depletion.