Anti-proliferative effect of methanolic extract of Gracilaria tenuistipitata on oral cancer cells involves apoptosis, DNA damage, and oxidative stress

Chi-Chen Yeh,Ya-Ching Chan,Hsueh-Wei Chang,Li-Yeh Chuang,Jen-Yang Tang,Fang-Rong Chang,Jin-Ching Lee,Chao-Neng Tseng,Hurng-Wern Huang,Jing-Iong Yang,You-Cheng Hseu

doi:10.1186/1472-6882-12-142

Abstract

BackgroundMethanolic extracts of Gracilaria tenuistipitata (MEGT) were obtained from the edible red algae. Previously, we found that water extract of G. tenuistipitata was able to modulate oxidative stress-induced DNA damage and its related cellular responses.MethodsIn this study, the methanol extraction product MEGT was used to evaluate the cell growth inhibition in oral cancer cells and its possible mechanism was investigated.ResultsThe cell viability of MEGT treated Ca9-22 oral cancer cell line was significantly decreased in a dose–response manner (p < 0.05). The sub-G1 population and annexin V intensity of MEGT-treated Ca9-22 cancer cells were significantly increased in a dose–response manner (p < 0.0005 and p < 0.001, respectively). The γH2AX intensities of MEGT-treated Ca9-22 cancer cells were significantly increased in a dose–response manner (p < 0.05). The reactive oxygen species (ROS) and glutathione (GSH)-positive intensities of MEGT-treated Ca9-22 oral cancer cells were significantly increased and decreased, respectively, in a dose–response manner (p < 0.05). The DiOC2(3) intensity for mitochondrial membrane potential (MMP) of MEGT-treated Ca9-22 cancer cells was significantly decreased in a dose–response manner (p < 0.05).ConclusionsThese results indicated that MEGT had apoptosis-based cytotoxicity against oral cancer cells through the DNA damage, ROS induction, and mitochondrial depolarization. Therefore, MEGT derived from the edible algae may have potential therapeutic effects against oral squamous cell carcinoma (OSCC).

Highlights

Methanolic extracts of Gracilaria tenuistipitata (MEGT) were obtained from the edible red algae
Changes of cell cycle distribution in MEGT-treated Ca9-22 oral cancer cells The G1 percentages were significantly increased at the concentrations from 0 to 0.25 mg/ml MEGT leading to G1 arrest (Figure 2)
This MEGT-induced sub-G1 accumulation of Ca9-22 oral cancer cells was significantly increased in a dose–response manner (p < 0.0005)

Summary

Introduction

Methanolic extracts of Gracilaria tenuistipitata (MEGT) were obtained from the edible red algae. The bioactive compounds of the genus Gracilaria had been summarized [16,17] and mainly classified by water [18,19,20] and ethanol/methanol [21,22,23] extractions. Most of these studies focus on health promoting effects, such as anti-inflammatory, anti-hypercholesterolemic, antioxidative, and antimicrobial properties rather than on cancer therapy

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Conclusion