Cytotoxicity and arecoline mechanisms in human gingival fibroblasts in vitro

Abstract

Betel nut chewing, like cigarette smoking, is a popular oral habit which impinges on the daily lives of a population of approximately 200 million. People who chew betel nuts have a higher prevalence of periodontal diseases than those who do not. Many of the undesirable effects of betel nuts have been attributed to arecoline, a major component of the particular alkaloid in betel nuts. In this in vitro study, we have focused on the effects of arecoline and the role it could play in periodontal breakdown via its direct effects on human gingival fibroblasts. Human gingival fibroblasts were derived from three healthy individuals undergoing crown-lengthening procedures. We found that arecoline is cytotoxic to human gingival fibroblasts at a concentration higher than 50 micrograms/ml by depleting intracellular thiols and inhibiting mitochondrial activity (P < 0.05). In addition, the cells displayed a marked arrest at G2/M phase in a dose-dependent manner. Repeated and long-term exposure to arecoline could impair the gingival fibroblast functions. As they are cytotoxic, the use of betel nut products in conjunction with periodontal therapy may interfere with optimal healing and/or lead to further periodontal breakdown.

Elevated Snail Expression Mediates Tumor Progression in Areca Quid Chewing-Associated Oral Squamous Cell Carcinoma via Reactive Oxygen Species

“…Arecoline exhibited cytotoxicity at the concentrations higher than 80 µg/ml. Similar studies were reported previously that arecoline had no effects on the cell proliferation in lower doses and inhibited cell growth in higher doses in human gingival fibroblasts [30] and human buccal fibroblasts [31]. Oxidative stress was cited as an important role in promoting cytotoxicity and previous studies have demonstrated that elevated oxidative stress could contribute to carcinogenesis in many type cancer cells [8], [9].…”

Association of Betel Nut with Carcinogenesis: Revisit with a Clinical Perspective

“…Moreover, the expression of p53 regulated p21 (WAF1) and p53 activated DNA repair were repressed by arecoline [87]. Arecoline was cytotoxic to HGF cells due to depletion of intracellular thiols and inhibition of mitochondrial activity and induced cell cycle arrest in HGF cells at G2/M phase in a dose dependent manner [88]. Global gene expression profiling in HGF exposed to arecoline revealed that four genes related to maintenance of genome stability and DNA repair were repressed by arecoline [89].…”

Cell proliferative effect of polyxyloses extracted from the rhizomes of wild turmeric,Curcuma aromatica

“…At a concentration of 10 and 100 μg/mL the P21 fraction slightly (but not statistically) and markedly (and statistically p < 0.05) inhibited the cell growth (92.2% ± 3.5% relative to the control (Figure 4). Thus, P21 can decrease or obstruct mitochondrial function leading to insufficient energy levels in the human gingival fibroblast cells for their repair and regeneration (Chang et al, 2001;Issa et al, 2008). Certainly the polysaccharide arecoline is reported to be cytotoxic to human gingival fibroblast cells by inhibiting the mitochondrial function (Chang et al, 2001), where 50-200 μg/mL arecoline can inhibits 16-56% of mitochondrial activity.…”

“…Thus, P21 can decrease or obstruct mitochondrial function leading to insufficient energy levels in the human gingival fibroblast cells for their repair and regeneration (Chang et al, 2001;Issa et al, 2008). Certainly the polysaccharide arecoline is reported to be cytotoxic to human gingival fibroblast cells by inhibiting the mitochondrial function (Chang et al, 2001), where 50-200 μg/mL arecoline can inhibits 16-56% of mitochondrial activity. Given that here P21 at 100 μg/mL appeared to inhibit around 90% of mitochondrial activity (Figure 4), then P21 would appear to be a significantly more efficient inhibitor than arecoline.…”