Studies on promoting activity of Taiwan betel quid ingredients in hamster buccal pouch carcinogenesis

doi:10.1016/0964-1955(96)00018-8

European Journal of Cancer Part B: Oral Oncology

Volume 32, Issue 5, September 1996, Pages 343-346

European Journal of ...

https://doi.org/10.1016/0964-1955(96)00018-8 Get rights and content

Abstract

Previous studies indicated that Taiwan betel quid is a promoter rather than an initiator during the carcinogenesis of hamster buccal pouch carcinoma. The maximum promoting activity can be demonstrated 24 weeks after betel quid implantation, following an initial application of 0.5% DMBA (7,12-dimethyl benzanthracene) three times per week for 4 weeks. In the present study, components of Taiwan betel quid and its additives (dry betel nut fibre, piper betel, slaked lime, cold aqueous extract, and hot aqueous extract) were applied respectively or in various combinations to investigate their promoting activity. One hundred and thirty Syrian hamsters were divided into 13 groups based on different combinations of the betel quid ingredients applied. The incidence of tumours in the hamster buccal pouch was significantly higher in groups exposed to dry betel nut fibre (P < 0.01) and cold aqueous extract (P < 0.05). The results indicate that betel nut fibre and cold aqueous extract are the major components of betel quid that may promote carcinogenesis in the hamster buccal pouch.

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Cited by (35)

Arecoline N-oxide initiates oral carcinogenesis and arecoline N-oxide mercapturic acid attenuates the cancer risk
2021, Life Sciences
Citation Excerpt :
Approximately 80% of oral cancer patients are associated with BQ chewing in Taiwan [8]. Several findings revealed that the areca nut might be performed as a promoter, not an initiator for oral carcinogenesis [9–11]. Then, our team has reported that the arecoline N-oxide (ANO) revealed higher toxicity in oral potentially malignant disorders (OPMD) inductive activity in the C57BL/6 mice model [12].
Arecoline N-oxide (ANO), an oxidative metabolite of the areca nut, is a predictable initiator in carcinogenesis. The mechanisms of arecoline metabolites in human cancer specimens is still limited. This present study aims to estimate the oral squamous cell carcinoma (OSCC) inductive activity between arecoline metabolites in human cancer specimens/OSCC cells. We have collected 22 pairs (tumor and non-tumor part) of patient's specimens and checked for clinical characteristics. The identification of arecoline and its metabolites levels by using LC-MS/MS. The NOD/SCID mice model was used to check the OSCC inductive activity. The tumor part of OSCC samples exhibited higher levels of arecoline and ANO. Besides, ANO treated mice accelerates the NOTCH1, IL-17a and IL-1β expressions compared to the control mice. ANO exhibited higher cytotoxicity, intracellular ROS levels and decline in antioxidant enzyme levels in OC-3 cells. The protein expression of NOTCH1 and proliferation marker levels are significantly lower in NOM treated cells. Overall, ANO induced initial stage carcinogenesis in the oral cavity via inflammation, ROS and depletion of antioxidant enzymes. Arecoline N-oxide mercapturic acid (NOM) attenuates the initiation of oral carcinogenesis.
Biotechnological intervention in betelvine (Piper betle L.): A review on recent advances and future prospects
2016, Asian Pacific Journal of Tropical Medicine
Citation Excerpt :
Despite of its medicinal uses, since long time betelvine has been a crucial point of argument that the consumption of betel leads to oral cancer. In many experiments, several scientists have proved that chewing of betel leaves along with areca nut, catechu, slaked lime and often tobacco induces cancer [19–25]. In contrary scientific studies have shown that betel leaf is itself devoid of mutagenic and carcinogenic effects.
Betelvine (Piper betle L.) is cultivated for its deep green heart shaped leaf for (15–20) million Indian and 2 billion foreign consumers annually. The crop provides Rs (6 000–7 000) million of national income per year and at the same time leaves worth Rs (30–40) million is exported to other countries. The leaves are not only used directly for chewing purposes but also possesses antioxidant, anti-inflammatory, anti-apoptotic, anti-cancer and anti-microbial properties. Besides, the leaves also contain eugenol rich essential oil (1%–3%) which is the source for medicine, stimulant, antiseptic, tonic and other ayurvedic formulations. The essential oil also contains chavibetol, caryophyllene and methyl eugenol which are the potent source for preparation in ayurvedic medicine and herbal products. Cost of betelvine essential oil is 10$ per 5 mL. In spite of its great economical and medicinal importance betelvine is still neglected by the researchers for proper characterization and authentication for selection of elite landraces. Lack of awareness among people, use of same planting material for many generations, existing of many synonyms for a single landraces, no proper characterization of available landraces are some of the significant constraints for its commercialization. Our review endeavours a complete advance in the research on betelvine, existing lacunae for its proper characterization and commercial cultivation. It also attempts to provide a comprehensive account on biotechnological interventions made in betelvine aimed at complementing conventional programmes for improvement of this nutraceutically important cash crop.
Cytotoxicity and transformation of C3H10T1/2 cells induced by areca nut components
2016, Journal of the Formosan Medical Association
Citation Excerpt :
This result suggests that ANE is not a strong complete carcinogen, not simulating the well-known complete carcinogen MCA that may induce transformed foci alone. BQ components have been suggested to be tumor promoters by using both in vitro and in vivo models.26–29 Previous studies have found that BQ extract may promote the transformation of JB6 cells and can be a tumor promoter.27
Betel quid (BQ) chewing is popular in Taiwan and many other countries. There are about 200–600 million BQ chewers in the world. BQ chewing is one major risk factor of oral cancer and oral submucous fibrosis (OSF). While areca nut (AN), a main component of BQ, exhibits genotoxicity, its transformation capacity and its role in the initiation and promotion stages of carcinogenesis are not fully clear.
Mouse C3H10T1/2 cells were exposed to AN extract (ANE) for 24 hours. Cytotoxicity was evaluated by colony forming efficiency. For the transformation assay, C3H10T1/2 cells were exposed to ANE for 24 hours and then incubated in medium with/without 12-O-tetradecanolylphorbol-13-acetate (TPA; a tumor promoter) for 42 days. Cells were stained with Giemsa and type II and type III transformed foci were counted for analysis of the transformation capacity of ANE.
ANE exhibited cytotoxicity to C3H10T/12 cells at concentrations higher than 320 μg/mL as shown by a decrease in colony numbers. ANE (80–640 μg/mL) alone mildly stimulated the transformed foci formation (p > 0.05). In the presence of TPA, ANE (80–640 μg/mL) markedly stimulated the transformed foci formation. The percentage of dishes with foci increased from 0% in controls to 20% in ANE (80 μg/mL and 320 μg/mL)-treated groups and further increased to 65–94% in ANE plus TPA groups.
These results indicate that ANE is a weak complete carcinogen. ANE is an effective tumor initiator and can induce malignant transformation of C3H10T1/2 cells in the presence of a tumor promoter. ANE may be involved in multistep chemical carcinogenesis by its malignant transformation capacity.
Up-regulation of matrix metalloproteinase-8 by betel quid extract and arecoline and its role in 2D motility
2007, Oral Oncology
Citation Excerpt :
There are about 200–600 million BQ chewers in the world, including Taiwan. More than 2400 new cases of oral cancer are diagnosed each year in Taiwan due to the prevalent use of BQ.20,21 There are several distinct compositions of BQ, among which areca nut is the essential component, whose extract induces growth arrest and senescence-associated phenotypes in human oral keratinocyte.22
Betel quid (BQ) and matrix metalloproteinase-8 (MMP-8) play roles in oral diseases. Here, we analyzed the regulation of MMP-8 by BQ and its effect on cell migration. We found that BQ extract (BQE) increased the secretion of an 85 kDa caseinolytic proteinase, specifically precipitated by an anti-MMP-8 antibody, in the culture medium of OECM-1, an oral squamous cell carcinoma (OSCC) cell line. BQE also stimulated MMP-8 secretion in an esophageal carcinoma cell line, CE81T/VGH, in a dose-dependent manner, and MMP-8 protein was maximally expressed at 24 h after BQE treatment in OECM-1. The BQE-induced MMP-8 expression was dose-dependently inhibited by PD98059. Arecoline, the major alkaloid of areca nut, was tested to dose-dependently up-regulate MMP-8 protein level. Moreover, both arecoline- (4.7-fold) and BQE-selected (5.5-fold) CE81T/VGH cells expressed higher MMP-8 protein level and exhibited enhanced two-dimensional (2D) motility (p = 0.009 in both cells) than parental cells. The enhanced motility of arecoline- (p = 0.006) and BQE-selected (p = 0.002) cells was both specifically blocked by an anti-MMP-8 antibody. We conclude that BQ may accelerate tumor migration by stimulating MMP-8 expression through MEK pathway in at least some carcinomas of the upper aerodigestive tract. Furthermore, arecoline may be one of the positive MMP-8 regulators among BQ ingredients.
Hamsters chewing betel quid or areca nut directly show a decrease in body weight and survival rates with concomitant epithelial hyperplasia of cheek pouch
2004, Oral Oncology
Betel quid (BQ) chewing is strongly associated with the occurrence of oral leukoplakia, oral submucous fibrosis, and oral cancer. There are about 200–600 million BQ chewers in the world. Previous animal studies support the potential carcinogenicity of BQ in different test systems. However, little animal experiment has let hamsters or rats to chew BQ directly, similar to that in humans. In the present study, we established a hamster model of chewing BQ or areca nut (AN). A total of 81 2-week-old hamsters were randomly divided into three groups: 25 for control group, 28 for BQ-chewing group, and 28 for AN-chewing group. These animals were fed with powdered diet with/without BQ or AN for 18 months. Although the consumption of BQ or AN showed some variations, hamsters fed with powdered diet could chew and grind AN or BQ into small pieces of coarse fibers during the entire experimental period. The survival rate of AN-chewing hamsters decreased significantly after 6 months of exposure. The mean survival time was 15.6 ± 0.9 months for control animals, 13.6 ± 0.98 months for AN-chewing animals, and 15.7 ± 0.55 months for BQ-chewing animals. The body weight of BQ- or AN-chewing animals also decreased after 4–13 months. Hamsters fed with AN for 18 months showed hyperkeratosis in 80% and acanthosis in 50% of cheek pouches. Animals fed with BQ for 18 months also showed hyperkeratosis in 93% and acanthosis in 14% of cheek pouches. These results indicate that AN and BQ components may induce alterations in proliferation and differentiation of oral epithelial cells. Animal model of chewing BQ or AN can be useful for future tumor initiation, promotion and chemoprevention experiments simulating the condition of BQ chewing in humans.
The mRNA profile of genes in betel quid chewing oral cancer patients
2004, Oral Oncology
Oral cancer is one of the most common types of human cancer in the world. Although the risk factors for oral cancer are well-recognized in different countries, the molecular mechanism responsible for this malignancy remains elusive particularly in the countries where betel quid chewing is prevalent. The cDNA microarray analysis was used to analyse the mRNA expression patterns of 1177 genes in ten oral cancer patients with betel quid chewing history. Eighty-four genes involving cell adhesion, cell shape, growth, apoptosis, angiogenesis, metastasis, and metabolism were deregulated. Although the expression profile of these genes was shared by certain clinical patients, there was no significant association of the expression profile with clinical staging. Functional implication of four validated genes including caspase-1, STAT-1, COX-2 and pleiotrophin was discussed. This study provides pilot data for understanding the pathogenesis of oral cancer in countries like Taiwan where betel quid chewing is prevalent.

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PaperStudies on promoting activity of Taiwan betel quid ingredients in hamster buccal pouch carcinogenesis

Abstract

Oral Surg

Oral Surg Oral Med Oral Pathol

Cancer Lett

Lancet

An epidemiological study of oral and pharyngeal cancer in central and south-east Asia

Bull WHO

A statistical study of oral carcinomas in Taiwan with emphasis on the relationship with betel nut chewing: a preliminary report

J Formosan Med Assoc

Carcinogenic effect of a dimethylsulphoxide extract of betel nut on the mucosa of the hamster buccal pouch

Nature

Betel quid chewing and oral cancer: experimental studies on hamsters

Int J Cancer

A statistical study on 234 cases of oral carcinoma

J Otolaryngol Soc ROC

A study of betel quid carcinogenesis—VIII. Carcinogenicity of 3-(methylnitrosamino) propionaldehyde in F344 rats

Carcinogenesis

Studies on Taiwan betel quid Carcinogenicity in hamster cheek pouch

Chinese Dent J

Experimental carcinogenesis in the cheek pouch of the Syrian hamster

J Dent Res

The effect of a carcinogen (DMBA) applied to the hamster's buccal pouch in combination with croton oil

Oral Surg

Paper
Studies on promoting activity of Taiwan betel quid ingredients in hamster buccal pouch carcinogenesis