Carotenoids suppress proliferating cell nuclear antigen and cyclin D1 expression in oral carcinogenic models.
The purpose of this study was to investigate the chemopreventive effect of carotenoids on proliferating cell nuclear antigen (PCNA) and cyclin D(1) expression in betel (Areca catechu) quid extract (BQE)-induced hamster oral cancer and human KB cell models, respectively. In the in vivo animal study, 41 hamsters were divided into six groups and treated with 0.3 ml of 0.5% 9,10-dimethyl-1,2-benz[a]-anthracene, BQE, alpha-tocopherol, beta-carotene, lycopene, lutein and mixed carotenoids for 12 weeks. After treatment, the pouches were excised and graded using an immunohistochemical assay of PCNA. In the in vitro cell experiment, KB cells were cultured, and the inhibitory effect of carotenoids (beta-carotene, lycopene and lutein) on cell proliferation was evaluated. Cyclin D(1) and PCNA were evaluated in terms of cell differentiation. In the results, most of the animal lesions showed no overexpression of PCNA. However, in dysplastic lesions, PCNA expressions by the beta-carotene, lutein, lycopene, mixed and vitamin E groups were less than that of the control group. In papilloma lesions, PCNA expressions by the beta-carotene, mixed and vitamin E groups were less severe than that of the control group. PCNA expression by the vitamin E-treated group was less severe than that of the control group. No carcinoma was found in the lycopene or mixed groups. In the cell study, all carotenoids exerted a significant inhibitory effect on KB cell proliferation. Although lycopene suppressed KB cell proliferation at the G(0)/G(1) phase with a significant decrease in PCNA expression, beta-carotene and lutein possessed less of an inhibitory effect and even exhibited elevated cell proliferation at the G(2)/M phase. These results indicate that different carotenoids present various suppressive abilities against PCNA and cyclin D(1) expressions in cell proliferation. In conclusion, carotenoids suppressed the carcinogenesis of induced hamster oral cancer and a cancer cell line by acting as a suppressor which inhibited the expressions of PCNA and cyclin D(1).
Cheng
Hsin-Chung
HC
Orthodontic Department, Taipei Medical University Hospital, Taipei Medical University, Taipei 110, Taiwan.
Chien
Hsin
H
Liao
Chia-Hui
CH
Yang
Yi-Yuan
YY
Huang
Shih-Yi
SY
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002338:Carotenoids / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D006224:Cricetinae; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000187:drug effects; D006801:Humans; D007624:KB Cells; D008297:Male; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis* / Q000187:drug effects
D018809:Proliferating Cell Nuclear Antigen; D019938:Cyclin D1; D002338:Carotenoids; D015127:9,10-Dimethyl-1,2-benzanthracene