Nobuhito Onogi

Antiproliferative effect of carotenoids on human colon cancer cells without conversion to retinoic acid

The present study employed two human colon cancer cell lines, DLD-1 and Colo 320DM, to investigate whether the provitamin A activity of carotenoids is necessary for their antitumor effect on colon cancer. Carotenoids, including alpha- and beta-carotene and canthaxanthin, significantly suppressed cell viability [measured by tetrazolium (MTT) assay], DNA synthesis (measured by [3H]thymidine uptake), and cell proliferation (measured by cell counting) and thus showed growth-inhibitory effects on both cancer cell lines. Because canthaxanthin does not have provitamin A activity, these results suggest that the carotenoid directly inhibited the cell growth. Moreover, the effective dose of retinoic acid, an active metabolite of vitamin A, was much higher than that of alpha- or beta-carotene. A retinoic acid-inducible gene, retinoic acid receptor-beta, was not enhanced in either type of cancer cell by treatment with alpha- or beta-carotene. Therefore, like canthaxanthin, alpha- and beta-carotene might also exert their tumor-suppressing effects without being converted to retinoids. These results suggest that a certain antitumor activity of carotenoids may not necessarily require their provitamin A activity.

Suppression of mouse skin papilloma by canthaxanthin and β-carotene in vivo : Possibility of the regression of tumorigenesis by carotenoids without conversion to retinoic acid

Using mouse skin papilloma as a model system, we examined whether the antitumorigenic activity of carotenoids was related to their provitamin A activity. Oral administration of canthaxanthin (CX) or beta-carotene at 200 mg/kg/day for 14 days significantly reduced the cumulative size of papillomas induced on the skin by 9,10-dimethyl-1,2-benzanthracene (p < 0.05), after the accumulation of these carotenoids in the tumors. The levels of a protooncogene, c-myc, were simultaneously suppressed in papillomas in carotenoid-treated mice. Because CX cannot be converted metabolically to retinoids, these results suggested that CX directly inhibited the growth of papillomas. Neither the accumulation of retinoids nor the expression of a retinoic acid-inducible gene, retinoic acid receptor-beta, was found in papillomas of CX- and beta-carotene-treated mice, suggesting that, like CX, beta-carotene might exert the tumor-suppressing effect without being converted to retinoids. Thus a certain antitumorigenic activity of carotenoids appears not necessarily to require their provitamin A activity.

3507 IS AN ESOPHAGEAL DYSFUNCTION IN PSS A MOST IMPORTANT CONTRIBUTIVE FACTOR IN SEVERE REFLUX ESOPHAGITIS

Background: Esophageal dysfunction is commonly observed in patients with progressive systemic sclerosis (PSS). We already reported that the lower esophageal primary pressures were significantly decreased according to the severity of PSS. On the other hand, reflux esophagitis (RE) is revealed in many PSS patients by endoscopic examination. The aim of this study was to investigate the correlations between the severity of RE and manometric study of PSS. Patients and Methods: Gastrointestinal endoscopic examination was performed on 30 patients with PSS (3 males, 27 females). The severity of the endoscopic findings of RE were diagnosed under the LA classification. There were no findings (Grade O) in 10 cases, Grade A in 13 cases, Grade B in 4 cases, and Grade C in 3 cases. At the same time we conducted an examination regarding esophageal hiatal hernia and the area of the fundic gland mucosa which is considered the source of gastric acid secretion. Using esophageal manometry, we measured upper esophageal sphincter pressure (UESP), lower esophageal sphincter pressure (LESP), and primary peristaltic pressure (PP) at 20, 25, 30, and 35 cm from the incisor. The severity of PSS was determined according to the PSS Research Group supported by the Ministry of Health and Welfare of Japan. The six domains of this score are as follows: sclerodactylia, pitting scars, pulmonary fibrosis, skin pigmentation, shortened frenulum, and flexion contracture. The severities were determined according to the number of positive clinical features. Statistical analysis was performed using Spearmans rank correlation in regard to age, sex, LA classification, esophageal hiatal hernia, PPs at every point and LESP. Results: There was a significant correlation between only the severity of RE and esophageal hiatal hernia (P