Retinoid and carotenoid angiogenesis: A possible explanation for enhanced oral carcinogenesis

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The carotenoids β-carotene and canthaxanthin and the retinoid 13-cis- retinoic acid (13-RA) have inhibited oral carcinogenesis in the hamster cheek pouch (16 wks, 3 times/wk at 1.4 mg/kg) induced by an 0.5% solution of 7,12- dimethylbenz[a]anthracene (DMBA). However, 13-RA at a higher dose (>2.0 mg/kg per treatment) increased squamous cell carcinoma growth (Eur J Cancer Clin Oncol 24, 839850, 1988). 13-RA, β-carotene, and canthaxanthin administered to 60 hamsters (16 wks, 3 times/wk, 10 mg/kg) altered neovascularization characterized by immunohistochemistry for transforming growth factor-α (TGF- α) and factor VIII. 13-RA + DMBA resulted in more smaller-sized tumors, with a reduced volume and tumor burden (tumor controls, 185.9; 13-RA + DMBA, 151.0). The carotenoids reduced the number and the sizes of the carcinomas formed (β-carotene, 60 tumors, 142.3 x 103 mm3; canthaxanthin, 30 tumors, 116.1 x 103 mm3). Factor VIII and TGF-α were expressed in high intensity at cancer sites of the 13-RA + DMBA and DMBA groups with >50 and >10 cells, respectively, per x400 field. In contrast, β-carotene- and canthaxanthin + DMBA treated pouches showed >20 and 5 cells, respectively, per x400 field for factor VIII and TGF-α. These results suggest that 13-RA treatment may increase vascular growth, but the carotenoids also produced enhanced levels of endothelial cell growth and TGF-α compared with the untreated mucosa. The carotenoids may enhance tumor growth under the appropriate carcinogenic environment.

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