Directed lysis of experimental cancer by beta-carotene in liposomes.
The purpose of this study was to extend the knowledge of the antitumor activity of liposomes and to identify, for the first time, the antitumor effect of liposomes with the antioxidant beta-carotene. The administration of the carotenoid encapsulated in in liposomes has the advantages of quantitation, facilitation, and most importantly an increased therapeutic response, resulting in the accentuation of regression of carcinoma in the hamster pouch. Tumors induced after the application of the carcinogen 7,12-dimethylbenz[alpha]anthracene (0.5%) were injected with liposomes composed of phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine in a ratio of 1:1:1 (large unilamellar vesicles). Tumor-bearing animals were divided into four groups, each containing 10 hamsters. The group treated with the liposomes of beta-carotene exhibited a significantly lower tumor burden (approx 5,000-fold difference) than the control tumor group. Electron- and light-micrographic analyses were used to substantiate the gross observations of tumor regression. It was noted that the carcinoma cells endocytozed liposomes in increased numbers compared with normal mucosa treated with liposomes. In addition, non-tumor-bearing hamsters injected with beta-carotene liposomes or liposomes alone did not exhibit any pathological change to the normal mucosa. An inflammatory infiltrate consisting of mononuclear cells, mast cells, and some polymorphonuclear leukocytes was noted, and degranulating polymorphonuclear leukocytes and mast cells and eosinophils predominated in the tumor controls (7,12-dimethylbenz[alpha]anthracene treated only). Notably, not all areas of degenerating dysplasia or early carcinoma exhibited a dense inflammatory response adjacent to the mucosa after the injection of beta-carotene liposomes. The results demonstrate a selective nontoxic therapy to regress experimental oral cancer.
Schwartz
J L
JL
Harvard School of Dental Medicine, Boston, MA 02115.
Flynn
E
E
Trickler
D
D
Shklar
G
G
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000188:drug therapy* / Q000648:ultrastructure; D002338:Carotenoids / Q000008:administration & dosage*; D002610:Cheek; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D004337:Drug Carriers; D008081:Liposomes; D008297:Male; D008647:Mesocricetus; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000648:ultrastructure; D019207:beta Carotene
D004337:Drug Carriers; D008081:Liposomes; D019207:beta Carotene; D002338:Carotenoids