Staphylococcus aureus is susceptible to killing by host-derived fatty acids. Studies were performed to test for a correlation between carotenoid production by S. aureus and protection against oleic acid. Oleic acid killing of cells grown in carotenoid expression medium was determined as the dosage of oleic acid in 2 M NaCl-2 mM EDTA that would kill 20% of the cells in 60 min at 37°C (i.e., the 20% lethal dose). Compared with the wild-type strain (18Z), a carotenoid-deficient mutant strain (18Z-76) and strain 18Z grown in a medium that suppressed carotenoid production both showed increased sensitivity to oleic acid. Spontaneous revertants of strain 18Z-76 that regained the ability to produce carotenoids were as resistant to oleic acid as the wild-type strain. Oleic acid was shown by fluorescence polarization to decrease polarization values. Lower polarization values indicate a more-fluid membrane. To determine whether protection against oleic acid killing might depend on carotenoid stabilization of membranes, fluorescence polarization values were determined for strains showing different levels of carotenoid production. An indirect correlation was found between membrane fluidity and carotenoid production. We were able to conclude that there is a direct correlation between carotenoid production (i.e., cell pigmentation), cell membrane stability, and resistance to oleic acid-induced cell killing.

Vitamin A and some of its metabolites such as beta-all-trans retinoic acid (RA) have been implicated in the regulation of differentiation of normal and malignant epithelial cells in vivo and in vitro. In the present study the effects of RA on the growth and differentiation of 7 cell lines derived from human head and neck squamous-cell carcinomas (HNSCCs) were examined. RA (greater than 0.01 microM) inhibited the proliferation in monolayer culture of 6 of 7 HNSCC cell lines. One cell line (UMSCC-35) was very sensitive, 5 (UMSCC-10A, -19, -30, -22B and HNSCC 1483) were moderately sensitive, and 1 (HNSCC 183) was insensitive. Three of the cell lines (UMSCC-22B, -30, and HNSCC 1483) were capable of forming colonies in semisolid medium--a capability that was suppressed by RA. The HNSCC cell lines expressed various levels of the squamous-cell differentiation markers type I (particulate, epidermal) transglutaminase (TGase) and cholesterol sulfate (CS). RA treatment (I microM, 6 days) decreased TGase activity by more than 50% in 3 (UMSCC-10A, -22B and 1483) of the 7 cell lines, and the effect on UMSCC-22B was dose-dependent. Type II TGase (soluble, tissue type) activity was detected in 3 cell lines, and after RA treatment its activity increased in HNSCC 1483 and 183 cells and decreased in UMSCC-19. Following RA treatment, CS levels decreased by 20, 25, 70, 76, 89 and 91% in cell lines UMSCC-30, -10A, 183, UMSCC-35, -22B, and HNSCC 1483, respectively. The suppression by RA of CS accumulation in the 1483 cells was dose-dependent. Cholesterol sulfotransferase activity, which is responsible for CS synthesis, was suppressed by 40-97% after RA treatment of UMSCC-19, -22B, and HNSCC 1483. Our results demonstrate that RA inhibits the growth and decreases the level of 2 squamous differentiation markers in HNSCC cells.

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