β‐Carotene uptake, metabolism, and distribution in BALB/c 3T3 cells

Abstract

Although a growing number of epidemiological studies indicate that dietary beta-carotene has anticarcinogenic activity, the mechanism(s) of beta-carotene protection remains to be definitively established. In this context, in vitro studies of beta-carotene have been, and continue to be, valuable. We examined the following critical features in designing an in vitro system for studying the protection action of beta-carotene: 1) form of beta-carotene used for cellular uptake, 2) cellular metabolism of beta-carotene, and 3) subcellular distribution of beta-carotene. It was determined that beta-carotene added to medium in a water-dispersible formulation is readily taken up by BALB/c 3T3 cells and is located predominantly in cellular membranes. Cellular uptake of beta-carotene added to medium in an organic solvent is greatly reduced. It was also found that intracellular retinol increased significantly after a three-day exposure of BALB/c 3T3 cells to media containing beta-carotene. This result suggests that the ability to metabolize beta-carotene to retinoids is not limited to cells of intestinal origin. The results and methodology described here will be useful in the rational design of in vitro assays for elucidating the mechanism(s) of beta-carotene protective effects at the cellular level.

Carotenoids induce morphological changes in human mammary epithelial cell cultures

“…The antiproliferative and morphological effects of p-carotene exposure in the present study may be attributable to the conversion of this compound to retinoids, which have been shown to induce morphological differentiation in many cell lines (14,27,28). In fact, Warner and co-workers (14) found metabolism of p-carotene to retinol in BALB/c 3T3 cell cultures.…”

“…In fact, Warner and co-workers (14) found metabolism of p-carotene to retinol in BALB/c 3T3 cell cultures. However, the non-provitamin A carotenoid canthaxanthin, which cannot be converted to retinol in the human biologic system, was observed to have an effect similar to that of p-carotene in the present study.…”

“…In a previous study by Rundhaug and colleagues (29), murine fibroblast cells treated with a 10~5 mol/1 p-carotene solution demonstrated cellular concentrations between 1.0 and 2.0 nmol/10 6 cells over a one-week treatment period. Warner and associates (14) achieved a cellular concentration of 0.07 nmol/10 6 cells in BALB/c 3T3 cells after a 36-hour treatment with a water-dispersible P-carotene beadlet formulation. These cellular concentrations of p-carotene are somewhat higher than that obtained in the present study.…”

“…Methods of delivery have included incorporating the carotenoid into beadlets, lipoproteins (such as low-and high-density lipoproteins), and liposomes or dissolving them in solvents such as hexane, chloroform, ethanol, dimethyl sulfoxide, and acetone-dimethyl sulfoxide mixtures (12)(13)(14). However, specific problems are associated with each of these delivery methods, such as cytotoxicity effects, the introduction of other chemical constituents that may act independently of the carotenoid, evaporation of solvent, poor bioavailability of the carotenoid, and limitations in the concentration of carotenoid that can be achieved (13).…”

In vitro effects of ?-carotene for the motility, ATP, and intracellular free Ca2+ concentrations of fowl spermatozoa

“…However, it has been determined that ␤-carotene added to medium was taken up by cultured BALB/c 3T3 cells and was located predominantly in cellular membranes (Wamer et al, 1993). In this study, the motility of demembranated spermatozoa at 25°C, unlike that of intact spermatozoa, was not inhibited by the same concentrations of ␤-carotene with or without Ca 2ϩ or calyculin A.…”