Bisabololoxide A, one of the constituents in German chamomile extract, attenuates cell death induced by calcium overload.

Bisabololoxide A (BSBO), main constituents in German chamomile extract, is responsible for antipruritic effect. In previous study, the incubation with 30-100 µM BSBO for 24 h exerted cytotoxic and proapoptotic effects on rat thymocytes. To further characterize BSBO cytotoxicity, the effect on the cells suffering from calcium overload by calcium ionophore A23187 was examined. A23187 induced Ca(2+) -dependent cell death. Contrary to our expectation, 1-10 µM BSBO inhibited A23187-induced increase in cell lethality of rat thymocytes. BSBO attenuated A23187-induced increases in populations of shrunken living cells, phosphatidylserine-exposed living cells, and dead cells, without affecting the increase in intracellular Ca(2+) concentration and the Ca(2+) -dependent hyperpolarization. The effect of BSBO on A23187-treated cells may be unique because the activation of Ca(2+) -dependent K(+) channels is required for cell shrinkage, externalization of phosphatidylserine, and cell death in some cells. The cell death induced by A23187 was not inhibited by Z-VAD-FMK, a pan-inhibitor of caspases. Thus, the cell death may be a necrosis with some features observed during an early stage of apoptosis. These results suggest that BSBO at low micromolar concentrations is cytoprotective against calcium overload.

A comparison of the cellular actions of polaprezinc (zinc-L-carnosine) and ZnCl2.

AIMS: Zinc supplementation has been proven to be beneficial for the prevention of some health problems. Many zinc supplements are used for medical and nutritional purposes. However, it is difficult to distinguish between them in terms of their cellular actions. We compared the cellular actions of polaprezinc (zinc-l-carnosine) with those of ZnCl(2) in order to determine whether polaprezinc has greater zinc-related actions than ZnCl(2). MAIN METHODS: Cellular actions of polaprezinc and ZnCl(2) were estimated by flow-cytometric techniques with appropriate fluorescent probes in rat thymocytes. KEY FINDINGS: Both agents had almost equal stimulatory effects on the intracellular Zn(2+) level and cellular level of nonprotein thiol in a similar concentration-dependent manner. However, the increase in cell lethality caused by ZnCl(2) under severe oxidative stress was significantly greater than that caused by polaprezinc. SIGNIFICANCE: There are various zinc supplements, for example, zinc gluconate, zinc picolinate, and zinc methionine. However, the differences in their cellular actions have not been elucidated to date. Such studies could distinguish between zinc supplements.

Cytotoxic action of bisabololoxide A of German chamomile on human leukemia K562 cells in combination with 5-fluorouracil.

German chamomile (Matricaria recutita L.) is a popular ingredient in herbal teas. In previous study, micromolar bisabololoxide A, one of main constituents in German chamomile, exerted cytotoxic action on rat thymocyte, a normal non-proliferative cell. This result prompted us to study the effect of bisabololoxide A on proliferative cancer cells and to seek the possibility of its use with 5-fluorouracil, an anticancer agent. In this study, the effect of micromolar bisabololoxide A on human leukemia K562 cells was cytometrically examined. Although the incubation of K562 cells with 10 µM bisabololoxide A for 72h did not significantly increase the percentage populations of dead cells and shrunken cells, the inhibitory action on the growth was obviously observed. It was not the case for the concentrations of less than 5 µM. The threshold concentration of bisabololoxide A to exert the cytotoxic action on K562 cells was ascertained to be 5-10 µM. Bisabololoxide A at 5-10 µM did not exert cytotoxic action on normal non-proliferative cells (rat thymocytes) in our previous study. Since the antiproliferative action of micromolar bisabololoxide A on cancerous cells was expected to be beneficial to cancer treatment, the modification of antiproliferative action of 5-fluorouracil (3-30 µM) by bisabololoxide A was studied. The combination of 5-fluorouracil and bisabololoxide further inhibited the growth of K562 cells although the additive inhibition of growth by bisabololoxide A became smaller as the concentration of 5-fluorouracil increased. Therefore, it is suggested that the simultaneous application of German chamomile containing bisabololoxide A may reduce the dose of 5-fluorouracil.