Influence of interleukin-2 on Ca2+ handling in rat ventricular myocytes.

In the present study, we examined the effect of interleukin-2 (IL-2) on cardiomyocyte Ca(2+) handling. The effects of steady-state and transient changes in stimulation frequency on the intracellular Ca(2+) transient were investigated in isolated ventricular myocytes by spectrofluorometry. In the steady state (0.2 Hz) IL-2 (200 U/ml) decreased the amplitude of Ca(2+) transients induced by electrical stimulation and caffeine. At 1.25 mM extracellular Ca(2+) concentration ([Ca(2+)](o)), when the stimulation frequency increased from 0.2 to 1.0 Hz, diastolic Ca(2+) level and peak intracellular Ca(2+) concentration ([Ca(2+)](i)), as well as the amplitude of the transient, increased. The positive frequency relationships of the peak and amplitude of [Ca(2+)](i) transients were blunted in the IL-2-treated myocytes. The effect of IL-2 on the electrically induced [Ca(2+)](i) transient was not normalized by increasing [Ca(2+)](o) to 2.5 mM. IL-2 inhibited the frequency relationship of caffeine-induced Ca(2+) release. Blockade of sarcoplasmic reticulum (SR) Ca(2+)-ATPase with thapsigargin resulted in a significant reduction of the amplitude-frequency relationship of the transient similar to that induced by IL-2. The restitutions were not different between control and IL-2 groups at 1.25 mM [Ca(2+)](o), which was slowed in IL-2-treated myocytes when [Ca(2+)](o) was increased to 2.5 mM. There was no difference in the recirculation fraction (RF) between control and IL-2-treated myocytes at both 1.25 and 2.5 mM [Ca(2+)](o). The effects of IL-2 on frequency relationship, restitution, and RF may be due to depressed SR functions and an increased Na(+)-Ca(2+) exchange activity, but not to any change in L-type Ca(2+) channels.

[Poteintation of vincristine-induced apoptosis by tetrandrine, neferine and dauricine in the human mammary MCF-7 multidrug-resistant cells].

AIM: To investigate the poteintation of vincristine-induecd apoptosis by tetrandrine, neferine and dauricine isolated from Chinese medicinal plants in the human mammary MCF-7 multidrug resistant cells. METHODS: The apoptotic cells were detected by fluorescent staining of a combination of Hoechst 33342 and propidium iodide (PI), flow cytometry and agarose electrophoresis. RESULTS: The apoptotic cells induced by vincristine alone accounted for about 10% of all the cancer cells, while the percentage of apoptotic cells induced by a combination of vincristine with tetrandrine, neferine, or dauricine was found to be significantly higher than that by vincristine alone, and their reversal effects were positively correlated with the drug concentration and the exposure time. In addition, tetrandrine was shown to be the most potent in the reversal efficacy among the three compounds to be tested for apoptosis in vitro. CONCLUSION: Tetrandrine, neferine and dauricine showed obvious potenitiation of vincristine-induced apoptosis in the human mammary MCF-7 multidrug-resistant cells.

Synergistic anticancer effects of tetrandrine combined with doxorubicin or vincristine in vitro.

AIM: To study the interaction between tetrandrine (Tet) and doxorubicin (Dox) or vincristine (Vin) against human breast cancer cell lines MCF-7 and MCF-7/Dox or human nasopharyngeal cancer cell lines KB and KBV200 in vitro. METHODS: Anticancer activities of a drug alone and a drug combination of Tet and Dox or Vin were determined by tetrazolium (MTT) method. The interaction between Tet and Dox or Vin was evaluated by both a value of a sum of fractional inhibitory concentration (SFIC) and an isobologram method. RESULTS: The SFIC values of the three-different-ratio combinations between Tet and Dox ranged from 0.14 to 0.38 for MCF-7, and 0.10 to 0.29 for MCF-7/Dox; those of Tet-Vin combinations ranged from 0.21 to 0.37 for KB, and 0.32 to 0.63 for KBV200. All the SFIC values of the combination between Tet and Dox or Vin were less than 1.0 when the 3 ratios of the 2 drugs in combination were used, and the shapes of isobolic curves obtained from the combination were concave. CONCLUSION: The interaction between Tet and Dox or Vin against the human cancer cells was markedly synergistic.

Effect of artemisinin (qinghaosu) and chloroquine on drug-sensitive and drug-resistant strains of Plasmodium falciparum malaria: use of [2,8-3H]adenosine as an alternative to [G-3H]hypoxanthine in the assessment of in vitro antimalarial activity.

Using [G-3H]hypoxanthine uptake as a radioactive indicator for the growth of malarial parasites, we measured the antimalarial activity of artemisinin (Qinghaosu, QHS) against FCMSU1/Sudan strain (chloroquine-sensitive strain) and FCB K+ strain (chloroquine-resistant strain) of Plasmodium falciparum in continuous culture in vitro. The 50% inhibitory concentrations (IC50) for QHS against FCMSU1/Sudan strain and FCB K+ strain were 2.8 X 10(-8) and 3.0 X 10(-8) M, respectively. On the contrary, the response of the two strains to chloroquine was quite different. The IC50 for chloroquine against FCMSU1/Sudan strain was 5.6 ng/ml, whereas that for the FCB K+ strain was 65.6 ng/ml. Therefore, QHS did not appear to exhibit any cross-resistance with chloroquine. If [2,8-3H]adenosine was used as a radioactive precursor instead of [G-3H]hypoxanthine for the determination of antimalarial activity, virtually identical results were obtained. Therefore, [2,8-3H]adenosine can be used as an alternative to [G-3H]hypoxanthine for the assessment of antimalarial action.