Gambogic acid (GA) is considered a potent anti-tumor agent for its multiple effects on cancer cells in vitro and in vivo. Low concentrations of GA (0.3-1.2 µmol/L) can suppress invasion of human breast carcinoma cells without affecting cell viability. To get a whole profile of the inhibition on breast cancers, higher concentrations of GA and spontaneous metastatic animal models were employed. Treatment with GA (3 and 6 µmol/L) induced apoptosis in MDA-MB-231 cells and the accumulation of reactive oxygen species (ROS). Furthermore, GA induced PARP cleavage, activation of caspase-3, caspase-8, and caspase-9, as well as an increased ratio of Bax/Bcl-2. Moreover, the translocation of apoptotic inducing factor (AIF) and the release of cytochrome c (Cyt c) from mitochondria were observed, indicating that GA induced apoptosis through accumulation of ROS and mitochondrial apoptotic pathway. GA also inhibited cell survival via blocking Akt/mTOR signaling. In vivo, GA significantly inhibited the xenograft tumor growth and lung metastases in athymic BALB/c nude mice bearing MDA-MB-231 cells. Collectively, these data provide further support for the multiple effects of GA on human breast cancer cells, as well as for its potential application to inhibit tumor growth and prevent metastasis in human cancers.
Concentrations of various trace elements are altered during pregnancy with changes in the mother's physiology and the requirements of growing fetus. The aim of the present longitudinal study was to learn the changes of trace element copper (Cu), zinc (Zn), calcium (Ca), and magnesium (Mg) of normal pregnant woman during different durations of pregnancy and establish the reference values of changes of statistical significance. Blood samples were obtained from 128 normal pregnant women during early (10-14th week), mid (20-24th week), and late (30-34th week) pregnancy and 6-12th week postpartum and 120 healthy unpregnant healthy women. The full blood concentrations of chosen elements were measured by means of an atomic absorption spectrophotometer. Changes on levels of Cu, Ca, and Mg during all the three durations of pregnancy and Zn during mid and late pregnancy and postpartum were of statistical significance and new reference values of them were set in the present study. These new reference values will be helpful in assessing the health status of pregnant women with a socioeconomic and racial background similar to those of our study participants and give treatments to them promptly.
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