Reversal of doxorubicin resistance by guggulsterone of Commiphora mukul in vivo.

Our previous study has shown co-administration of guggulsterone resulted in significant increase in chemosensitivity of multidrug-resistant human breast cancer MCF-7/DOX cells to doxorubicin (DOX) in vitro. The present study was designed to investigate whether guggulsterone had the similar modulatory activities in vivo. MCF-7/DOX and MCF-7 xenograft mice models were established. At the end of the experiment (day 28), doxorubicin treatment alone did not significantly inhibit tumor growth in MCF-7/DOX xenograft, indicating that it retained doxorubicin resistance. Whereas, doxorubicin treatment alone significantly inhibited tumor growth in MCF-7 xenograft, suggesting that it maintained doxorubicin sensitivity. When doxorubicin and guggulsterone were co-administrated, their antitumor activities were augmented in MCF-7/DOX xenograft. However, combination therapy did not enhance the antitumor effects of doxorubicin in MCF-7 xenograft. The expression of proliferative cell nuclear antigens PCNA and Ki67 after doxorubicin treatment alone was not significantly different from that of vehicle group in MCF-7/DOX xenograft. On the contrary, doxorubicin treatment alone significantly reduced PCNA and Ki67 expression in MCF-7 xenograft. Combination therapy also significantly reduced PCNA and Ki67 expression in MCF-7/DOX xenograft, compared to doxorubicin treatment alone. However, combination therapy did not enhance the inhibitory effects of doxorubicin on PCNA and Ki67 expression in MCF-7 xenograft. Examining the apoptotic index by TUNEL assay showed similar results. Further studies demonstrated the inhibitory effects of guggulsterone on Bcl-2 and P-glycoprotein expression were the possible reason to increase chemosensitivity of MCF-7/DOX cells to doxorubicin in vivo. Examining body weight, hematological parameters, hepatic, cardiac and gastrointestinal tracts histopathology revealed that no significant signs of toxicity were related to guggulsterone. Guggulsterone might reverse doxorubicin resistance in vivo, with no severe side effects.

Groundwater geochemistry and its implications for arsenic mobilization in shallow aquifers of the Hetao Basin, Inner Mongolia.

Arsenic concentrations in shallow groundwaters from the Hetao Basin of Inner Mongolia range between 0.6 and 572 microg/L. High As groundwaters generally occur in the shallow alluvial-lacustrine aquifers, which are mainly composed of black (or dark grey) fine sands in a reducing environment. They are characterized by high concentrations of dissolved Fe, Mn, HCO(3)(-), P and S(2-), and low concentrations of NO(3)(-) and SO(4)(2-). Low SO(4)(2-) coupled with high S(2-) suggests that SO(4)(2-) reduction has been an active process. In the reducing groundwaters, inorganic As(III) accounts for around 75% of total dissolved As. Total As contents in the sediments from three representative boreholes are observed to be 7.3-73.3 mg/kg (average of 18.9 mg/kg). The total As is mildly-strongly correlated with total Fe and total Mn, while a quite weak correlation exists between total As and total S, suggesting that the As is associated with Fe-Mn oxides, rather than sulfides in the sediments. It is found in the sequential extraction that chemically active As is mainly bound to Fe-Mn oxides, up to 3500 microg/kg. The mobilization of As under reducing conditions is believed to include reductive dissolution of Fe-Mn oxides and reduction of adsorbed As. Although exchangeable As is labile and very vulnerable to hydrogeochemical condition, the contribution is relatively limited due to the low concentrations. The competition between As and other anions (such as HPO(4)(2-)) for binding sites on Fe-Mn oxides may also give rise to the release of As into groundwater. Slow groundwater movement helps accumulation of the released As in the groundwaters.