Secalonic acid D induces cell apoptosis in both sensitive and ABCG2-overexpressing multidrug resistant cancer cells through upregulating c-Jun expression

Secalonic acid D (SAD) could inhibit cell growth in not only sensitive cells but also multidrug resistant (MDR) cells. However, the molecular mechanisms need to be elucidated. Here, we identified that SAD possessed potent cytotoxicity in 3 pairs of MDR and their parental sensitive cells including S1-MI-80 and S1, H460/MX20 and H460, MCF-7/ADR and MCF-7 cells. Furthermore, SAD induced cell G2/M phase arrest the downregulation of cyclin B1 and the increase of CDC2 phosphorylation. Importantly, JNK pathway upregulated the expression of c-Jun in protein level and increased c-Jun phosphorylation induced by SAD, which was linked to cell apoptosis c-Jun/Src/STAT3 pathway. To investigate the mechanisms of upregulation of c-Jun protein by SAD, the mRNA expression level and degradation of c-Jun were examined. We found that SAD did not alter the mRNA level of c-Jun but inhibited its proteasome-dependent degradation. Taken together, these results implicate that SAD induces cancer cell death through c-Jun/Src/STAT3 signaling axis by inhibiting the proteasome-dependent degradation of c-Jun in both sensitive cells and ATP-binding cassette transporter sub-family G member 2 (ABCG2)-mediated MDR cells.

Brazilein induced cells apoptosis in human lung cancer A549 cells and its effects on endoplasmic reticulum stress / 重庆医学

Objective To study the apoptotic effect of brazilein on human lung cancer A549 cells and endoplasmic reticulum stress .Methods The cytotoxic activity was tested by MTT assay in A549 cells .The flow cytometry was used to detect apoptosis . Western blotting was performed to detect GRP78 and cyto c protein expression .Results The IC50 values of brazilein against A549 cells was (5 .36 ± 0 .62)μmol/L .After treatment with 0 ,5 ,10 and 20 μmol/L brazilein for 48 h ,the percent of apoptosis was (1 .15 ± 0 .32)% ,(19 .61 ± 4 .52)% ,(30 .18 ± 6 .35)% and (39 .48 ± 7 .44)% respectively .There was significant difference among the different treatment (P< 0 .05) .Compared with control group ,the protein expression of GRP78 and cytosolic cyto c was in‐creased after 5 ,10 and 20 μmol/L brazilein treated for 48 h .Conclusion Brazilein induced apoptosis in human lung cancer A549 cells though endoplasmic reticulum stress pathway .

Progress of study on lapatinib / 中国药理学通报

EGFR/HER-2 is an attractive therapeutic target for solid tumors.Lapatinib is an orally administered dual inhibitor of EGFR/HER-2 tyosine kinases.Preclinical experiments in vitro and in vivo models indicate that lapatinib is active against various solid tumors.Phase Ⅰ trials have shown an acceptable adverse event.Phase Ⅱand Ⅲ trials demonstrate the promising results for the treatment of metastatic,refractory,inflammatory,or brain metastatic breast cancer.With the further developments of biology,the molecular targeted chemotherapy becomes a novel adjuvant therapy for advanced breast cancer patients.

Effectiveness of additive solutions mixed with plasma on the storage of apheresis platelets / 中国输血杂志

6.0,and the expression of CD62P in groupⅠand Ⅱ(32% and 36%)was significantly higher than in control group(28%).However,when the three groups were stored until day 7,all in vitro parameters determined of PCs were better maintained in control group than in the other two.Conclusions The 5-day storage of PCs in additive solution with 50% or 20 % plasma is feasible in terms of the in vitro function in platelet count and pH,however,PCs storaged in additive solutions are more easily activated.