Calcium signaling and T-type calcium channels in cancer cell cycling

Regulation of intracellular calcium is an important signaling mechanism for cell proliferation in both normal and cancerous cells. In normal epithelial cells, free calcium concentration is essential for cells to enter and accomplish the S phase and the M phase of the cell cycle. In contrast, cancerous cells can pass these phases of the cell cycle with much lower cytoplasmic free calcium concentrations, indicating an alternative mechanism has developed for fulfilling the intracellular calcium requirement for an increased rate of DNA synthesis and mitosis of fast replicating cancerous cells. The detailed mechanism underlying the altered calcium loading pathway remains unclear; however, there is a growing body of evidence that suggests the T-type Ca2+ channel is abnormally expressed in cancerous cells and that blockade of these channels may reduce cell proliferation in addition to inducing apoptosis. Recent studies also show that the expression of T-type Ca2+ channels in breast cancer cells is proliferation state dependent, i.e. the channels are expressed at higher levels during the fast-replication period, and once the cells are in a non-proliferation state, expression of this channel isminimal. Therefore, selectively blocking calcium entry into cancerous cells may be a valuable approach for preventing tumor growth. Since T-type Ca2+ channels are not expressed in epithelial cells, selective T-type Ca2+ channel blockers may be useful in the treatment of certain types of cancers.

Potential therapeutic significance of increased expression of aryl hydrocarbon receptor in human gastric cancer

AIM： To determine the functional significance of aryl hydrocarbon receptor （AhR） in gastric carcinogenesis, and to explore the possible role of AhR in gastric cancer （GC） treatment. METHODS： RT-PCR, real-time PCR, and Western blotting were performed to detect AhR expression in 39 GC tissues and five GC cell lines. AhR protein was detected by immunohistochemistry （IHC） in 290 samples： 30 chronic superficial gastritis （CSG）, 30 chronic atrophic gastritis （CAG）, 30 intestinal metapiasia （IN）, 30 atypical hyperplasia （AH）, and 70 GC. The AhR agonist tetrachlorodibenzo-para-dioxin （TCDD） was used to treat AGS cells. MTr assay and flow cytometric analysis were performed to measure the viability, cell cycle and apoptosis of AGS cells.RESULTS： AhR expression was significantly increased in GC tissues and GC cell lines. IHC results indicated that the levels of AhR expression gradually increased, with the lowest levels in CSG, followed by CAG, IM, AH and GC. AhR expression and nuclear translocation were significantly higher in GC than in precancerous tissues. TCDD inhibited proliferation of AGS cells via induction of growth arrest at the G1-S phase. CONCLUSION： AhR plays an important role in gastric carcinogenesis. AhR may be a potential therapeutic target for GC treatment.

Effects of 24 Chinese Medicinal Herbs on Nucleic Acid, Protein and Cell Cycle of Human Lung Adenocarcinoma Cells

Objective: To study the effects of 24 Chinese medicinal herbs on nucleic acid, protein and cellcycle of human lung adenocarcinoma cells. Methods: Using flow cytometry the authors analysed the effects of 24Chinese medicinal herbs (CMH) in compound recipe on proliferation index (PI), DNA index, protein index andratio of various phases in cell cycle of human lung adenocarcinoma cells (SPC-A-1). Results: The PI was morethan 20%, in 4 CMH, while 3 CMH, Gynostemma Pentaphylla, Radix Glehnia, and Radix Ginseng couldstrengthen the body resistance. That suggested using CMH of strengthening body resistance could not only serveas conventional ionic but also as tumor cell inhibitor. Meanwhile the action points of 24 CMH on cell cycle weredifferent from one another. Conclusions: According to these results, Chinese recipes were more effective in clinical practice.

A more robust Boolean model describing inhibitor binding

From the first application of the Boolean model to the cell cycle regulation network of budding yeast,new regulative pathways have been discovered,par-ticularly in the G1/S transition circuit.This discovery called for finer modeling to study the essential biology,and the resulting outcomes are first introduced in the ar-ticle.A traditional Boolean network model set up for the new G1/S transition circuit shows that it cannot correctly simulate real biology unless the model parameters are fine tuned.The deficiency is caused by an overly coarse-grained description of the inhibitor binding process,which shall be overcome by a two-vector model proposed whose robustness is surveyed using random perturba-tions.Simulations show that the proposed two-vector model is much more robust in describing inhibitor binding processes within the Boolean framework.