This effect on cell cycle was caused by inhibition of microtubule polymerization. Treatment of hNPCs with PDA 66 also led to an attenuated proliferation and an increased rate of apoptosis. An antiproliferative effect was also demonstrated in human cell lines of lung cancer and glio blastoma. Similar results were obtained in our study. The analyzed ALL cells showed http://www.selleckchem.com/products/MG132.html a significant increase of apoptosis 48 h after treatment with PDA 66. Conclusion We demonstrated for the first time a significant and pronounced antiproliferative influence of PDA 66 on ALL cells. In addition, we showed an induction of apop tosis via cleavage of caspases as well as suppression of metabolic activity. While there was an effect on cell cycle progression, no influence on the Wnt B catenin signaling pathway was observed.
The investigation of en zyme activity of GSK3B showed a minor inhibitory effect compared to the analogue substance SB 216763. Never theless, the herein observed anti tumoral potential in ALL and the previous seen effects in neoplastic tissues classify PDA 66 as a promising novel therapeutic agent candidate. Consequently, the detailed analyses of PDA 66 mediated effects should be further elucidated and val idated in vivo as a base for a perspective therapeutic consideration. Background Prostate cancer is the second most frequently diagnosed cancer in men and the second leading cause of cancer related death in American men. There is an estimated 238,590 new cases of prostate cancer predicted in the US this year and an estimated 29,720 deaths due to prostate cancer.
Despite advances in radiation and chemother apy, prostate cancer is a leading cause of cancer death. Radiation and chemotherapy treatment remain central to prostate cancer treatment. These treatments can, however, produce a number of side effects such as neutropenia, urinary and bowel symptoms, hair loss, and fatigue. There is, therefore, a critical need to develop tumor specific therapies for prostate cancer. Selective activation of anti cancer drugs within cancer cells is a promising strategy to minimize the toxic effects of anticancer drugs on normal tissues. As indi cated in Figure 1, the esterase prodrug strategy utilizes pharmacological compounds that are blocked by esterifi cation but are activated when cancer cell esterases cleave the ester bond and release the active drug.
A degree of specificity can be achieved if the cancer cell esterase is overexpressed compared to normal tissue. In order to optimize potential chemotherapeutic prodrug esters it is important to characterize and identify any differentially expressed esterases. Yamazaki et al. examined the esterase activity profiles of various human and animal cancer tumors using Crenolanib buy n PAGE and esterase activity staining. These researchers found that lysates from cancer tumors often had a different level of activity and a different stereoselectivity towards sev eral chiral esters than the corresponding normal tissues.