Activation of the mitochondria-driven pathway of apoptosis in human PC-3 prostate cancer cells by a novel hydrophilic paclitaxel derivative, 7-xylosyl-10-deacetylpaclitaxel

Abstract

Paclitaxel, a natural product originally isolated from Taxus brevifolia, belongs to the most successful anticancer drugs. Nevertheless, its poor water solubility represents a considerable disadvantage in clinical use, and novel derivatives with improved pharmacological features are required. We isolated 7-xylosyl-10-deacetylpaclitaxel from Taxus chinensis, which reveals higher water solubility than paclitaxel. This compound induced mitotic cell cycle arrest and apoptosis as measured by flow cytometry, DNA laddering, and transmission electron microscopy. Pro-apoptotic Bax and Bad protein expression was up-regulated and antiapoptotic Bcl-2 and Bcl-X L expression down-regulated, which lead to a disturbance of the mitochondrial membrane permeability and to the activation of caspase-9. In turn, caspase-9 activated downstream caspases-3 and-6, but not caspase-8. Bid was also activated by caspase-3. Reversely, treatment with a caspase-10-specific inhibitor could not protect PC-3 cells from 7-xylosyl-10-deacetyl-paclitaxeltriggered apoptosis. Moreover, 7-xylosyl-10-deacetylpaclitaxel had no effect on the expression of CD95 and NF-κB proteins, indicating that apoptosis was induced through the mitochondrial-dependent pathway in PC-3 cells.

Combination of 2-methoxyestradiol (2-ME2) and eugenol for apoptosis induction synergistically in androgen independent prostate cancer cells

“…However when the two agents are combined, the loss of MMP is increased to 90% indicating that the combination is more effective in disrupting MMP. It has been demonstrated that activation of mitochondria driven pathway is a potential mechanism for induction of apoptosis by several compounds including dichloroacetate, sodium selenite and paclitaxel derivative in prostate cancer cells [35][36][37]. Our results showing induction of apoptosis through modulation of MMP is consistent with these observations.…”

Preparation, characterization, and antitumor activities of folate-decorated docetaxel-loaded human serum albumin nanoparticles

“…Cell viability (%) was calculated by [(experimental absorbance À background absorbance)/(control absorbance À background absorbance)] Â 100. Cell viability at different concentrations of compounds was plotted and 50% inhibition of growth was calculated as IC 50 (Jiang et al, 2008).…”

7,7′′‐Dimethoxyagastisflavone‐induced Apoptotic or Autophagic Cell Death in Different Cancer Cells

“…The genus Taxus has been studied extensively for its taxoid compounds, particularly paclitaxel and its precursor 10‐deacetyl baccatin‐III. Many taxoids with antineoplastic, cytotoxic or antipromastigote activities have been isolated and investigated from the different organs of the Taxus genus (Chattopadhyay et al ., ; Dai et al ., ; Georgopoulou et al ., ; Jiang et al ., ).…”