Zoledronic acid overcomes chemoresistance by sensitizing cancer stem cells to apoptosis

WOS: 000432895500002PubMed ID: 29300112Unlike low tumorigenic bulk tumor cells (non-CSCs), cancer stem cells (CSCs) are a subset of tumor cells that can self-renew and differentiate into different cancer subtypes. CSCs are considered responsible for tumor recurrence, distant metastasis, angiogenesis, and drug or radiation resistance. CSCs also are resistant to apoptosis. Zoledronic acid (ZA) is a third generation bisphosphonate that reduces cell proliferation and exhibits anti-tumor effects by inducing cell death in some malignancies; however, the effects of ZA on CSCs are unclear. We investigated the anti-cancer effects of ZA on two epithelial cancer cell lines, prostate DU-145 and breast MCF7, focusing primarily on induction and activation of apoptosis. Cluster of differentiation (CD) 133(+)/CD44(+) prostate CSCs and CD 44(+)/CD24 breast CSCs were isolated from the DU-145human prostate cancer and MCF-7 human breast cancer cell lines, respectively, using FACSAria flow cytometry cell sorting. CSCs and non-CSCs were exposed to increasing concentrations of ZA for 24, 48 and 72h to determine the IC50 dose. Annexin-V assay for detecting cell death and cell cycle was performed using the Muse Cell Analyzer. Prostate CSCs and non-CSCs were assayed by quantitative reverse transcription PCR (qRT-PCR) array for detecting 84 key apoptosis related genes. Gene regulation at the protein level was investigated by immunofluorescence. ZA caused a dose- and time-dependent decrease in cell viability. Treatment with ZA resulted in a concomitant increase in apoptosis and cell cycle arrest at S-phase in CSCs. Significant over/under-expressions were detected in seven of the genes of ZA-treated DU-145 CSCs cells. Expressions of CASP9, CASP4, BAX and BAD genes increased, while the expressions of BIRC3, BIRC2 and BCL2 genes decreased. In the DU-145 non-CSCs, five genes exhibited changes in gene expression after ZA treatment, two exhibited increased expression (CASP7 and BAD) and three exhibited decreased expression (BIRC3, BIRC2 and BCL2). ZA caused cell death of drug resistant breast MCF-7 and prostate DU-145 cancer stem cells by activating apoptosis. ZA can facilitate the intrinsic pathway of apoptosis in human prostate CSCs by down-regulating anti-apoptotic genes and up-regulating pro-apoptotic genes. ZA may be an effective therapeutic agent for targeting chemoresistance in CSCs

Targeting apoptosis resistance in cancer stem cells by the biphosphonate zoledronic acid

41st FEBS Congress on Molecular and Systems Biology for a Better Life -- SEP 03-08, 2016 -- Kusadasi, TURKEYWOS: 000383616900278FEB

The interaction of artificial saliva with heat-pressed all-ceramic materials.

1st Annual Meeting of the International-Association-for-Dental-Research -- SEP 18, 2002 -- Cardiff, WALESWOS: 00018907830294

Determination of elemental composition of substance lost following wear of all-ceramic materials

WOS: 000183116000009PubMed ID: 12854789Purpose: The aim of this study was to test the possible elemental release of four different all-ceramic materials in a wear machine to predict results about their long-term behavior in the oral environment. Materials and Methods: Four different all-ceramic materials with different chemical compositions were selected for the wear testing. A total of 20 cylindric samples, five for each ceramic group, were prepared according to the manufacturers' instructions. These were subjected to two-body wear testing in an artificial saliva medium under a covered unit with a computer-operated wear machine. The artificial saliva Solutions for each material were analyzed for the determination of amounts of sodium, potassium, calcium, magnesium, and lithium elements released from the glass-ceramic materials. The differences between and within groups were statistically analyzed with a one-way ANOVA, followed by Duncan tests. Results: The statistical analyses revealed no significant differences among Na, K, Ca, or Mg levels (P greater than or equal to .05) released from the leucite-reinforced groups, while there was a significant (P < .05) increase in Li release from the lithium disilicate group. Conclusion: Considerable element release to the artifical saliva medium was demonstrated in short-term wear testing. The lithia-based ceramic was more prone to Li release when compared with other elements and materials

Comparative assessment of the diagnostic value of neopterin and acute phase proteins in angiographically assessed stable coronary artery disease

WOS: 000221890100005Assessment of markers of systemic inflammation, such as acute-phase reactants C-reactive protein (CRP), fibrinogen and ceruloplasmin, sialic acid, a major component of these proteins and neopterin, a specific marker of cellular immune activation, in clinically stable coronary artery disease, may contribute to staging and risk stratification. These markers were measured in 225 consecutive stable coronary artery disease patients before undergoing coronary angiography. According to their angiographic scores 32 patients were designated as having minor, 34 moderate and 96 severe coronary artery disease. 63 patients with negative angiograms were taken as the anglographic controls. High sensitive-CRP (hs-CRP) and fibrinogen were found to be higher in patients with angiographically established coronary artery disease, than in angiographic controls (p < 0.05) and correlated with the severity and extent of disease. Ceruloplasmin and sialic acid concentrations did not differ between patients with and without angiographically established coronary artery disease. Serum neopterin levels were sigificantly higher in patients undergoing coronary angiography than in healthy controls. Neopterin levels were similar between the different subgroups of coronary artery disease, suggesting that neopterin determinations do not contribute to the assessment of the presence and severity of disease in clinically stable patients. In stable angina, serum hs-CRP and plasma fibrinogen levels proved to be more effective than ceruloplasmin, sialic acid and neopterin in discriminating between patients with positive and negative angiograms and various degrees of coronary artery disease, thus in pointing out to increased risk. Our results, do not support the inclusion of neopterin in risk assessment of stable coronary artery disease