Telomerase inhibition is a specific early event in salvicine-treated human lung adenocarcinoma A549 cells

The Telomeric Protein TRF2 Is Critical for the Protection of A549 Cells from Both Telomere Erosion and DNA Double-Strand Breaks Driven by Salvicine

“…We reported previously that SAL elicited DNA DSBs (Meng and Ding, 2001;Meng et al, 2001a,b;Lu et al, 2005a) and telomere erosion (Liu et al, 2004) in separate systems. In the present study, using a single system in which SAL did not induce early apoptosis (data not shown), we found that there exists a common cellular response mechanism to both DNA DSBs and telomere erosion in SAL-initiated events (i.e., SAL concurrently elicited both genomic DNA DSBs and telomere erosion in A549 cells).…”

“…Telomeric DNA in ChIP (%) ϭ Telomeric DNA signals of ppt/Telomeric DNA signals of input ϫ 100%. at ASPET Journals on May 10, 2018 molpharm.aspetjournals.org SAL inhibited telomerase activity after short-term treatment, it is obviously not the main factor to shorten telomere within 3 h (Liu et al, 2004). Moreover, the colocalization of DNA damage signals and telomere signals showed that the DNA damage signals at the sites of telomeres increased with the concentrations of SAL (Fig.…”

“…Relative telomere length was detected by flow cytometry (flow-FISH) via fluorescence in situ hybridization with a fluorescein-conjugated PNA probe using the Telomere PNA Kit/FITC for Flow Cytometry (Dako Denmark A/S, Glostrup, Denmark) according to the manufacturer's protocol with a slight modification (Liu et al, 2004). Relative telomere length was the ratio of the telomere fluorescence intensity in treated cells to that in the control; the telomere fluorescence intensity ϭ (Mean FL1 with probe Ϫ mean FL1 without probe).…”

“…Moreover, SAL stimulates intracellular reactive oxygen species, which subsequently elicit DNA DSBs closely related with cell death (Lu et al, 2005b). Furthermore, SAL inhibits telomerase activity and shortens telomere length in a telomerase-independent manner (Liu et al, 2002(Liu et al, , 2004. Because of the notion that the telomere erosion is critical for DNA DSBs, we have investigated whether tumor cells share the common response to telomeric and nontelomeric DNA damage upon exposure to salvicine.…”

Can CYP1A1 siRNA be an effective treatment for lung cancer?

“…In addition, there may be limited application for this strategy to succeed in treating lung cancer due to difficulties in administering and targeting siRNA. A549 is found to express telomerase and several CYP forms including CYP1A1 and possesses metabolic activities toward xenobiotics [21][22]. Furthermore, A549 cell line is known to retain several characteristics of human lung epithelial cell CYP expression, which makes it a valuable model for mechanistic studies on the induction of the pulmonary CYP system [21][22][23].…”