0000000000243091
AUTHOR
Florence Bouyer
Chemotherapy overcomes TRAIL-R4-mediated TRAIL resistance at the DISC level
International audience; TNF-related apoptosis-inducing ligand or Apo2L (Apo2L/TRAIL) is a promising anti-cancer drug owing to its ability to trigger apoptosis by binding to TRAIL-R1 or TRAIL-R2, two membrane-bound receptors that are often expressed by tumor cells. TRAIL can also bind non-functional receptors such as TRAIL-R4, but controversies still exist regarding their potential to inhibit TRAIL-induced apoptosis. We show here that TRAIL-R4, expressed either endogenously or ectopically, inhibits TRAIL-induced apoptosis. Interestingly, the combination of chemotherapeutic drugs with TRAIL restores tumor cell sensitivity to apoptosis in TRAIL-R4-expressing cells. This sensitization, which ma…
Tumor cells can escape DNA-damaging cisplatin through DNA endoreduplication and reversible polyploidy
Cancer chemotherapy can induce tumor regression followed, in many cases, by relapse in the long-term. Thus this study was performed to assess the determinants of such phenomenon using an in vivo cancer model and in vitro approaches. When animals bearing an established tumor are treated by cisplatin, the tumor initially undergoes a dramatic shrinkage and is characterized by giant tumor cells that do not proliferate but maintain DNA synthesis. After several weeks of latency, the tumor resumes its progression and consists of small proliferating cells. Similarly, when tumor cells are exposed in vitro to pharmacological concentrations of cisplatin, mitotic activity stops initially but cells main…
cis-Dichloroplatinum(II) complexes tethered to dibenzo[c,h][1,6]naphthyridin-6-ones: Synthesis and cytotoxicity in human cancer cell lines in vitro
A novel family of cisplatin-type complexes tethered to dibenzo[c,h][1,6]naphthyridin-6-one topoisomerase inhibitor via a polymethylene chain and their nonplatinated counterparts were prepared. Their potential cytotoxicity was assessed in three human colorectal cancer cell lines HCT 116, SW480 and HT-29 and compared to the reference molecules cisplatin and oxaliplatin. Platinated compounds were poorly active whilst nonplatinated dibenzo[c,h][1,6]naphthyridin-6-one moieties exhibited higher cytotoxic properties than cisplatin and oxaliplatin whatever the length of the polymethylene chain; molecules containing the tri- and hexamethylene chain length were the most cytotoxic.
Optimization of MCM-41 type silica nanoparticles for biological applications: Control of size and absence of aggregation and cell cytotoxicity
Abstract Mesoporous silica nanoparticles were synthesized at high pH using CTAB as a template and TEOS as a silica precursor. It was shown that varying the NaOH concentration between 5 and 27.5 mM allows the size, pore and silica structure of mesoporous nanoparticles to be precisely tuned. In particular, monodisperse nanoparticles with the MCM-41 structure with size ranging from 90 nm to 450 nm were obtained by increasing the NaOH concentration from 12.5 to 22.5 mM. It thus demonstrates that NaOH concentration must range between 12.5 and 15 mM in order to prepare MCM-41 silica nanoparticles with optimal size for nanovectorization. We also found that under usual conditions the aggregation of…