The Diimide Drug PIPER has a Cytotoxic Dose-dependent Effect In Vitro and Inhibits Telomere Elongation in HELA Cells

• Published in: Anticancer research Vol. 25; no. 5; pp. 3341 - 3346
• Main Authors: PILLICH, R. T, SCARSELLA, G, GALATI, G, IZZO, L, IACOANGELI, A, CASTELLI, M, RISULEO, G
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01-09-2005
• Subjects: Biological and medical sciences; Dose-Response Relationship, Drug; HeLa Cells; Humans; Medical sciences; Perylene - analogs & derivatives; Perylene - pharmacology; Piperidines - pharmacology; Telomerase - antagonists & inhibitors; Telomere - drug effects; Telomere - metabolism; Tumors; Antineoplastic agent; Drug; Cytotoxicity; In vitro; Hela cell line; Telomere; TRAP assay; Cancerology; Inhibitor; Antitelomerase drug PIPER; Dose; cytotoxic effect; Elongation; Telomeric repeat amplification protocol assay
• ISSN: 0250-7005; 1791-7530

It is known that, in vitro, PIPER (N,N′-bis [2- (1-piperidino)ethyl] - 3,4,9,10- tetracarboxylic diimide) induces the formation
of the Hoogsteen quadruplex structure in telomere DNA, thus inhibiting the polymerisation of telomeric repeats. Since the
action of PIPER in vivo has been scarcely investigated, this study was addressed to gain some insight into the effects of
this drug on cultured HeLa cells. Vital staining with erythrosine, performed on cells exposed to different PIPER concentrations
(from 1 to 50 μM), showed that the drug exerts a dose-dependent cytotoxic effect, clearly evident after a short-term (24 h)
treatment. This early cytotoxic effect of PIPER on cultured HeLa cells was confirmed by a spectrophotometric/colorimetric
method employing methylthiazoletetrazolium (Mossmann assay). Hematoxylin/eosin staining of cells treated with PIPER for 24
h showed a nuclear condensation and a cytoplasmic vacuolisation, very pronounced at higher drug concentrations. These pictures
suggest that PIPER-induced cell death might be of the apoptotic type. Finally, the anti-telomerase activity of PIPER was monitored
by TRAP assay, performed on HeLa cell nuclear extracts treated with increasing drug concentrations. It was found that some
inhibition of telomerase is apparent even at low concentrations, while at the highest concentration the enzyme is completely
inhibited. These results indicate that the cytotoxic power of PIPER is possibly related to its antitelomeric effect.