Synergistic inhibition of growth and induction of apoptosis by 8- chloro-cAMP and paclitaxel or cisplatin in human cancer cells

Giampaolo Tortora, Giuditta Di Isernia, Claudia Sandomenico, Roberto Bianco, Grazia Pomatico, Stefano Pepe, A. Raffaele Bianco, Fortunato Ciardiello

Research output: Contribution to journalArticle

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Abstract

8-Chloro-cAMP (8-Cl-cAMP) is novel agent that is able to inhibit the growth of a wide variety of cancer cell types in vitro and in vivo and, at doses devoid of toxicity, to achieve plasma concentrations in cancer patients in a range effective for cancer cell growth inhibition. In this study, we have demonstrated that 8-Cl-cAMP, at a dose causing mild or no growth inhibition, synergistically increased the growth-inhibitory effect of paclitaxel or cisplatin in a wide series of cell lines including human breast, lung, ovary, colon, and head carcinomas and melanoma. A similar effect was also observed with another taxane, docetaxel, and with the platinum-derivative carboplatin, 8-Cl-cAMP also markedly enhanced apoptotic cell death induced by each cytotoxic drug. A cooperative antitumor effect was also observed in vivo, because treatment with paclitaxel followed by 8-Cl- cAMP markedly inhibited the growth of GEO human colon cancer xenografts as compared to paclitaxel alone without signs of toxicity. These data demonstrate that 8-Cl-cAMP synergistically increases the antiproliferative activity of taxanes and platinum-derived compounds and provide a rationale to use 8-Cl-cAMP in combination with taxanes and platinum derived compounds.

Original languageEnglish
Pages (from-to)5107-5111
Number of pages5
JournalCancer Research
Volume57
Issue number22
Publication statusPublished - Nov 15 1997

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Apoptosis
Growth
Platinum Compounds
Taxoids
Neoplasms
docetaxel
Paclitaxel
Carboplatin
Platinum
Heterografts
Colonic Neoplasms
TP protocol
8-chloro-cyclic adenosine monophosphate
Ovary
Melanoma
Colon
Breast
Cell Death
Head
Carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Tortora, G., Di Isernia, G., Sandomenico, C., Bianco, R., Pomatico, G., Pepe, S., ... Ciardiello, F. (1997). Synergistic inhibition of growth and induction of apoptosis by 8- chloro-cAMP and paclitaxel or cisplatin in human cancer cells. Cancer Research, 57(22), 5107-5111.

Synergistic inhibition of growth and induction of apoptosis by 8- chloro-cAMP and paclitaxel or cisplatin in human cancer cells. / Tortora, Giampaolo; Di Isernia, Giuditta; Sandomenico, Claudia; Bianco, Roberto; Pomatico, Grazia; Pepe, Stefano; Bianco, A. Raffaele; Ciardiello, Fortunato.

In: Cancer Research, Vol. 57, No. 22, 15.11.1997, p. 5107-5111.

Research output: Contribution to journalArticle

Tortora, G, Di Isernia, G, Sandomenico, C, Bianco, R, Pomatico, G, Pepe, S, Bianco, AR & Ciardiello, F 1997, 'Synergistic inhibition of growth and induction of apoptosis by 8- chloro-cAMP and paclitaxel or cisplatin in human cancer cells', Cancer Research, vol. 57, no. 22, pp. 5107-5111.
Tortora, Giampaolo ; Di Isernia, Giuditta ; Sandomenico, Claudia ; Bianco, Roberto ; Pomatico, Grazia ; Pepe, Stefano ; Bianco, A. Raffaele ; Ciardiello, Fortunato. / Synergistic inhibition of growth and induction of apoptosis by 8- chloro-cAMP and paclitaxel or cisplatin in human cancer cells. In: Cancer Research. 1997 ; Vol. 57, No. 22. pp. 5107-5111.
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