Antiproliferative activity and interactions with cell-cycle related proteins of the organotin compound triethyltin(IV)lupinylsulfide hydrochloride

Federica Barbieri, Fabio Sparatore, Monica Cagnoli, Cristina Bruzzo, Federica Novelli, Angela Alama

Research output: Contribution to journalArticle

Abstract

Organotin compounds, particularly tri-organotin, have demonstrated cytotoxic properties against a number of tumor cell lines. On this basis, triethyltin(IV)lupinylsulfide hydrochloride (IST-FS 29), a quinolizidine derivative, was synthesized and developed as a potential antitumor agent. This tin-derived compound exhibited potent antiproliferative effects on three different human cancer cell lines: teratocarcinoma of the ovary (PA-1), colon carcinoma (HCT-8) and glioblastoma (A-172). Cytotoxic activity was assessed by MTT and cell count assays during time course experiments with cell recovery after compound withdrawal. Significant cell growth inhibition (up to 95% in HCT-8 after 72 h of exposure), which also persisted after drug-free medium change, was reported in all the cell lines by both assays. In addition, the cytocidal effects exerted by IST-FS 29 appeared more consistent with necrosis or delayed cell death, rather than apoptosis, as shown by morphologic observations under light microscope, DNA fragmentation analysis and flow cytometry. In the attempt to elucidate whether this compound might affect genes playing a role in G1/S phase transition, the expressions of p53, p21WAF1, cyclin D1 and Rb, mainly involved in response to DNA-damaging stress, were analyzed by Western blot. Heterogeneous patterns of expression during exposure to IST-FS 29 were evidenced in the different cell lines suggesting that these cell-cycle-related genes are not likely the primary targets of this compound. Thus, the present data seem more indicative of a direct effect of IST-FS-29 on macromolecular synthesis and cellular homeostasis, as previously hypothesized for other organotin complexes.

Original languageEnglish
Pages (from-to)27-39
Number of pages13
JournalChemico-Biological Interactions
Volume134
Issue number1
DOIs
Publication statusPublished - Mar 14 2001

Fingerprint

Organotin Compounds
Cell Cycle Proteins
Cells
Cell Line
Proteins
Tin Compounds
Quinolizidines
Teratocarcinoma
Assays
cdc Genes
Genes
Cyclin D1
Phase Transition
G1 Phase
DNA Fragmentation
Glioblastoma
Tumor Cell Line
S Phase
Antineoplastic Agents
Flow cytometry

Keywords

  • Cell-cycle genes
  • Cytotoxicity
  • Tin compound
  • Tumor cell lines

ASJC Scopus subject areas

  • Toxicology

Cite this

Antiproliferative activity and interactions with cell-cycle related proteins of the organotin compound triethyltin(IV)lupinylsulfide hydrochloride. / Barbieri, Federica; Sparatore, Fabio; Cagnoli, Monica; Bruzzo, Cristina; Novelli, Federica; Alama, Angela.

In: Chemico-Biological Interactions, Vol. 134, No. 1, 14.03.2001, p. 27-39.

Research output: Contribution to journalArticle

Barbieri, Federica ; Sparatore, Fabio ; Cagnoli, Monica ; Bruzzo, Cristina ; Novelli, Federica ; Alama, Angela. / Antiproliferative activity and interactions with cell-cycle related proteins of the organotin compound triethyltin(IV)lupinylsulfide hydrochloride. In: Chemico-Biological Interactions. 2001 ; Vol. 134, No. 1. pp. 27-39.
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