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Related Experiment Videos

Antitumor activity and cross-resistance studies with Pt-ascorbato complexes.

M Hrubisko1, E Balázová, F Kiss

  • 1Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Czechoslovakia.

Neoplasma
|January 1, 1989
PubMed
Summary

Two novel platinum complexes, AMA and CHA, demonstrate significant antitumor activity. The CHA complex shows efficacy comparable to DDP and TMA, with distinct cross-resistance patterns observed in cancer cell lines.

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Precision measurement and interpretation of inclusive

The European physical journal. C, Particles and fields·2018

Area of Science:

  • Medicinal Chemistry
  • Cancer Research
  • Pharmacology

Background:

  • Platinum-based chemotherapy, including cisplatin (DDP), is a cornerstone in cancer treatment.
  • Drug resistance remains a significant challenge, necessitating the development of new platinum complexes.
  • Ascorbate ligands offer a potential avenue for novel platinum drug design.

Purpose of the Study:

  • To evaluate the antitumor activity of two novel ascorbatoplatinum complexes: cis-diammineascorbatoplatinum(II) (AMA) and cis-bis(ascorbato)-trans-diaminocyclohexaneplatinum(II) (CHA).
  • To assess the efficacy of AMA and CHA against P388 leukemia in vivo and L1210 leukemia cell lines in vitro.
  • To investigate potential cross-resistance patterns between AMA, CHA, and established platinum drugs like DDP.

Main Methods:

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  • In vivo antitumor activity testing using P388 leukemia models.
  • In vitro cytotoxicity assays on sensitive and DDP-resistant L1210 leukemia cell lines (suspension culture and soft agar).
  • DNA synthesis inhibition assays to determine mechanism of action.
  • Comparative analysis with DDP and DACH-Pt(II)-4-carboxyphtalate (TMA).

    • Main Results:

    • Both AMA and CHA complexes exhibited significant antitumor activity in the experimental models.
    • The CHA complex demonstrated superior efficacy compared to AMA, with activity comparable to DDP and TMA.
    • Cross-resistance was observed between DDP and AMA, and between TMA and CHA.
    • Notably, no cross-resistance was found between DDP and CHA, or between TMA and AMA.

    Conclusions:

    • Ascorbato-platinum complexes, particularly CHA, represent promising candidates for novel anticancer agents.
    • The distinct cross-resistance profiles suggest potential for overcoming existing platinum resistance mechanisms.
    • Further investigation into CHA and AMA is warranted for clinical development against various cancers.