A Pt(IV) Prodrug Combining Chlorambucil and Cisplatin: a Dual-Acting Weapon for Targeting DNA in Cancer Cells.
Diego MontagnerDina TolanEmma AndriolloValentina GandinCristina MarzanoPublished in: International journal of molecular sciences (2018)
In this study, two DNA-targeting agents, cisplatin and chlorambucil, were combined in a Pt(IV) prodrug, 1, which was thoroughly characterized by means of spectroscopic and spectrometric techniques. Tested towards a panel of various human tumor cell lines, this compound showed superior in vitro antitumor potential than the reference drug cisplatin. In addition, an antitumor potential of 1 was found, which is comparable to that of oxaliplatin in 3D spheroid models of colon cancer cells. Mechanistic studies performed in colon cancer cells confirmed that the conjugation of chlorambucil to Pt(IV) cisplatin-based scaffold tunes the lipophilicity of the prodrug, consequently improving the ability of the compound to accumulate into cancer cells and to target DNA, ultimately leading to apoptotic cancer cell death.
Keyphrases
- cancer therapy
- cell death
- circulating tumor
- cell free
- single molecule
- drug delivery
- endothelial cells
- drug release
- nucleic acid
- molecular docking
- papillary thyroid
- young adults
- emergency department
- circulating tumor cells
- cell proliferation
- liquid chromatography
- induced pluripotent stem cells
- signaling pathway
- mass spectrometry
- pluripotent stem cells
- lymph node metastasis
- drug induced
- childhood cancer