TY - JOUR
T1 - A Pt(IV) prodrug combining chlorambucil and cisplatin
T2 - A dual-acting weapon for targeting DNA in cancer cells
AU - Montagner, Diego
AU - Tolan, Dina
AU - Andriollo, Emma
AU - Gandin, Valentina
AU - Marzano, Cristina
N1 - Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2018/12
Y1 - 2018/12
N2 - 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.
AB - 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.
KW - Chlorambucil
KW - Cisplatin
KW - Cytotoxicity
KW - Pt(IV) prodrugs
UR - http://www.scopus.com/inward/record.url?scp=85057530081&partnerID=8YFLogxK
U2 - 10.3390/ijms19123775
DO - 10.3390/ijms19123775
M3 - Article
C2 - 30486477
AN - SCOPUS:85057530081
SN - 1661-6596
VL - 19
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 12
M1 - 3775
ER -
