Cellular accumulation and DNA damage induced by liposomal cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexaneplatinum+ ++(II) in LoVo and LoVo/PDD cells.
Liposomal cis-bis-neodecanato-trans-R,R-1,2-diaminocyclohexaneplatinum (11) (L-NDDP) is a liposome-entrapped platinum complex that has shown partial lack of cross-resistance with cisplatin in human colon carcinoma LoVo cells. We studied the drug accumulation and DNA damage induced by L-NDDP and cisplatin in LoVo and LoVo/PDD cells. Our results indicate that the accumulation of L-NDDP in LoVo cells is several-fold higher than that of cisplatin; that the accumulation of L-NDDP is similar in both cell lines, whereas that of cisplatin is reduced by 2- to 3-fold in LoVo/PDD cells; and that the transmembrane transport of cisplatin is highly dependent on temperature while that of L-NDDP is not. We also found that the cytotoxicity of both agents correlates with the extent of DNA-protein cross-link formation, and that DNA interstrand cross-linking does not appear to play a role in the cytotoxicity of L-NDDP, whereas it correlates with cisplatin cytotoxicity.
Han
I
I
Department of Thoracic/Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Nguyen
T
T
Yang
L Y
LY
Khokhar
A R
AR
Perez-Soler
R
R
D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000493:pharmacokinetics / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D004337:Drug Carriers; D006801:Humans; D008081:Liposomes; D009363:Neoplasm Proteins / Q000187:drug effects / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D013696:Temperature; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D004273:DNA, Neoplasm; D004337:Drug Carriers; D008081:Liposomes; D009363:Neoplasm Proteins; D009944:Organoplatinum Compounds; C054367:bis-neodecanoato-1,2-diaminocyclohexaneplatinum(II); D002945:Cisplatin