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-diaminecyclohexaneplatinum (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.