Antiproliferative effects of mitoxantrone in ADR-sensitive and ADR-resistant P388 leukemia cells enhanced by vitamin K3.
Vitamin K3 was employed as a resistance-modifying agent to investigate its activity in enhancing mitoxantrone (MITO)-induced cytotoxicity in parental (P388/S) and multidrug resistant (P388/ADR) P388 leukemia cells. Vitamin K3 potentiated the antitumor effects of MITO in P388/S and P388/ADR tumor cells as monitored by inhibition of tumor cell survival (MTT assay). MITO and vitamin K3 in combination effected an enhanced inhibition of [3H]thymidine (DNA synthesis) and [3H]uridine (RNA synthesis) and also increased the life span of the sensitive and resistant tumor-bearing animals. The effect of vitamin K3 on the induction of DNA strand breaks by MITO was also examined. Increased fragmentation of DNA was illustrated in the sensitive and resistant P388 leukemia cells exposed to the combination. Observations indicate the restoration of sensitivity in P388/ADR cells to MITO by vitamin K3 that may be due to its ability to increase the MITO-induced DNA strand breaks.
Parekh
H
H
Chemotherapy Division, Cancer Research Institute, Tata Memorial Centre, Parel, Bombay, India.
Chavan
S
S
Chitnis
M
M
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects*; D004277:DNA, Single-Stranded / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D004357:Drug Synergism; D005260:Female; D007941:Leukemia P388 / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008942:Mitoxantrone / Q000494:pharmacology*; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014812:Vitamin K / Q000494:pharmacology*
D004273:DNA, Neoplasm; D004277:DNA, Single-Stranded; D012334:RNA, Neoplasm; D014812:Vitamin K; D004317:Doxorubicin; D008942:Mitoxantrone