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.
Get full access to this article
View all access options for this article.
References
1.
BanskuliI., YinM.B., MazzoniA., AbdellahA.J.M., RustumY.M.: Enhancement of adriamycin-induced cytotoxicity by increased retention and inhibition of DNA repair in Dox-resistant P388 cell lines with new channel blocker DMDP. Anticancer Res., 9: 567–574, 1989.
2.
BegleiterA.: Cytocidal action of the quinone group and its relationship to antitumor activity. Cancer Res., 43: 481–484, 1983.
3.
BellamyW.T., DaltonW.S., KaileyJ.M., GleasonM.C., McCloskeyT.M., DorrR.T., AlbertsD.S.: Verapamil reversal of doxorubicin resistance in multidrug resistant human myeloma cells and association with drug accumulation and damage. Cancer Res., 48: 6365–6370, 1988.
4.
BoawdenG.T., AlbertsD.S., RobertR., PengY-M., GarciaD.: Comparative molecular pharmacology in leukemic L1210 cells of anthracene anticancer drugs, mitoxantrone and bisantrene. Cancer Res., 45: 4915–4920, 1985.
BrownF.U., KleinM., KandaswamyT.S., MandelH.G.: Rapid membrane filtration technique for studying action of 6-thioguanine on tumor cells in vitro. Cancer Res., 23: 254–259, 1963.
7.
BurnsC.P.: Membranes and cancer chemotherapy. Cancer Invest., 6: 439–451, 1988.
8.
CarterS.D.: Adriamycin: A review. J. Natl. Cancer Inst., 55: 1265–1274, 1975.
9.
ChabnerB.A., FojoA.: Multidrug resistance: P-glycoprotein and its allies - the elusive foes. J. Natl. Cancer Inst., 81: 910–913, 1989.
10.
ChitnisM.P., ParekhH.K., SatyamoorthyK.: Differential effect of Clofibrate on adriamycin cytotoxicity in P388 murine leukemia cells sensitive and resistant to adriamycin. Tumori, 75: 100–105, 1989.
11.
CleaverJ.E.: Handbook of mutagenicity test procedures.KilboyB.J., LegatorM., WicolsW. (Eds.), pp. 19–24, Elsevier, New York, 1977.
12.
ColeS.P.C., DownesH.F., MirskiS.E.L., ClementsD.J.: Alterations in glutathione and glutathione-related enzymes in a multidrug resistant small cell lung cancer cell line. Mol. Pharmacol., 37: 192–197, 1990.
13.
DeffieA.M., AdamT., SeneviratneC., BeenkenS.W., BatraJ.W., SheaT.C., HennerW.D., GoldenbergG.J.: Multifactorial resistance to adriamycin: Relationship to DNA repair, glutathione transferase activity, drug efflux and P-glycoprotein in cloned cell lines of adriamycin-sensitive and -resistant P388 leukemia. Cancer Res., 48: 3559–3602, 1988.
14.
DeffieA.M., BatraJ.K., GoldenbergG.F.: Direct correlation between topoisomerase II activity and cytotoxicity in adriamycin-sensitive and -resistant P388 leukemia cell lines. Cancer Res., 49: 58–62, 1989.
15.
DeucharsK.L., LingV.: P-glycoprotein and multidrug resistance in cancer chemotherapy. Semin. Oncol., 16: 156–165, 1989.
16.
EndicottJ.A., LingV.: The biochemistry of P-glycoprotein-mediated multidrug resistance. Ann. Rev. Biochem., 58: 137–171, 1989.
17.
GoldsteinL.J., GalskiH., FojoA., WillinghamM., LaiS-L., GazdarA., PirkerR., GreenA., CristW., BrodeurG.M., LieberM., CossmanJ., GottesmanM.M., PastanI.: Expression of a multidrug resistance gene in human cancers. J. Natl. Cancer Inst., 81: 116–124, 1989.
18.
GottesmanM.M., PastanI.: The multidrug transporter, a double edged sword. J. Biol. Chem., 263: 12163–12166, 1988.
19.
JohnsonR.K., ChitnisM.P., EmbreyW.M., GregoryE.B.: In vivo characteristics of resistance and cross-resistance of adriamycin resistant subline of P388 leukemia. Cancer Treat. Rep., 62: 1535–1547, 1978.
20.
JohnsonR.K., Zee-ChengR.K.Y., LeeW.W., ActonE.M., HenryD.W., ChengC.C.: Experimental antitumor activity of aminoanthraquinones. Cancer Treat. Rep., 63: 425–439, 1979.
21.
KramerR.A., ZakherJ., KimG.: Role of glutathione redox cycle in acquired and de novo multidrug resistance. Science, 241: 694–697, 1988.
22.
LownJ.W., MorganA.R., YenS.F., WangY.H., WilsonW.D.: Characteristics of binding of the anticancer agents mitoxantrone and amentantrone and related structures to deoxyribonucleic acids. Biochemistry, 24: 4028–4035, 1985.
23.
LutzkyJ., AstorM.B., TaubR.N., BakerM.A., BhallaK., GervasoniJ.R., RosadoM., StewartV., KrishnaS., HindenburgA.A.: Role of glutathione and dependent enzymes in anthracycline-resistant HL60/AR cells. Cancer Res., 49: 4120–4125, 1989.
24.
Ming-BiaoY., BanskuliI., FrankC., RustumY.M.: Modulation of doxorubicin-induced DNA lesions by verapamil, DMDP and dipyridamole in resistant P388 cell lines. Anticancer Res., 10: 327–332, 1990.
25.
NicoteraP., MooreM., MirabelliF., BellomoG., OrreniusS.: Inhibition of hepatocyte plasma membrane Ca+2-ATPase activity by menadione metabolism and its restoration by thiols. FEBS Lett., 181: 149–153, 1985.
26.
ParekhH.K., ChitnisM.P.: Evaluation of quinidine effects on the antitumor activity of adriamycin and mitoxantrone in adriamycin-sensitive and -resistant P388 leukemia cells. Selective Cancer Therapeutics, 6: 93–101, 1990.
27.
ParekhH.K., ChitnisM.P.: Effect of alteration in permeability by non-ionic surfactants on adriamycin cytotoxicity in murine tumor models in vitro. Oncology, 47: 501–507, 1990.
28.
ParekhH.K., Mansuri-TorshiziH., SrivastavaT.S., ChitnisM.P.: Circumvention of adriamycin resistance: Effect of 1,4-naphthoquinone (vitamin K3) on drug cytotoxicity in sensitive and MDR P388 leukemia cells. Cancer Lett. (in press), 1992.
RamuA., GlaubigerD., MagrathI., JoshiA.: Plasma membrane lipid structural order in doxorubicin-sensitive and -resistant P388 cells. Cancer Res., 43: 5533–5537, 1983.
31.
ShenJ., HughesC., ChaoC., CaiC., BartelsC., GessnerT., SubjeckJ.: Coinduction of glucose-regulated proteins and doxorubicin resistance in Chinese hamster cells. Proc. Natl. Acad. Sci. (USA), 84: 3278–3282, 1987.
32.
SmithI.E.: Mitoxantrone (novantrone), a review of experimental and early clinical studies. Cancer Treat. Rep., 10: 103–115, 1983.
33.
TaperH.S.: Reversibility of acid and alkaline deoxyribo-nucleases deficiency in malignant tumor cells. J. Histochem. Cytochem., 29: 1053–1060, 1981.
TsuruoT.: Mechanisms of multidrug resistance and implications for therapy. Jpn. J. Cancer Res., 79: 285–296, 1988.
36.
van der BleikA., BorstP.: Multidrug resistance. Adv. Cancer Res., 52: 165–203, 1989.
37.
WeinsteinR.S., KuszakJ.R., KluskensL.F., CoonJ.S.: P-glycoproteins in pathology: The multidrug resistance family in humans. Human Pathol., 21: 34–48, 1990.
