DIFFERENTIAL KILLING EFFICACY OF 20 ANTI-TUMOR DRUGS ON PROLIFERATING AND NON-PROLIFERATING HUMAN-TUMOR CELLS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (6) , 2328-2333
Abstract
The lethal effects of a 1-h treatment with 20 antitumor drugs on proliferating and nonproliferating cultured human colon carcinoma cells (line LoVo) were analyzed quantitatively by the colony-forming technique. Proliferating cells were obtained from exponentially growing cultures, while nonproliferating cells were from cultures in a stationary phase of growth. The 1-h treatment was intended to approximate serum peak levels after bolus administration. Two agents, cis-platinum and vindesine, were more effective on nonproliferating than on proliferating cells. Mitomycin C, nitrosoureas and dihydroxybisalkylanthracenedione were equally effective on proliferating and nonproliferating cells. The low lethal activity (< 1 log) of methylglyoxal bis(guanylhydrazone), hycanthone and vinblastine was similar in proliferating and nonproliferating cells. For most drugs (adriamycin, rubidazone, bleomycin, maytansine, vincristine, epipodophyllotoxin, fluorouracil, hydroxyurea, methotrexate and trans-plantinum) cytotoxicity was significantly less pronounced (or even totally absent) in nonproliferating than in proliferating cells. The significance of cellular proliferation kinetics in determining sensitivity to antitumor therapy is demonstrated. Nonproliferating human cells have decreased sensitivity to most antitumor agents. An occasional agent may present increased activity to nonproliferating cells; but at best, few agents can be expected to be as effective on nonproliferating as on proliferating cells.