Therapeutic Potentials of Pretazettine, Standard Anticancer Drugs, and Combinations on Subcutaneously Implanted Lewis Lung Carcinoma

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Abstract
We reported previously that pretazettine hydrochloride (PTZ), a narcissus alkaloid, was found to be active against intraperitoneally implanted Lewis lung carcinoma. The therapeutic effectiveness of PTZ has now been investigated on the subcutaneously implanted Lewis lung carcinoma (LLC) which is a representative tumor, resistant to hcemotherapy in mice. In syngeneic mice, PTZ therapy was inhibitory to the pulmonary metastasis although it was not effective on prolonging the life span of mice nor inhibitory to the growth of primary tumor implanted on the back of the mice. In allogeneic DBA/2 mice, PTZ was inhibitory to the pulmonary metastasis and also prolonged the life span. In allogeneic BALB/c mice, PTZ increased the number of tumor-free survivors. In syngeneic mice, combination of PTZ with standard cytotoxic drugs such as adriamycin, cis-diamminedichloroplatinum, 5-fluorouracil, methotrexate, or vincristine was found to be active against the subcutaneously implanted LLC. These agents were not effective when administered individually. The activity of cyclophosphamide was increased by a combination with PTZ. The combination of PTZ plus 6-thioguanine was not active. Standard cytotoxic drugs, except methotrexate and 6-thioguanine, were found to be active against subcutaneously implanted LLC in allogeneic DBA/2 mice (not in syngeneic mice) when administered individually. PTZ was also found to be active against subcutaneously implanted LLC in the tails in syngeneic mice on prolonging the life span.