Therapeutic Activity of Pretazettine, Standard Drugs, and the Combinations on Intraperitoneally Implanted Lewis Lung Carcinoma in Mice

Abstract

Therapeutic effectiveness of pretazettine (PTZ) has been demonstrated in the intraperitoneally (i.p.) implanted Lewis lung carcinoma (LLC) in both syngeneic and allogeneic mice. The i.p. implanted LLC has been found to be sensitive to most standard drugs tested such as cyclophosphamide (CY), actinomycin D, 5-fluorouracil, methotrexate, 6-thioguanine and vincristine, in comparison to the subcutaneously (s.c.) or intravenously (i.v.) implanted LLC which was reported to be resistant to most standard drugs (s.c.-LLC) or resistant to actinomycin D, methotrexate and vincristine (i.v.-LLC). The effectiveness of PTZ was comparable to that of standard drugs in the i.p. implanted LLC system, and the combination therapy of PTZ with these standard drugs except vincristine was synergistically or additively effective. Also, the PTZ combination rescued the allogeneic mice from the risk of adverse (tumor-enhancing) effects of CY at moderate doses (25–50 mg/kg) given therapeutically.

Anticancer Potential of Viva-Natural, a Dietary Seaweed Extract, on Lewis Lung Carcinoma in Comparison with Chemical Immunomodulators and on Cyclosporine-Accelerated AKR Leukemia

“…We found that therapeutic administration of CY at moderate doses (0.5-1 mg/mouse) enhanced the growth of LLC [3,4], Giraldi et al [8] also reported that the therapeutic administration of CY at. a daily low dose (0.3 mg/mouse/day x 8) resulted in increased lung metastasis of LLC.…”

“…Previously, we demonstrated that therapeutic ad ministration of cyclophosphamide (CY) at moderate doses (25-50 mg/kg) was not effective but promoted the growth of LLC [3,4], The adverse tumor-enhanc ing phenomenon was probably due to the strong im munosuppressive action of CY which overcame the cytoreductive action [4]. The antitumor activity of some cytotoxic drugs such as adriamycin, BCNU, actinomycin D, 5-FU, and methotrexate was almost abolished when CY was combined [4], Now, we have tested the antitumor effect of Viva-Natural in CYtreated mice and compared with two standard immu nomodulators, isoprinosine and MVE-2.…”

Anticancer Activity of a Natural Product, Viva-Natural, Extracted from <i>Undaria pinnantifida </i>on Intraperitoneally Implanted Lewis Lung Carcinoma

“…The optimal dose of standard cytotox ic drugs for combination in the intraperitoneally im planted LLC system has already been established [2], Immediately after a single intraperitoneal injection of standard drugs at optimal doses, daily injection of Viva-ppt at a dose of 50 mg/kg i.p. was commenced and continued for 7 days.…”

“…We have earlier described the isolation and charac terization of the active principles of narcissus bulbs [1,2] as a result of our screening plant materials of the Pacific area. Now we have found an agent active against Lewis lung carcinoma (LLC) present in Un daria pinnantifida, a popular dietary seaweed.…”

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

“…During antiviral screening of medicinal plants of the Pacific area, we found pre tazettine hydrochloride (PTZ), a narcissus alkaloid, to be active against Rauscher vi ral leukemia and spontaneous AKR leu kemia [1,2], PTZ is a specific inhibitor of cellular protein synthesis and is also effec tive against intraperitoneally implanted Lewis lung carcinoma (LLC) and Ehrlich ascites tumor, both non-viral transplan table tumors [3,4], In contrast to the intraperitoneally implanted LLC, which is moderately sensitive to many standard cytotoxic drugs [3], LLC implanted subcu taneously in the syngeneic or semi-syn geneic mice is highly resistant to chemo therapy [5,6]. This paper describes the ef fectiveness of PTZ, standard drugs, and combinations of both, against the subcu taneously implanted LLC in syngeneic and allogeneic mice.…”