Antitumor action of sophoridine
Abstract
Sophoridine, an alkaloid isolated from Sophora alopecuroides L., is a new anticancer compound. The transplanted tumors of Lewis Lung carcinoma, S 180, U 14 and EC were inhibited 30-60% (p<0.05) by sophoridine with smaller therapeutic dose (10 mg/kg ig) than that of sophocarpine (60 mg/kg ig).
The acute ip and iv LD in mice were 60+0.1 and 50.4+0.4 mg/kg respectively. In dog iv 5 mg/kg×35 d produced no apparant toxicity except mild reversible leukopenia and thrombopenia in large dose (10 mg/kg×35 d).
When normal mice or mice bearing S 180. U 14 solid tumors were given ig sophoridine 20 mg/kg qd×10 d, the contents of RNA and DNA in tumor and spleen decreased slightly. Sophoridine showed no marked influence on the content of cAMP in S 180 solid tumor. The mitochondria of S 180 sarcoma cells swelled and dissolved, vacuolations were formed inside the cytoplasma of the tumor cells. The microvilli of the cell membrane diminished.
After iv a single dose (40 mg/kg) of sophoridine, the plasma concentration showed an initial rapid drop and subsequent declination and were rapidly taken up by various organs, highest in kidney, moderate in spleen and lung, and lowest in plasma and brain; 29% of the injected sophoridine was excreted within 24 h in urine.
Sophoridine showed no influence on immunity during the studies on T-lymphocyte Anae reaction of blood smear and concomitant tumor immunity in mice.
Our experiments showed that the matrinoid alkaloids, sophoridine and sophocarpine possess noticeable antitumor activity.
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The acute ip and iv LD in mice were 60+0.1 and 50.4+0.4 mg/kg respectively. In dog iv 5 mg/kg×35 d produced no apparant toxicity except mild reversible leukopenia and thrombopenia in large dose (10 mg/kg×35 d).
When normal mice or mice bearing S 180. U 14 solid tumors were given ig sophoridine 20 mg/kg qd×10 d, the contents of RNA and DNA in tumor and spleen decreased slightly. Sophoridine showed no marked influence on the content of cAMP in S 180 solid tumor. The mitochondria of S 180 sarcoma cells swelled and dissolved, vacuolations were formed inside the cytoplasma of the tumor cells. The microvilli of the cell membrane diminished.
After iv a single dose (40 mg/kg) of sophoridine, the plasma concentration showed an initial rapid drop and subsequent declination and were rapidly taken up by various organs, highest in kidney, moderate in spleen and lung, and lowest in plasma and brain; 29% of the injected sophoridine was excreted within 24 h in urine.
Sophoridine showed no influence on immunity during the studies on T-lymphocyte Anae reaction of blood smear and concomitant tumor immunity in mice.
Our experiments showed that the matrinoid alkaloids, sophoridine and sophocarpine possess noticeable antitumor activity.