Sixty-three tannins and related polyphenols were intraperitoneally injected into mice at 4 d before intraperitoneal sarcoma-180 cell inoculation, and their antitumor activities were evaluated. The condensed tannins and related compounds all showed negligible activity. As regards the hydrolyzable tannins, active compounds were found among ellagitannins. In particular, dimeric ellagitannins such as oenothein B, rugosin E, rugosin D, gemin A and coriariin A showed significantly higher antitumor activity than agrimoniin, which we previously reported as an antitumor tannin. Coriariin A, which has four galloyl groups instead of two hexahydroxydiphenoyl groups of agrimoniin, showed the strongest activity. It seems to be essential for marked antitumor activity that ellagitannins should possess a dimeric structure with several galloyl groups on the glucose core.
Abstract-The effect of agrimoniin, a tannin contained in Agrimonia pilosa LEDEB., on ascites type and solid type rodent tumors was investigated.When agrimoniin was intraperitoneally (i.p.) administered at dosages over 10 mg/kg before or after the MM2 cell i.p. inoculation, this tannin almost completely rejected the tumor growth in the mice. This tannin prolonged the life span of mice bearing MM2 or cured by the intravenous or per oral pre or postmedication.Agrimoniin also inhibited the growth of MH1 34 and Meth-A solid type tumors.Agrimoniin showed strong cytotoxicity on MM2 cells in vitro, but the activity was diminished to about 4% of the initial activity by the addition of fetal calf serum to the culture.On the other hand, i.p. injection of agrimoniin increased the number of peripheral white blood cells and the ratio of monocytes.On the 4th day after the i.p. injection of the tannin, cytotoxic adherent peritoneal exudate cells were also increased. The spleen of the mice was enlarged, and the spleen cells possessed the capacity to take up 3H-thymidine.Agrimoniin showed weak direct migration activity against spleen cells from non-treated mice. These results indicate that agrimoniin is a potent antitumor tannin and suggest that the antitumor effect may be due to this tannin enhancing the immune response of the host animals through the actions on tumor cells and some immunocytes.
The cytotoxic activities of the PEC after an i.p. injection of agrimoniin, a tannin contained in Agrimonia pilosa Ledeb. were studied. The plastic nonadherent PEC had significantly higher NK cell activity than the untreated control, and the adherent PEC were cytostatic toward MM2 and MH134 cells. The adherent PEC did not cause tumor cell lysis by themselves, but were cytolytic against MM2 cells in the presence of anti-MM2 sera. In the course of these effects of PEC after the i.p. injection of agrimoniin, the augmentation of NK cell activity was the earliest reaction, reaching a peak at 2 days after the injection; then, cytostatic activity increased. The induction of antibody-dependent cell lytic activity was a later reaction, which reached a peak at 6 days after the injection.
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