aconitine and Neoplasm-Metastasis

The objective of the study was the investigation of anticancer activity of aconitine-containing herbal extract BC1 against two tumor strains with different metastatic potency: strongly metastatic Lewis lung carcinoma (LLC) and its weakly metastatic counterpart (LLC-R9).. It was shown that low proliferative activity and high metastatic potential of LLC correlated with high refractoriness of this tumor to BC1 action, while significant inhibition of tumor growth and metastasis by BC1 were observed against actively proliferating and weakly metastatic LLC-R9. Maximal antitumor activity of BC1 (> 70% of inhibition of primary tumor growth) and antimetastatic action (88% of metastatic inhibition) were observed at the dose of MTD/20. High efficacy of BC1 against LLC-R9 was shown to be accompanied by 2-fold increase of apoptosis rate predominantly in diploid cells.. The obtained results showed the ability of aconitine-containing herbal extract BC1 to inhibit growth of primary tumor and metastases of actively proliferating and weakly metastatic variant of Lewis lung carcinoma.

Topics: Aconitine; Adjuvants, Immunologic; Animals; Apoptosis; Carcinoma, Lewis Lung; Cell Proliferation; Herbal Medicine; Mice; Mice, Inbred C57BL; Neoplasm Metastasis

Previous work suggested that functional voltage-gated Na(+) channels (VGSCs) are expressed specifically in strongly metastatic cells of rat and human prostate cancer (PCa), thereby raising the possibility that VGSC activity could be involved in cellular behavior(s) related to the metastatic cascade. In the present study, the possible role of VGSCs in the lateral motility of rat PCa cells was investigated in vitro by testing the effect of modulators that either block or enhance VGSC activity. Two rat PCa cell lines of markedly different metastatic ability were used in a comparative approach: the strongly metastatic MAT-LyLu and the weakly metastatic AT-2 cell line, only the former being known to express functional VGSCs. Using both electrophysiological recording and a motility assay, the effects of two VGSC blockers (tetrodotoxin and phenytoin) and four potential openers (veratridine, aconitine, ATX II, and brevetoxin) were monitored on (a) Na(+) channel activity and (b) cell motility over 48 h. Tetrodotoxin (at 1 microM) and phenytoin (at 50 microM) both decreased the motility index of the MAT-LyLu cell line by 47 and 11%, respectively. Veratridine (at 20 microM) and brevetoxin (at 10 nM) had no effect on the motility of either cell line, whilst aconitine (at 100 microM) and ATX II (at 25 pM) significantly increased the motility of the MAT-LyLu cell line by 15 and 9%, respectively. Importantly, at the concentrations used, none of these drugs had effects on the proliferation or viability of either cell line. The results, taken together, would suggest strongly that functional VGSC expression enhances cellular motility of PCa cells. The relevance of these findings to the metastatic process in PCa is discussed.

Topics: Aconitine; Animals; Carcinoma; Cell Division; Cell Movement; Cnidarian Venoms; Cytoskeletal Proteins; Cytoskeleton; Gene Expression Regulation, Neoplastic; Ion Transport; Male; Marine Toxins; Neoplasm Metastasis; Oxocins; Patch-Clamp Techniques; Phenytoin; Prostatic Neoplasms; Rats; Sodium Channel Blockers; Sodium Channels; Tetrodotoxin; Tumor Cells, Cultured; Veratridine