Preventive Impact Of Alkaloids With Anti-cancer Effect Extracted From Natural Herb And The Derivatives

Background Alkaloids with pharmacological effects are often used as medications and recreational drugs, and are a group, which is one of the major elements of herbal medicine. The theme of this study is to identify novel alkaloid elements with an anti-hTERT effect present in herbs and the derivatives. Methods After narrowing down to 5 herbs that have strong tumor suppressive effects against a hepatocellular carcinoma cell line (HLF) by preliminary sensitivity test using extracts from kampo preparations mainly containing alkaloids, we attempted to identify a common ingredient in them. We performed sensitivity tests on each alkaloid and its derivates using respective optimal concentrations for 2 months, followed by examinations of 7 other lines including SUSM1 cells with alkaloids of interest. We examined ant i -pro l i ferat ive act iv i ty , hTERT mRNA downregulation, topoisomerase activity, apoptosis, cell cycle, and topoisomerase in cancer cells in the same condition used for the sensitivity test. Results These alkaloids have regulated cell proliferation and induced the senescence in cancer cell lines. Dicentrine, one of the alkaloids, remarkably showed anti-cancer effects. The alkaloid with the highest efficacy differed for each cancer cell line, however, dicentrine commonly showed strong anti-cancer ef fects for a l l the cel l l ines. In addi t ion, anti-proliferation activity was not shown in SUSM1 cells immortalized without hTERT expression. Conclusions We found that as an herbal medicine element, alkaloid, with anti-hTERT effect had few adverse effects and the effect of the alkaloids is cancer-specific on the basis of a lack of the anti-proliferative effect on cells without telomerase activity. In traditional Japanese medicine, these elements have been historically administrated as a part of conventional powder, suggesting that they may have a preventive effect on cancer onset. After performing the experiment in vivo, we aim to develop derivatives that can be applied clinically as novel anti-cancer drugs.