Inhibition of tumor cell growth by adenine is mediated by apoptosis induction and cell cycle S phase arrest

Abstract

Gekko swinhonis has a long standing history in Chinese traditional medicine recognized for its application in treating patients with terminal cancer.In order to discover novel anticancer drugs with high anti-tumor efficacy and low toxicity to normal cells, we aim to investigate the anti-tumor components from Gekko swinhonis.Four nucleosides from the extracted samples were enriched, namely adenosine, guanosine, thymidine and inosine. We evaluated the antitumor effect of the four nucleosides and found that adenosine possessed the strongest anti-tumor effect. Besides, adenine could inhibit the growth of Bel-7402 and Hela cells in a dose and time dependent manner, but not normal human cervical keratinocytes. Bel-7402 and Hela cells had undergone apoptosis 48 hours after treatment as evidenced by morphologic changes under TEM, while adenine blocked cell cycle of tumor cells at S phase and subsequently causing cell cycle exit and promoting apoptosis. Moreover, the pharmacokinetics of adenine was stable in cell culture medium for up to 72 hours. Combining its potency with stability, we conclude adenine makes a promising candidate for an anti-tumor drug.