Anti‐tumor effects of nitidine on camptothecin‐resistant A549 cells in a xenograft mouse model

Abstract

ABSTRACTAimNitidine (NTD) has been reported to specifically inhibit the growth of human A549 non‐small‐cell lung cancer cells via selective intracellular accumulation. Our recent study showed that NTD preferentially accumulates in camptothecin‐resistant A549 cells (CRC) compared with normal A549 cells (nA549) in vitro. Here, we examined the in vivo anti‐tumor effects of NTD on CRC‐derived tumors and oral treatment on nA549 using a xenograft mouse model.MethodsCancer cells were intradermally inoculated into the back of mice. Then, 100 µg NTD was injected i.p. into the nA549‐ or CRC‐derived tumor‐bearing mice. To confirm the anti‐tumor effects of oral NTD, the nA549‐transplanted mice were fed a diet containing NTD concentrate prepared from Toddalia asiatica Lam.ResultsThe anti‐tumor effect of NTD (i.p.) manifested earlier in CRC‐derived tumors than in the A549‐derived tumors. Oral NTD concentrate also significantly inhibited the growth of the nA549‐derived tumors. NTD was detected in the tumor but not in other tissues in the NTD concentrate‐fed mice.Conclusion CRC‐derived tumor was more susceptible to NTD treatment than nA549‐derived tumor. Furthermore, the anti‐tumor effect of oral NTD and its preferential accumulation in tumor tissues have been demonstrated for the first time. This may be useful for the development of safe anti‐cancer drugs.