Tumor-selective cytotoxicity of benzo[c]phenanthridine derivatives from Toddalia asiatica Lam. (original) (raw)
Abstract
Purpose
To develop a novel anti-cancer drug of low side effect against lung adenocarcinoma, the authors screened the bioresources of Okinawa Island, Japan. The medicinal plant Toddalia asiatica Lam_._ contained three benzo[c]phenanthridine derivatives: dihydronitidine (DHN), nitidine (NTD) and demethylnitidine (DMN). Of the three derivatives, DHN had been shown to selectively inhibit the growth of cancer cells in our previous study. Because of similar molecular topology of NTD or DMN to DHN, it can be expected that NTD and DMN also show selective cytotoxicity. The aim of the present study was therefore to examine the selective cytotoxicity of these two compounds in vitro and in vivo.
Methods
Benzo[c]phenanthridine derivatives were isolated from T. asiatica Lam_._, and their chemical structures were identified by interpretation of NMR and MS spectrum. Of the isolated compounds, NTD and DMN were evaluated for cytotoxicity in vitro or in vivo.
Results
NTD as well as DHN selectively reduced the growth of murine and human lung adenocarcinoma in vitro with selective intracellular accumulation. NTD has also been proven to be highly effective in vivo to inhibit the growth of both murine and human lung adenocarcinoma in a subcutaneous xenograft model without any deteriorating side effect. In contrast, DMN had no selective cytotoxicity suggesting that 8-methoxy group of NTD is the critical structural feature for the selective cytotoxicity.
Conclusions
This study thus proves the effectiveness of benzo[c]phenanthridine derivatives as anti-cancer agent in vivo for the first time, and discusses the mechanisms responsible for the selective cytotoxicity.
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Authors and Affiliations
- Center of Molecular Biosciences, University of the Ryukyus, Nishihara, Okinawa, 903-0213, Japan
Hironori Iwasaki, Takafumi Okabe, Masayuki Shimatani & Hirosuke Oku - Department of Bioscience and Biotechnology, Faculty of Agriculture, University of the Ryukyus, Okinawa, 903-0213, Japan
Kensaku Takara - Department of Clinical Laboratory Medicine, School of Medicine, University of the Ryukyus Hospital, Uehara 207, Nishihara, Okinawa, 903-0125, Japan
Takayoshi Toda
Authors
- Hironori Iwasaki
You can also search for this author inPubMed Google Scholar - Takafumi Okabe
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Correspondence toHironori Iwasaki.
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Iwasaki, H., Okabe, T., Takara, K. et al. Tumor-selective cytotoxicity of benzo[c]phenanthridine derivatives from Toddalia asiatica Lam..Cancer Chemother Pharmacol 65, 719–726 (2010). https://doi.org/10.1007/s00280-009-1077-7
- Received: 15 April 2009
- Accepted: 08 July 2009
- Published: 23 July 2009
- Issue Date: March 2010
- DOI: https://doi.org/10.1007/s00280-009-1077-7