Abstract A171: Antitumor effects of intervenolin, a novel natural compound with anti-Helicobacter pylori activity, and its synthetic derivatives on gastric and colorectal cancer cells.

Abstract

Abstract Tumor tissues are composed of not only tumor cells but also the surrounding stroma. While the stroma consists of various kinds of cells, among them fibroblasts-like stromal cells can regulate the growth and metastasis of tumor cells positively or negatively. Thus, the modulation of the tumor-stromal cell interactions can be a new antitumor strategy. We have been searching compounds that modulate the interactions using coculture system of tumor cells and stromal cells. In the course of our screening, we have isolated a novel compound, intervenolin, from the culture broth of Nocardia sp. ML96-86F2. Intervenolin inhibits the growth of human gastric and colorectal cancer cell lines when cocultured with the respective organ-derived stromal cells more strongly than that of the cancer cells cultured alone. To improve low yield of intervenolin from the bacterial culture and to create more potent compounds, we have synthesized intervenolin and its derivatives. Some of the derivatives also show the same effect as intervenolin in vitro. Furthermore, intervenolin and its derivatives show antitumor effects against xenograft models of human gastric cancer cells and also MDR-expressing colorectal cancer cells in vivo. Furthermore, intervenolin and its derivatives exert selective anti-Helicobacter pylori activity. We are now investigating the mechanism of its action and trying to synthesize more potent its derivatives. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A171. Citation Format: Manabu Kawada, Hiroyuki Inoue, Shun-ichi Ohba, Hikaru Abe, Masaki Hatano, Masahide Amemiya, Chigusa Hayashi, Ihomi Usami, Takumi Watanabe, Masayuki Igarashi, Tohru Masuda, Masakatsu Shibasaki, Akio Nomoto. Antitumor effects of intervenolin, a novel natural compound with anti-Helicobacter pylori activity, and its synthetic derivatives on gastric and colorectal cancer cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A171.