Abstract C219: Inhibition of cancer cell growth and migration of podophyllotoxin derivative in cancer cells and its mechanistic study.

Abstract

Abstract Although some chemotherapy drugs including tubulin-binding agents had been developed from nature plants, such as podophyllotoxin derivatives, taxanes, and vinca alkaloids, the poor cytotoxic selectivity, serious side-effects and the drug resistances remain the main issues of their therapeutic application. Therefore, we developed a podophyllotoxin derivative named Ching001. Using cell-based studies, we found that Ching001 had cytotoxicity selectivity toward different lung cancer cell lines than to the normal cells. In addition, it prevented lung cancer cell from mitosis by inhibiting the polymerization of microtubule and causing cell cycle arrest at G2/M phase. These events eventually led to apoptosis through activation of the ER-stress signaling. Importantly, Ching001 effectively inhibited the migration ability of lung cancer cell lines through changing microtubule and actin filament dynamics. In the animal tests, 2 mg/kg Ching001 treatment apparently inhibited the tumor growth and the effect was stronger than taxol treatment under same dosage. The hematology and biochemistry tests of blood samples as well as tissue examinations indicated that Ching001 treatment did not show apparent organ toxicities in tested animals. The tumor tissue staining further confirmed that Ching001 induced apoptosis of tumor cells and led to tumor nodule shrinkage. In addition, the result of in vivo experimental metastasis tests showed that 0.2 mg/kg Ching001 treatment decreased the metastasis potential of lung cancer cell. In conclusion, the novel podophyllotoxin derivative, Ching001, could be a potential anti-cancer drug and is valuable to be developed as an anti-metastasis agent as well. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C219.