Abstract 5339: Cytotoxic genes from traditional Chinese medicine inhibit tumor growth both in vitro and in vivo

Abstract Traditional Chinese medicine (TCM) has held, and still holds, an important position in primary health care in China, especially in the rural areas. However, scientific evidence of its mechanism is, for the most part, limited and additional better-designed laboratory research is needed. To date, numerous leading chemical compounds from TCM drugs have been identified and evaluated for their anti-tumor effects. However, little effort has been made on the protein-encoding genes isolated from TCM drugs, and the delivery of these genes into malignant cells through recombinant adeno-associated viral (rAAV) vectors has not been attempted. For example, Trichosanthin (TCS), an antiviral plant defense protein found in the root tuber of a TCM herb, Trichosanthes kirilowii, has been used in anti-HIV clinical trials in the USA. Its enzymatic activities were recognized as type I ribosome-inactivating protein. Although the nucleotide sequence of the TCS gene was determined more than 20 years ago, to date, there was little report to deliver TCS-encoding gene into malignant cells. In the present studies, we synthesized the cDNAs of five known cytotoxic proteins isolated from TCM drugs and the FLAG epitope-tagged cDNAs were subcloned into a rAAV plasmid vector. The expression of mRNA was confirmed by RT-PCR and protein expression by Western blot assays against the FLAG tag, respectively. Among these genes, TCS gene yielded the most promising results for the inhibition of cancer cell growth in vitro. The over-expressed TCS functioned as a type I ribosome inactivating protein, followed by inducing apoptosis that is associated with the Bcl-PARP signaling pathway. Next, rAAV vectors containing the TCS gene driven by a liver cancer specific promoter, α-fetoprotein promoter (AFPp) were generated and tested. The results indicated that rAAV-AFPp-TCS vectors significantly inhibited the growth of hHCC cell lines in vitro as well as hHCC tumor growth in vivo following intra-tumor injections in a murine xenograft model. These studies suggest that the use of TCM cytotoxic genes may prove to be a useful therapeutic strategy for treating human cancers in general, and liver tumors in particular. Note: This abstract was not presented at the meeting. Citation Format: Yuanhui Zhang, Yuan Wang, Lina Wang, George Aslanidi, Arun Srivastava, Changquan Ling, Chen Ling. Cytotoxic genes from traditional Chinese medicine inhibit tumor growth both in vitro and in vivo. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5339. doi:10.1158/1538-7445.AM2015-5339