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

Yuan Hui Zhang, Yuan Wang, Ali Hussein Yusufali, Frederick Ashby, Daniel Zhang, Zi Fei Yin, George V. Aslanidi, Arun Srivastava, Chang Quan Ling, Chen Ling

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Conclusion Our studies suggest that the use of TCM cytotoxic genes is a useful therapeutic strategy for treating human cancers in general, and liver tumors in particular.

Objective Little effort has been made to study the protein-encoding genes isolated from traditional Chinese medicine (TCM) drugs, and the delivery of these genes into malignant cells through recombinant adeno-associated virus (rAAV) vectors has not been attempted.

Methods 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 protein expression was confirmed by Western blot assay. Various cancer cell lines were transfected with the above plasmids and cell growth was monitored both in vitro and in vivo. The best cytotoxic gene was further packaged into rAAV vectors, under the control of a liver cancer-specific promoter. The liver tumor growth was then monitored following intratumor administration of the rAAV vectors.

Results The expression plasmids, encoding individual potential cytotoxic genes tagged with FLAG epitope, were successfully generated and sequenced. Among these genes, trichosanthin (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. Furthermore, intratumor injection of rAAV vectors containing the TCS gene significantly inhibited the growth of human hepatocellular carcinoma tumors in a murine xenograft model.

Original languageEnglish (US)
Pages (from-to)483-494
Number of pages12
JournalJournal of Integrative Medicine
Volume12
Issue number6
DOIs
StatePublished - Nov 1 2014
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported in part by theAl esx’ Lemonade Foundation and the Bankhead-Coley Cancer Research Program, 3BN04, Florida Department of Health (to CL); Public Health Service Grants R01 HL-097088 and R21 EB-015684 from the National Institutes of Health, and an institutional grant from the Childrens’Miracle Network (to AS); and the National Natural Science Foundation of China grant No. 81273881 (to CQL).

Publisher Copyright:
© 2014 Journal of Integrative Medicine Editorial Office. E-edition published by Elsevier (Singapore) Pte Ltd. All rights reserved.

Keywords

  • cancer gene therapy
  • cytotoxic genes
  • medicine, Chinese traditional
  • recombinant adeno-associated virus vector
  • trichosanthin

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