Gene Expression Profiling and Pathway Network Analysis Predicts a Novel Antitumor Function for a Botanical-Derived Drug, PG2

Yu-Lun Kuo; Chun-Houh Chen; Tsung-Hsien Chuang; Wei-Kai Hua; Wey-Jinq Lin; Wei-Hsiang Hsu; Peter Mu-Hsin Chang; Shih-Lan Hsu; Tse-Hung Huang; Cheng-Yan Kao; Chi-Ying F Huang

doi:10.1155/2015/917345

Gene Expression Profiling and Pathway Network Analysis Predicts a Novel Antitumor Function for a Botanical-Derived Drug, PG2

Evid Based Complement Alternat Med. 2015:2015:917345. doi: 10.1155/2015/917345. Epub 2015 Apr 20.

Authors

Affiliations

¹ Department of Computer Science and Information Engineering, National Taiwan University, No. 1, Section 4, Roosevelt Road, Taipei 10617, Taiwan.
² Institute of Statistical Science, Academia Sinica, No. 128, Section 2, Academia Road, Nankang, Taipei 11529, Taiwan.
³ Immunology Research Center, National Health Research Institutes, No. 35, Keyan Road, Zhunan, Miaoli County 35053, Taiwan.
⁴ Institute of Biopharmaceutical Sciences, National Yang-Ming University, No. 155, Section 2, Linong Street, Taipei 11221, Taiwan.
⁵ Institute of Clinical Medicine, National Yang-Ming University, No. 155, Section 2, Linong Street, Taipei 11221, Taiwan ; Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Section 2, Shipai Road, Beitou, Taipei 11217, Taiwan.
⁶ Department of Education and Research, Taichung Veterans General Hospital, No. 1650 Taiwan Boulevard Section 4, Taichung 40705, Taiwan.
⁷ Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, No. 222, Maijin Road, Keelung 20401, Taiwan ; Graduate Institute of Clinical Medicine Sciences, Chang Gung University, No. 259, Wenhua 1st Raod, Taoyuan 33302, Taiwan ; Graduate Institute of Traditional Chinese Medicine, Chang Gung University, No. 259, Wenhua 1st Road, Taoyuan 33302, Taiwan.
⁸ Department of Computer Science and Information Engineering, National Taiwan University, No. 1, Section 4, Roosevelt Road, Taipei 10617, Taiwan ; Graduate Institute of Biomedical Electronic and Bioinformatics, National Taiwan University, No. 1, Section 4, Roosevelt Road, Taipei 10617, Taiwan.
⁹ Institute of Biopharmaceutical Sciences, National Yang-Ming University, No. 155, Section 2, Linong Street, Taipei 11221, Taiwan ; Institute of Clinical Medicine, National Yang-Ming University, No. 155, Section 2, Linong Street, Taipei 11221, Taiwan ; Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, No. 155, Section 2, Linong Street, Taipei 11221, Taiwan.

Abstract

PG2 is a botanical drug that is mostly composed of Astragalus polysaccharides (APS). Its role in hematopoiesis and relieving cancer-related fatigue has recently been clinically investigated in cancer patients. However, systematic analyses of its functions are still limited. The aim of this study was to use microarray-based expression profiling to evaluate the quality and consistency of PG2 from three different product batches and to study biological mechanisms of PG2. An integrative molecular analysis approach has been designed to examine significant PG2-induced signatures in HL-60 leukemia cells. A quantitative analysis of gene expression signatures was conducted for PG2 by hierarchical clustering of correlation coefficients. The results showed that PG2 product batches were consistent and of high quality. These batches were also functionally equivalent to each other with regard to how they modulated the immune and hematopoietic systems. Within the PG2 signature, there were five genes associated with doxorubicin: IL-8, MDM4, BCL2, PRODH2, and BIRC5. Moreover, the combination of PG2 and doxorubicin had a synergistic effect on induced cell death in HL-60 cells. Together with the bioinformatics-based approach, gene expression profiling provided a quantitative measurement for the quality and consistency of herbal medicines and revealed new roles (e.g., immune modulation) for PG2 in cancer treatment.