Metabolic profiling-based data-mining for an effective chemical combination to induce apoptosis of cancer cells

Green tea extract (GTE) induces apoptosis of cancer cells without adversely affecting normal cells. Several clinical trials reported that GTE was well tolerated and had potential anti-cancer efficacy. Epigallocatechin-3-O-gallate (EGCG) is the primary compound responsible for the anti-cancer effect...

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Bibliographic Details
Published in:Scientific reports 2015-03, Vol.5 (1), p.9474-9474, Article 9474
Main Authors: Kumazoe, Motofumi, Fujimura, Yoshinori, Hidaka, Shiori, Kim, Yoonhee, Murayama, Kanako, Takai, Mika, Huang, Yuhui, Yamashita, Shuya, Murata, Motoki, Miura, Daisuke, Wariishi, Hiroyuki, Maeda-Yamamoto, Mari, Tachibana, Hirofumi
Format: Article
Language:English
Subjects:
AKT protein
Animals
Antineoplastic Agents, Phytogenic - pharmacology
Antioxidants - pharmacology
Apoptosis
Apoptosis - drug effects
Bioactive compounds
Biological activity
Cancer
Cell Line, Tumor
Clinical trials
Computational Biology - methods
Data Mining - methods
Data processing
Disease Models, Animal
Drug Screening Assays, Antitumor
Epigallocatechin-3-gallate
Green tea
Humans
Kinases
Laminin
Liquid chromatography
Mass spectroscopy
Metabolism
Metabolome
Metabolomics - methods
Mice
Multiple myeloma
Multiple Myeloma - drug therapy
Multiple Myeloma - metabolism
Multiple Myeloma - pathology
Neoplasms - metabolism
Nitric oxide
Nitric-oxide synthase
Plant Extracts - pharmacology
Protein kinase C
Rodents
Signal transduction
Signal Transduction - drug effects
Sphingomyelin phosphodiesterase
Tea - chemistry
Tumors
Xenograft Model Antitumor Assays
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Summary:Green tea extract (GTE) induces apoptosis of cancer cells without adversely affecting normal cells. Several clinical trials reported that GTE was well tolerated and had potential anti-cancer efficacy. Epigallocatechin-3-O-gallate (EGCG) is the primary compound responsible for the anti-cancer effect of GTE; however, the effect of EGCG alone is limited. To identify GTE compounds capable of potentiating EGCG bioactivity, we performed metabolic profiling of 43 green tea cultivar panels by liquid chromatography-mass spectrometry (LC-MS). Here, we revealed the polyphenol eriodictyol significantly potentiated apoptosis induction by EGCG in vitro and in a mouse tumour model by amplifying EGCG-induced activation of the 67-kDa laminin receptor (67LR)/protein kinase B/endothelial nitric oxide synthase/protein kinase C delta/acid sphingomyelinase signalling pathway. Our results show that metabolic profiling is an effective chemical-mining approach for identifying botanical drugs with therapeutic potential against multiple myeloma. Metabolic profiling-based data mining could be an efficient strategy for screening additional bioactive compounds and identifying effective chemical combinations.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep09474