Screening Active Compounds from Garcinia Species Native to China Reveals Novel Compounds Targeting the STAT/JAK Signaling Pathway.

Linfeng Xu,Wenwei Fu,Yanhui Zhao,Yuanzhi Lao,Yingjia Zhang,Jian Qin,Hongxi Xu

doi:10.1155/2015/910453

Linfeng Xu, Wenwei Fu + Show 5 more

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https://doi.org/10.1155/2015/910453

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Abstract

Natural compounds from medicinal plants are important resources for drug development. In a panel of human tumor cells, we screened a library of the natural products from Garcinia species which have anticancer potential to identify new potential therapeutic leads and discovered that caged xanthones were highly effective at suppressing multiple cancer cell lines. Their anticancer activities mainly depended on apoptosis pathways. For compounds in sensitive cancer line, their mechanisms of mode of action were evaluated. 33-Hydroxyepigambogic acid and 35-hydroxyepigambogic acid exhibited about 1 μM IC50 values against JAK2/JAK3 kinases and less than 1 μM IC50 values against NCI-H1650 cell which autocrined IL-6. Thus these two compounds provided a new antitumor molecular scaffold. Our report describes 33-hydroxyepigambogic acid and 35-hydroxyepigambogic acid that inhibited NCI-H1650 cell growth by suppressing constitutive STAT3 activation via direct inhibition of JAK kinase activity.

Highlights

Compounds from natural herbs are important sources of drugs against a wide variety of diseases, including cancer [1]
We focused on applying different screening platforms to search for novel anticancer compounds from Garcinia plants
We profiled all of the natural compounds that we isolated from Garcinia plants and placed in our compound library using cell viability-based screening

Summary

Introduction

Compounds from natural herbs are important sources of drugs against a wide variety of diseases, including cancer [1]. For the last several decades, natural products have played a very important role as chemotherapeutic agents, either in their natural forms or in synthetically modified forms [2]. Many agents with plant origins (paclitaxel, vinblastine, vincristine, camptothecin, and others) have already been applied as anticancer therapies. Traditional Chinese medicine (TCM) provides an enormous variety of medicinal plants based on thousands of years of experience. With the understanding of the molecular mechanisms of cancer therapies and carcinogenesis, the development of chemotherapeutic agents from natural products is currently being accelerated by collaborations between medicinal chemists and biologists [4, 5]

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