Immunomodulatory and anticancer potential of Gan cao (Glycyrrhiza uralensis Fisch.) polysaccharides by CT-26 colon carcinoma cell growth inhibition and cytokine IL-7 upregulation in vitro

Abstract

BackgroundChinese licorice, (Glycyrrhiza uralensis Fisch.) is one of the commonly prescribed herbs in Traditional Chinese Medicine (TCM). Gancao, as commonly known in China, is associated with immune-modulating and anti-tumor potential though the mechanism of action is not well known. In this study, we investigated the in vitro immunomodulatory and antitumor potential of Glycyrrhiza uralensis polysaccharides fractions of high molecular weight (fraction A), low molecular weight (fraction B) and crude extract (fraction C).MethodsCell proliferation and cytotoxicity was investigated using Cell Counting kit 8 (CCK-8) on Intestinal epithelial cell line (IEC-6) and Colon carcinoma cell line (CT-26). IL-7 gene expression relative to GAPDH was analysed using Real time PCR. The stimulation and viability of T lymphocytes was determined by Trypan blue exclusion assay.ResultsG.uralensis polysaccharides did not inhibit proliferation of IEC-6 cells even at high concentration. The ED50 was found to be 100 μg/ml. On the other hand, the polysaccharides inhibited the proliferation of cancer cells (CT-26) at a concentration of ≤50 μg/ml. Within 72 h of treatment with the polysaccharides, expression of IL-7 gene was up-regulated over 2 times. It was also noted that, IEC-6 cells secrete IL-7 cytokine into media when treated with G.uralensis polysaccharides. The secreted IL-7 stimulated proliferation of freshly isolated T lymphocytes within 6 h. The effect of the polysaccharides were found to be molecular weight depended, with low molecular weight having a profound effect compared to high molecular weight and total crude extract.ConclusionOur findings indicate that G.uralensis polysaccharides especially those of low molecular weight have a potential as anticancer agents. Of great importance, is the ability of the polysaccharides to up-regulate anticancer cytokine IL-7, which is important in proliferation and maturation of immune cells and it is associated with better prognosis in cancer. Therefore, immunomodulation is a possible mode of action of the polysaccharides in cancer therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1171-4) contains supplementary material, which is available to authorized users.

Characterization of Microwave-Assisted Extracts of Citrus sinensis Exocarp and Mesocarp Peels for their Pharmaceutical Excipient Potentia

“…91,92 Recent investigations on Glycyrrhiza uralensis have led to the isolation of bioactive compounds like isoprenylated phenols which was found to have therapeutic effects against cancer 96 and liver damage. [97][98][99] Echinatin a potent Nrf2 activator isolated from Glycyrrhiza uralensis attenuated CCl4-induced liver damage in mice indicating its hepatoprotective potential. 99 Free phenols rich ethanol crude extract or ethyl acetate extract activated Nrf2 transcription was measured as significant compared to the aqueous extract rich in flavonoid glycosides and triterpenoids saponins.…”

“…[97][98][99] Echinatin a potent Nrf2 activator isolated from Glycyrrhiza uralensis attenuated CCl4-induced liver damage in mice indicating its hepatoprotective potential. 99 Free phenols rich ethanol crude extract or ethyl acetate extract activated Nrf2 transcription was measured as significant compared to the aqueous extract rich in flavonoid glycosides and triterpenoids saponins. 99 In a study conducted by Joa et al, ethanol extract of G. uralensis licorice root induced apoptosis in MCF-7 human breast cancer cell lines via G1 cell cycle arrest through upregulation of tumour suppressor protein p53, BAX and downregulation of Cyclin E and CdK2 genes.…”

“…99 Free phenols rich ethanol crude extract or ethyl acetate extract activated Nrf2 transcription was measured as significant compared to the aqueous extract rich in flavonoid glycosides and triterpenoids saponins. 99 In a study conducted by Joa et al, ethanol extract of G. uralensis licorice root induced apoptosis in MCF-7 human breast cancer cell lines via G1 cell cycle arrest through upregulation of tumour suppressor protein p53, BAX and downregulation of Cyclin E and CdK2 genes. 97 In another study, Isoliquiritigenin induced apoptosis in MGC-803 gastric cancer cell line was observed.…”

Colorectal Cancer from Molecular Pathways to Gene Therapy

“…al. [58] it was observed that G.uralensis polysaccharides especially those of low molecular weight could be used as anticancer agents. Polysaccharides can up-regulate anticancer cytokine IL-7, which is important in proliferation and maturation of immune cells.…”

Design and Synthesis of New Anticancer Glycyrrhetinic Acids and Oleanolic Acids

“…5) Glycyrrhiza uralensis is a traditional natural product, people have used it as food and medicine to prevent various diseases as early as two thousand years ago. 6) Glycyrrhetinic acid (GA), as one of active component of Glycyrrhiza uralensis, plays a more important role in the pharmacological and shows a variety of pharmacological effects, such as antiviral, 7,8) anti-allergic, 9) anti-inflammatory, 10,11) anti-ulcer 12) and anti-tumor activities. 13,14) Our group has done some research on the synthesis and anticancer activity of glycyrrhetinic acid derivatives, and found that some of them have good anticancer activities.…”