3,246 research outputs found
MicroRNAs and Chinese Medicinal Herbs: New Possibilities in Cancer Therapy
In recent decades Chinese medicine has been used worldwide as a complementary and alternative medicine to treat cancer. Plenty of studies have shown that microRNAs (miRNAs) play fundamental roles in many pathological processes, including cancer, while the anti-cancer mechanisms of Chinese medicinal herbs targeting miRNAs also have been extensively explored. Our previous studies and those of others on Chinese medicinal herbs and miRNAs in various cancer models have provided a possibility of new cancer therapies, for example, up-regulating the expression of miR-23a may activate the positive regulatory network of p53 and miR-23a involved in the mechanism underlying the anti-tumor effect of berberine in hepatocellular carcinoma (HCC). In this review, we survey the role of Chinese medicinal herbal products in regulating miRNAs in cancer and the use of mediating miRNAs for cancer treatment. In addition, the controversial roles of herb-derived exogenous miRNAs in cancer treatment are also discussed. It is expected that targeting miRNAs would provide a novel therapeutic approach in cancer therapy by improving overall response and survival outcomes in cancer treatment, especially when combined with conventional therapeutics and Chinese medicinal herbal products. © 2015 by the authors; licensee MDPI, Basel, Switzerland.published_or_final_versio
Suppression of Vascular Endothelial Growth Factor via Inactivation of Eukaryotic Elongation Factor 2 by Alkaloids in Coptidis rhizoma in Hepatocellular Carcinoma
Aim of study: To investigate the inhibitory effect of Coptidis rhizome aqueous extract (CRAE) on vascular endothelial growth factor (VEGF) expression and tumor angiogenesis in hepatocellular carcinoma (HCC). Methods: Quality control of CRAE was determined. Secretion of VEGF protein and expression of its mRNA in MHCC97L and Hep G2 cells were measured with enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction. Synthesis of nascent protein was determined by AHA-protein-labeling technologies. The in vivo antiangiogenic effect of CRAE was evaluated with a xenograft model. Results: Absence of organochlorine pesticides in CRAE was found, and phytochemical analysis showed that its components were in proportion of magnoflorine 2.2%, jatrorrhizine 1.68%, palmatine 4.4%, and berberine 13.8%. CRAE exhibited significant inhibition on VEGF secretion from MHCC97L and HepG2 cells at nontoxic doses. The mRNA transcripts of VEGF could not be inhibited by CRAE; however, synthesis of VEGF nascent protein was potently blocked by CRAE. CRAE intervention increased the phosphorylation of eukaryotic elongation factor 2 (eEF2) in HCC cells, which blocked eEF2 activity for proceeding nascent protein synthesis. The activity of eEF2 was restored in CRAE-treated HCC cells in the presence of A484594, leading to the recovery of VEGF expression. Berberine was found to be the major active component in CRAE; however, CRAE is more effective in inhibiting eEF2 activity compared to berberine treatment alone, suggesting the additive effect of other components present. Reduction of tumor size and neovascularization were observed in mice xenograft model. Conclusion: Our study postulates the antiangiogenic effect of CRAE on hepatocellular carcinoma via an eEF2-driven pathway.postprin
A Biomedical Investigation of the Hepatoprotective Effect of Radix salviae miltiorrhizae and Network Pharmacology-Based Prediction of the Active Compounds and Molecular Targets
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Hepatoprotective Effects of Chinese Medicinal Herbs: A Focus on Anti-Inflammatory and Anti-Oxidative Activities
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Autophagy-induced RelB/p52 activation mediates tumour-associated macrophage repolarisation and suppression of hepatocellular carcinoma by natural compound baicalin
Open Access JournalThe plasticity of tumour-associated macrophages (TAMs) has implicated an influential role in hepatocellular carcinoma (HCC). Repolarisation of TAM towards M1 phenotype characterises an immune-competent microenvironment that favours tumour regression. To investigate the role and mechanism of TAM repolarisation in suppression of HCC by a natural compound baicalin, Orthotopic HCC implantation model was used to investigate the effect of baicalin on HCC; liposome-clodronate was introduced to suppress macrophage populations in mice; bone marrow-derived monocytes (BMDMs) were induced to unpolarised, M1-like, M2-like macrophages and TAM using different conditioned medium. We observed that oral administration of baicalin (50 mg/kg) completely blocked orthotopic growth of implanted HCC. Suppression of HCC by baicalin was diminished when mice macrophage was removed by clodronate treatment. Baicalin induced repolarisation of TAM to M1-like phenotype without specific toxicity to either phenotype of macrophages. Baicalin initiated TAM reprogramming to M1-like macrophage, and promoted pro-inflammatory cytokines production. Co-culturing of HCC cells with baicalin-treated TAMs resulted in reduced proliferation and motility in HCC. Baicalin had minimal effect on derivation of macrophage polarisation factors by HCC cells, while directly induced repolarisation of TAM and M2-like macrophage. This effect was associated with elevated autophagy, and transcriptional activation of RelB/p52 pathway. Suppression of autophagy or RelB abolished skewing of baicalin-treated TAM. Autophagic degradation of TRAF2 in baicalin-treated TAM might be responsible for RelB/p52 activation. Our findings unveil the essential role of TAM repolarisation in suppressive effect of baicalin on HCC, which requires autophagy-associated activation of RelB/p52.published_or_final_versio
IRE1α inhibition by natural compound genipin on tumour associated macrophages reduces growth of hepatocellular carcinoma
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Current Status of Herbal Medicines in Chronic Liver Disease Therapy: The Biological Effects, Molecular Targets and Future Prospects
Chronic liver dysfunction or injury is a serious health problem worldwide. Chronic liver disease involves a wide range of liver pathologies that include fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The efficiency of current synthetic agents in treating chronic liver disease is not satisfactory and they have undesirable side effects. Thereby, numerous medicinal herbs and phytochemicals have been investigated as complementary and alternative treatments for chronic liver diseases. Since some herbal products have already been used for the management of liver diseases in some countries or regions, a systematic review on these herbal medicines for chronic liver disease is urgently needed. Herein, we conducted a review describing the potential role, pharmacological studies and molecular mechanisms of several commonly used medicinal herbs and phytochemicals for chronic liver diseases treatment. Their potential toxicity and side effects were also discussed. Several herbal formulae and their biological effects in chronic liver disease treatment as well as the underlying molecular mechanisms are also summarized in this paper. This review article is a comprehensive and systematic analysis of our current knowledge of the conventional medicinal herbs and phytochemicals in treating chronic liver diseases and on the potential pitfalls which need to be addressed in future study. © 2015 by the authors; licensee MDPI, Basel, Switzerland.published_or_final_versio
Red pigment from Saw Palmetto: a natural product for potential alternative cancer treatment
Conference Theme: Anticancer Drug Action and Drug Resistance: from Cancer Biology to the ClinicINTRODUCTION: Saw palmetto is extract of the fruit of Serenoa repens (Bartram) J.K.Small, an edible plant originated from the Southeastern United States. It has been used in traditional, complementary and
alternative medicine as a tonic, expectorant and antiseptic for treatment of various illnesses, especially urinary and reproductive system problems. Approximately 90% of Saw palmetto containing fatty acids and has been claimed for its therapeutic effect on benign prostatic hyperplasia (BPH). Previous studies also suggested the in vitro and in vivo anti-cancer effect of lipidosterolic extract of Saw Palmetto. However, recent epidemiology and randomized trials ...published_or_final_versio
Inhibition of eukaryotic elongation factor-2 confers to tumor suppression by a herbal formulation Huanglian-Jiedu decoction in human hepatocellular carcinoma
ETHNOPHARMACOLOGICAL RELEVANCE:
An oriental medicinal formulation, Huanglian Jiedu Decoction (HLJDD), has been well documented in few Traditional Chinese Medicine Classics 1300 years ago for treatment of heat and dampness-related diseases. Its effect is well accepted in Asian community, including China, Japan and Korea. Recent studies have postulated HLJDD as a regimen for cancer treatment, especially liver cancer, but the underlying mechanism is unknown. The aim of this study was to examine the suppressive effect of HLJDD on the growth of hepatocellular carcinoma (HCC) and its possible underlying mechanism.
METHODS:
Chemical composition of HLJDD was analyzed by high performance liquid chromatography. The tumor suppressive effect of HLJDD was determined on both HCC cells and xenograft model. Nascent protein synthesis was detected with Click-IT protein labeling technology; protein expression was determined by immunoblotting and imunnohistochemical analysis.
RESULTS:
Quality analysis revealed that HLJDD of different batches is consistent in both chemical composition and bioactivities. HLJDD inhibited HCC cell proliferation at its non-toxic doses, and suppressed growth and angiogenesis in xenografted murine model. HLJDD suppressed the synthesis of nascent protein via inactivation of eEF2 without deregulating the translation initiation factors. The major components in HLJDD, geniposide, berberine and baicalin, additively act on eEF2, and contributed to the responsible activity. HLJDD-activated eEF2 kinase (eEF2K) led to eEF2 inactivation, and activation of AMPK signaling may be responsible for the eEF2K induction. Blocked AMPK activity in HLJDD-treated HCC cells attenuated eEF2K activation as well as the inhibitory effect of the formula. In nutrient deprived HCC cells with inactivated eEF2, the inhibitory effect of HLJDD in tumor cell expansion was interfered.
CONCLUSION:
Our results indicate that HLJDD has potential in blocking HCC progression with involvement of eEF2 inhibition.
Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.postprin
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