Oncotarget. 2017 Apr 28;8(39):65022-65041. doi: 10.18632/oncotarget.17531. eCollection 2017 Sep 12.

Metabolic characterization and pathway analysis of berberine protects against prostate cancer.

Li X1, Zhang A1, Sun H1, Liu Z1, Zhang T1, Qiu S1, Liu L2, Wang X1,2.

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Recent explosion of biological data brings a great challenge for the traditional methods. With increasing scale of large data sets, much advanced tools are required for the depth interpretation problems. As a rapid-developing technology, metabolomics can provide a useful method to discover the pathogenesis of diseases. This study was explored the dynamic changes of metabolic profiling in cells model and Balb/C nude-mouse model of prostate cancer, to clarify the therapeutic mechanism of berberine, as a case study. Here, we report the findings of comprehensive metabolomic investigation of berberine on prostate cancer by high-throughput ultra performance liquid chromatography-mass spectrometry coupled with pattern recognition methods and network pathway analysis. A total of 30 metabolite biomarkers in blood and 14 metabolites in prostate cancer cell were found from large-scale biological data sets (serum and cell metabolome), respectively.

 * We have constructed a comprehensive metabolic characterization network of berberine to protect against prostate cancer. Furthermore, the results showed that berberine could provide satisfactory effects on prostate cancer via regulating the perturbed pathway.

Overall, these findings illustrated the power of the ultra performance liquid chromatography-mass spectrometry with the pattern recognition analysis for large-scale biological data sets may be promising to yield a valuable tool that insight into the drug action mechanisms and drug discovery as well as help guide testable predictions.

Am J Chin Med. 2017;45(7):1497-1511. doi: 10.1142/S0192415X17500811.

Berberine Induces Apoptotic Cell Death via Activation of Caspase-3 and -8 in HL-60 Human Leukemia Cells: Nuclear Localization and Structure-Activity Relationships.

Okubo S1, Uto T1, Goto A1, Tanaka H2, Nishioku T3, Yamada K3, Shoyama Y1.

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Berberine (BBR), an isoquinoline alkaloid, is a well-known bioactive compound contained in medicinal plants used in traditional and folk medicines. In this study, we investigated the subcellular localization and the apoptotic mechanisms of BBR were elucidated. First, we confirmed the incorporation of BBR into the cell visually. BBR showed antiproliferative activity and promptly localized to the nucleus from 5[Formula: see text]min to 15[Formula: see text]min after BBR treatment in HL-60 human promyelocytic leukemia cells. Next, we examined the antiproliferative activity of BBR (1) and its biosynthetically related compounds (2-7) in HL-60 cells. BBR exerted strongest antiproliferative activity among 1-7 and the results of structures and activity relation suggested that a methylenedioxyl group in ring A, an [Formula: see text]-alkyl group at C-9 position, and the frame of isoquinoline may be necessary for antiproliferative activity. Moreover, BBR showed the most potent antiproliferative activity in HL-60 cells among human cancer and normal cell lines tested. Next, we examined the effect of BBR on molecular events known as apoptosis induction. In HL-60 cells, BBR induced chromatin condensation and DNA fragmentation, and triggered the activation of PARP, caspase-3 and caspase-8 without the activation of caspase-9. BBR-induced DNA fragmentation was abolished by pretreatment with inhibitors against caspase-3 and caspase-8, but not against caspase-9. ERK and p38 were promptly phosphorylated after 15 min of BBR treatment, and this was correlated with time of localization to the nucleus of BBR. These results demonstrated that BBR translocated into nucleus immediately after treatments and induced apoptotic cell death by activation of caspase-3 and caspase-8.

Adv Biol Regul. 2017 Oct 3. pii: S2212-4926(17)30166-5. doi: 10.1016/j.jbior.2017.09.012. [Epub ahead of print]

Effects of berberine, curcumin, resveratrol alone and in combination with chemotherapeutic drugs and signal transduction inhibitors on cancer cells-Power of nutraceuticals.

McCubrey JA1, Abrams SL2, Lertpiriyapong K3, Cocco L4, Ratti S4, Martelli AM4, Candido S5, Libra M5, Murata RM6, Rosalen PL7, Lombardi P8, Montalto G9, Cervello M10, Gizak A11, Rakus D11, Steelman LS2.

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Over the past fifty years, society has become aware of the importance of a healthy diet in terms of human fitness and longevity. More recently, the concept of the beneficial effects of certain components of our diet and other compounds, that are consumed often by different cultures in various parts of the world, has become apparent. These "healthy" components of our diet are often referred to as nutraceuticals and they can prevent/suppress: aging, bacterial, fungal and viral infections, diabetes, inflammation, metabolic disorders and cardiovascular diseases and have other health-enhancing effects. Moreover, they are now often being investigated because of their anti-cancer properties/potentials. Understanding the effects of various natural products on cancer cells may enhance their usage as anti-proliferative agents which may be beneficial for many health problems. In this manuscript, we discuss and demonstrate how certain nutraceuticals may enhance other anti-cancer drugs to suppress proliferation of cancer cells.