Sophora flavescens Ait.: Traditional usage, phytochemistry and pharmacology of an important traditional Chinese medicine

M2 macrophages was domesticated by tumor microenvironment to produce some angiogenic molecules and protease, facilitating angiogenesis and matrix breakdown, promoting tumor invasive and metastasis. However, The function of M2 macrophages to progression of eophageal carcinoma, especially Kazakh esophageal carcinoma is still dimness. This study aims to investigate M2 macrophages correlated with matrix metalloproteinase-9 (MMP9) and microvessel density, and the role in the progression of Kazakh esophageal squamous cell carcinoma. CD163 and CD34 as the marker of M2 macrophages and endothelial cells, were used to identify the M2 macrophages density and microvessel density, respectively. Immunohistochemistry staining was evaluated the expression of MMP9. The number of infiltrated CD163-positive M2 macrophages in tumor islets and stroma was significantly higher than in cancer adjacent normal tissues. The increased of M2 macrophages and microvessel density were significantly correlated with more malignant phenotypes including lymph node metastasis and clinical stage progression. Meanwhile, the expression of MMP9 showed much higher level in esophageal squamous cell carcinoma than that in cancer adjacent normal tissues, and high expression of MMP9 in Kazakh esophageal squamous cell carcinoma was significantly associated with age, depth of tumor invasion, lymph node metastasis, and tumor clinical stage. The quantity of M2 macrophages in tumor stroma was positively associated with microvessel density and the expression of MMP9, and as an independent poorly prognostic factor for overall survival time of Kazakh esophageal squamous cell carcinoma. These findings suggest the increased number of M2 macrophages correlated with high expression of MMP9 and high microvessel density may contribute to the tumor aggressiveness and angiogenesis, promoting the progression of Kazakh esophageal squamous cell carcinoma.

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CD163 as a marker of M2 macrophage, contribute to predicte aggressiveness and prognosis of Kazakh esophageal squamous cell carcinoma.

Considered as the second deadliest disease globally, cancer has captured the attention of researchers who have been trying with perseverance to decode its hidden aspects, to find new prognosis methods, and to develop better and more effective treatments. Plants have continuously offered an excess of unique secondary metabolites with remarkable biological applications. Alkaloids, one of the most abundant metabolites, constitute a large conglomerate of basic heterocyclic nitrogen-containing natural compounds which are normally produced by plants as toxic substances. Out of the 27,000 different alkaloids, more than 17,000 have displayed diversified pharmacological properties including anticancer activities. These metabolites have been classified either according to their chemical structures or their taxonomic origin. None of the researched alkaloids have been classified according to their molecular mechanism of action against cancer. In fact, only a fraction of the tremendous number of anticancer alkaloids has been copiously mentioned in journals. Here, we aim to provide a summary of the literature on some of the promising anticancer alkaloids that have not been well discussed previously and to classify them according to their molecular mechanisms of action. This review will provide a better understanding of the anticancer mechanisms of these promising natural products that are a rich reservoir for drug discovery.

https://www.mdpi.com/1420-3049/22/2/250/pdf

Emerging Cytotoxic Alkaloids in the Battle against Cancer: Overview of Molecular Mechanisms.

Oxymatrine (OMT) is a major alkaloid found in radix Sophorae flavescentis extract and has been reported to exhibit various pharmacological activities. We elucidated the detailed molecular mechanism(s) underlying the therapeutic actions of OMT in non-small cell lung cancer (NSCLC) cells and a xenograft mouse model. Because the STAT5 signaling cascade has a significant role in regulating cell proliferation and survival in tumor cells, we hypothesized that OMT may disrupt this signaling cascade to exert its anticancer effects. We found that OMT can inhibit the constitutive activation of STAT5 by suppressing the activation of JAK1/2 and c-Src, nuclear localization, as well as STAT5 binding to DNA in A549 cells and abrogated IL-6-induced STAT5 phosphorylation in H1299 cells. We also report that a sub-optimal concentration of OMT when used in combination with a low dose of paclitaxel produced significant anti-cancer effects by inhibiting cell proliferation and causing substantial apoptosis. In a preclinical lung cancer mouse model, OMT when used in combination with paclitaxel produced a significant reduction in tumor volume. These results suggest that OMT in combination with paclitaxel can cause an attenuation of lung cancer growth both in vitro and in vivo.

https://www.mdpi.com/2072-6694/11/1/49/pdf

Oxymatrine Attenuates Tumor Growth and Deactivates STAT5 Signaling in a Lung Cancer Xenograft Model

Natural compounds are highly effective anticancer chemotherapeutic agents, and the targets of plant-derived anticancer agents have been widely reported. In this review, we focus on the main signaling pathways of apoptosis, proliferation, invasion, and metastasis that are regulated by polyphenols, alkaloids, saponins, and polysaccharides. Alkaloids primarily affect apoptosis-related pathways, while polysaccharides primarily target pathways related to proliferation, invasion, and metastasis. Other compounds, such as flavonoids and saponins, affect all of these aspects. The association between compound structures and signaling pathways may play a critical role in drug discovery.

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Modulation of Multiple Signaling Pathways of the Plant-Derived Natural Products in Cancer.

Oxymatrine is an alkaloid, which is derived from the traditional Chinese herb, Sophora flavescens Aiton. Oxymatrine has been shown to exhibit anti-inflammatory, antiviral, and anticancer properties. The present study aimed to investigate the anticancer effects of oxymatrine in human pros- tate cancer cells, and the underlying molecular mechanisms of these effects. An MTT assay demonstrated that oxymatrine significantly inhibited the proliferation of prostate cancer cells in a time‑ and dose‑dependent manner. In addition, flow cytometry and a terminal deoxynucleotidyl transferase-medi- ated dUTP-biotin nick end-labeling assay suggested that oxymatrine treatment may induce prostate cancer cell apop- tosis in a dose-dependent manner. Furthermore, western blot analysis demonstrated a significant increase in the expression of p53 and bax, and a significant decrease in that of Bcl-2, in prostrate cancer cells in a dose-dependent manner. In vivo analysis demonstrated that oxymatrine inhibited tumor growth following subcutaneous inoculation of prostate cancer cells into nude mice. The results of the present study suggested that the antitumor properties of oxymatrine, may be associ- ated with the inhibition of cell proliferation, and induction of apoptosis, via the regulation of apoptosis-associated gene expression. Therefore, the results may provide a novel approach for the development of prostate cancer therapy using oxymatrine, which is derived from the traditional Chinese herb, Sophora flavescens

https://www.spandidos-publications.com/10.3892/mmr.2015.3338/download

Oxymatrine inhibits the proliferation of prostate cancer cells in vitro and in vivo

Receptors for advanced glycation end products (RAGE) is associated with microvessel density and is a prognostic biomarker for clear cell renal cell carcinoma.

Objective To develop a Simple,accurate,rapid,economic,large-scale detection method for the detection of singe nucleotide polymorphisms (SNPs) metabolic enzymes,using polymerase chain reaction with confronting two-pair primers (PCR-CTPP).Methods The primers of CYP1A1 (A4889G),EPHX1 (A416G) and NQO1 (C609T) were designed for PCR-CTPP,and the PCR conditions were optimized.The results of genotyping were verified by DNA sequencing.The above SNPs were detected by the PCR-CTPP detection method in a randomly selected 183 healthy individuals of Han ethnicity.The genotype frequencies were analyzed and compared with people from other ethnicities.Results The allele-specific bands of CYP1A1 (A4889G),EPHX1 (A416G) and NQO1 (C609T) were successfully amplified by PCR-CTPP under the optimal conditions and the results of genotyping were consistent with DNA sequencing.Among 183 healthy Han individuals,the genotypic distributions of CYP1A1 (A4889G),EPHX1 (A416G) and NQO1 (C609T) showed that the wild-type,homozygous variants,and heterozygotes were 103 (56.3%),8 (4.4%),72 (39.3%) and 142 (77.6%),4 (2.2%),37(20.2% ),60(32.8% ),32 (17.5%),91 (49.7%) respectively.The distributions of genotypes were all in accordance with the Hardy-Weinberg equilibrium (P＞0.05),with statistical differences and with other ethnic populations(P＜0.05).Conclusion The SNPs of metabolic enzymes can be detected by PCR-CTPP method which is simple,accurate,rapid,economic and with large scale.PCR-CTPP can be used for large scale clinical and epidemiological screening.

Key words: 
Polymorphism,singe nucleotide;  Polymerase chain reaction with confronting two-pair primers;  Cytochrome P450;  Epoxide hydrolase;  Quinone oxidoreductase

[Establishment and preliminary application of polymerase chain reaction with confronting two-pair primers for the single nucleotide polymorphisms of metabolic enzymes].

Xiao-Dong Pan

Papers

Oxymatrine inhibits the proliferation of prostate cancer cells in vitro and in vivo

Receptors for advanced glycation end products (RAGE) is associated with microvessel density and is a prognostic biomarker for clear cell renal cell carcinoma.

[Establishment and preliminary application of polymerase chain reaction with confronting two-pair primers for the single nucleotide polymorphisms of metabolic enzymes].