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Matrine, one of the main components extracted from a traditional Chinese herb, Sophora flavescens Ait, has displayed anti-cancer activity in several types of cancer cells. This study aims to evaluate the therapeutic benefits of matrine on primary and metastatic breast cancer. Matrine inhibited the viability of and induced apoptosis in human MCF-7 and mouse 4T1 breast cancer cells in a dose-dependent manner in vitro as shown by MTT assay, flow cytometry and laser scanning confocal microscopy. Administration of matrine inhibited the growth of primary tumors and their metastases to lungs and livers, in a dose-dependent manner, in a highly metastatic model of 4T1 breast cancer established in syngeneic Balb/c mice. Tumors from matrine-treated mice had a smaller proliferation index, shown by immunostaining with an anti-Ki-67 antibody, a greater apoptosis index, shown by TUNEL-staining, and a less microvessel density, shown by immunostaining with an anti-CD31 A antibody, compared to the controls. Western blot analysis of tumoral homogenates indicated that matrine therapy reduced the ratio of Bcl-2/Bax, downregulated the expressions of VEGF and VEGFR-2, and increased the activation of caspase-3 and caspase-9. This study suggests matrine may be a potent agent, from a natural resource, for treating metastatic breast cancer because of its anti-apoptotic, anti-proliferative and anti-angiogenic activities.

Corydalis yanhusuo W.T. Wang (YHS) is a traditional Chinese herb widely prescribed for promoting blood circulation, reinforcing vital energy and alleviating pain. Our previous studies showed that an ethanol extract of YHS inhibits metastasis of breast cancer cells in vitro. In the present study, the anti-proliferative effect of the extract was determined by MTT assay and the LDH release was measured with a commercial kit. Intracellular reactive oxygen species (ROS) production and mitochondrial membrane potential (ΔΨm) were monitored by CM- H₂DCF-DA and JC-1 staining, respectively. Cell cycle was analyzed with propidium iodide (PI) staining by flow cytometry and protein expressions were measured by Western blotting. The YHS extract significantly inhibited MCF-7 cell proliferation in a dose-dependent manner. Significant increase of ROS formation and decrease of ΔΨm were observed. Furthermore, it induced MCF-7 cell cycle arrest at the G2/M phases. In addition, the p-cdc-2/cdc-2 protein expression ratio was increased while Rb and p21 protein expressions were decreased.

The YHS extract inhibited MCF-7 proliferation by inducing G2/M cell cycle arrest, which might be mediated by inducing ROS formation, decreasing ΔΨm and regulating cell cycle related protein expressions.

Dehydrocorydaline is an alkaloid isolated from traditional Chinese herb Corydalis yanhusuo W.T. Wang. We discovered that it possessed anti-tumor potential during screening of anti-tumor natural products from Chinese medicine. In this study, its anti-tumor potential was investigated with breast cancer line cells MCF-7 in vitro. The anti-proliferative effect of dehydrocorydaline was determined by MTT assay and the mitochondrial membrane potential (Δ Ψ m) was monitored by JC-1 staining. DNA fragments were visualized by Hoechst 33342 staining and DNA ladder assay. Apoptotic related protein expressions were measured by Western blotting. Dehydrocorydaline significantly inhibited MCF-7 cell proliferation in a dose- dependent manner, which could be reversed by a caspase-8 inhibitor, Z-IETD-FMK. Dehydrocorydaline increased DNA fragments without affecting ΔΨm. Western blotting assay showed that dehydrocorydaline dose-dependently increased Bax protein expression and decreased Bcl-2 protein expression. Furthermore, dehydrocorydaline induced activation of caspase-7,-8 and the cleavage of PARP without affecting caspase-9. These results showed that dehydrocorydaline inhibits MCF-7 cell proliferation by inducing apoptosis mediated by regulating Bax/Bcl-2, activating caspases as well as cleaving PARP.

Ganoderma lucidum (Fr.) Karst is a traditional Chinese herb that has been widely used for centuries to treat various diseases including cancer. Herein, an ethanol-soluble and acidic component (ESAC), which mainly contains triterpenes, was prepared from G. lucidum and its anti-tumor effects in vitro were tested on human breast cancer cells. Our results showed that ESAC reduced the cell viability of MCF-7 and MDA-MB-231 cells in a concentration-dependent manner with IC₅₀ of about 100 μg/mL and 60 μg/mL, respectively. DNA damage was detected by Comet assay and the increased expression of γ-H2AX after ESAC treatment was determined in MCF-7 cells. Moreover, ESAC effectively mediated G1 cell cycle arrest in both concentration- and time-dependent manners and induced apoptosis as determined by Hoechst staining, DNA fragment assay and Western blot analysis in MCF-7 cells. In conclusion, ESAC exerts anti-proliferation effects by inducing DNA damage, G1 cell cycle arrest and apoptosis in human breast cancer cells.

Mesangial cell proliferation is correlated with the progression of renal failure. The purpose of this study was to determine whether a water extract of Poria cocos Wolf (WPC), a well-known medicinal plant, regulates rat mesangial cell proliferation in the presence of high glucose (HG). HG significantly accelerated [³H]-thymidine incorporation, which was inhibited by WPC (1–50 μg/mL) in a dose-dependent manner. Cell migration and fibronectin mRNA expression data also supported the anti-proliferative effect of WPC. Western blot analysis revealed that pretreatment with WPC decreased the expression of cyclins and cyclin-dependent kinases (CDKs) and promoted the expression of p21^waf1/cip1 and p27^kip1. WPC also suppressed HG-induced p38 mitogen-activated protein kinase (p38 MAPK) and extracellular-signal-regulated kinase 1/2 (ERK 1/2) phosphorylation. Furthermore, WPC inhibited HG-induced production of dichlorofluorescein (DCF)-sensitive intracellular reactive oxygen species (ROS). In conclusion, HG promoted mesangial cell proliferation, and WPC inhibited this activity, at least in part, via induction of cell cycle arrest and activation of anti-oxidant properties. Taken together, these results suggest that P. cocos may be a potent regulator of HG-induced proliferation.

Abnormal vascular smooth muscle cell (VSMC) proliferation and migration contribute to the pathogenesis of vascular diseases including atherosclerosis and restenosis. Brazilin isolated from the heartwood of Caesalpinia sappan L. has been reported to exhibit various biological activities, such as anti-platelet aggregation, anti-inflammation, vasorelaxation and pro-apoptosis. However, the functional effects of Brazilin on VSMCs remain unexplored. The present study investigated the potential effects of Brazilin on platelet-derived growth factor (PDGF)-BB induced VSMC proliferation and migration as well as the underlying mechanism of action. VSMC proliferation and migration were measured by Crystal Violet Staining, wound-healing and Boyden chamber assays, respectively. Cell cycle was analyzed by flow cytometry. Enzymatic action of matrix metalloproteinase-9 (MMP-9) was carried out by gelatin zymography. Expression of adhesion molecules, cell cycle regulatory proteins, the phosphorylated levels of PDGF receptor β (PDGF-Rβ), Src, extracellular signal regulated kinase (ERK) and Akt were tested by immunoblotting. The present study demonstrated that pretreatment with Brazilin dose-dependently inhibited PDGF-BB stimulated VSMC proliferation and migration, which were associated with a cell-cycle arrest at G0/G1 phase, a reduction in the adhesion molecule expression and MMP-9 activation in VSMCs. Furthermore, the increase in PDGF-Rβ, Src, ERK1/2 and Akt phosphorylation induced by PDGF-BB were suppressed by Brazilin. These findings indicate that Brazilin inhibits PDGF-BB induced VSMC proliferation and migration, and the inhibitory effects of Brazilin may be associated with the blockade of PDGF-Rβ - ERK1/2 and Akt signaling pathways. In conclusion, the present study implicates that Brazilin may be useful as an anti-proliferative agent for the treatment of vascular diseases.

Humulus scandens, rich in flavonoids, is a traditional Chinese medicine. It is widely used in China to treat tuberculosis, dysentery and chronic colitis. In this study, the major active faction of Humulus scandens (H.S) was prepared. Then, its immunosuppressive effects and underlying mechanisms on T cell activation were investigated in vitro and in vivo. Results showed that H.S significantly inhibited the proliferation of splenocytes induced by concanavalin A, lipopolysaccharides, and mixed-lymphocyte reaction in vitro. Additionally, H.S could dramatically suppress the proliferation and interferon-γ (IFN-γ) production from T cells stimulated by anti-CD3 and anti-CD28. Flow cytometric results confirmed that H.S could suppress the differentiation of IFN-γ-producing type 1 helper T cells (Th1). Furthermore, using ovalbumin immunization-induced T cell reaction and CD4⁺ T-cell-mediated delayed type hypersensitivity reaction, H.S the immunosuppressive effects of H.S was also demonstrated in vivo. Western blot results showed that H.S could impede the activation of both Erk1/2 and P38 in primary T cells triggered by anti-CD3/28. Collectively, the active fraction of H.S showed promising immunosuppressive activities both in vitro and in vivo.

Pulmonary arterial hypertension (PAH) is a serious pulmonary vascular disease. Excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) plays an important role in the course of this disease. Ligustrazine is an alkaloid monomer extracted from the rhizome of the herb Ligusticum chuanxiong. It is often used to treat cardiovascular diseases, but its effect on PAH has rarely been reported. This study aims to explore the protective effect and mechanism of ligustrazine on PAH. In the in vivo experiment, monocrotaline (MCT) was used to induce PAH in rats, and then ligustrazine (40, 80, 160 mg/kg/day) or sildenafil (25 mg/kg/day) was administered. Four weeks later, hemodynamic changes, right ventricular hypertrophy index, lung morphological characteristics, inflammatory factors, phosphoinositide 3-kinase (PI3K), and AKT expression were evaluated. In addition, primary rat PASMCs were extracted by the tissue adhesion method, a proliferation model was established with platelet-derived growth factor-BB (PDGF-BB), and the cells were treated with ligustrazine to investigate its effects on cell proliferation, inflammation, and cell cycle distribution. The results indicate that ligustrazine can markedly alleviate right ventricular systolic pressure, right ventricular hypertrophy, pulmonary vascular remodeling, and inflammation caused by MCT, and that it decreased PI3K and AKT phosphorylation expression. Moreover, ligustrazine can inhibit the proliferation and inflammation of PASMCs and arrest the progression of G0/G1 to S phase through the PI3K/AKT signaling pathway. Therefore, we conclude that ligustrazine may inhibit the proliferation and inflammation of PASMCs by regulating the activation of the PI3K/AKT signaling pathway, thereby attenuating MCT-induced PAH in rats. Collectively, these findings suggest that ligustrazine may be a promising therapeutic for PAH.

Colon cancer, a common type of malignant tumor, seriously endangers human health. However, due to the relatively slow progress in diagnosis and treatment, the clinical therapeutic technology of colon cancer has not been substantially improved in the past three decades. The present study was designed to investigate the effects and involved mechanisms of schisandrin B in cell growth and metastasis of colon cancer. C57BL/6 mice received AOM and dextran sulfate sodium. Mice in treatment groups were gavaged with 3.75–30 mg/kg/day of schisandrin B. Transwell chamber migration, enzyme-linked immunosorbent assay (ELISA), Western blot analysis, immunoprecipitation (IP) and immunofluorescence were conducted, and HCT116 cell line was employed in this study. Data showed that schisandrin B inhibited tumor number and tumor size in the AOD+DSS-induced colon cancer mouse model. Schisandrin B also inhibited cell proliferation and metastasis of colon cancer cells. We observed that schisandrin B induced SMURF2 protein expression and affected SIRT1 in vitro and in vivo. SMURF2 interacted with SIRT1 protein, and there was a negative correlation between SIRT1 and SMURF2 expressions in human colorectal cancer. The regulation of SMURF2 was involved in the anticancer effects of schisandrin B in both in vitro and in vivo models. In conclusion, the present study revealed that schisandrin B suppressed SIRT1 protein expression, and SIRT1 is negatively correlated with the induction of SMURF2, which inhibited cell growth and metastasis of colon cancer. Schisandrin B could be a leading compound, which will contribute to finding novel potential agents and therapeutic targets for colon cancer.

Liver cancer is a gastrointestinal malignant tumor with high lethality. The prognosis of liver cancer remains poor. Compounds derived from natural products have been confirmed to alleviate the progression of various diseases, including cancers. Additionally, 6-Shogaol has been reported to induce apoptosis in liver cancer cells. However, the mechanism by which 6-shogaol regulates apoptosis in liver cancer cells remains unclear. To investigate the function of 6-shogaol in liver cancer, RT–qPCR and western blotting were used to detect the expression of TLR4 and FOXO3a in liver cancer cells, respectively. The OD value of liver cancer cells was measured using the MTT assay. Flow cytometry was used to measure cell apoptosis. 6-Shogaol inhibited the growth of liver cancer cells. TLR4 and Wnt/$\beta$-catenin were upregulated in liver cancer cells, and FOXO3a was inactivated, but 6-Shogaol reversed the expression of TLR4, Wnt/$\beta$-catenin and FOXO3a in liver cancer cells. Additionally, TLR4 overexpression partially reversed the inhibitory effect of 6-shogaol on the progression of liver cancer cells via Wnt/$\beta$-catenin signaling. Furthermore, the 6-shogaol-induced increase in FOXO3a expression in liver cancer was notably suppressed by TLR4 or Wnt/$\beta$-catenin upregulation. Thus, 6-Shogaol suppresses the progression of liver cancer by mediating Wnt/$\beta$-catenin signaling and is a potential agent for the treatment of liver cancer.

The search for natural and efficacious antineoplastic drugs, with minimal toxicity and side effects, is an important part of antitumor drug research and development. Tanshinone IIA is the most evaluated lipophilic active component of Salvia miltiorrhiza. Tanshinone IIA is a path-breaking traditional drug applied in cardiovascular treatment. It has also been found that tanshinone IIA plays an important role in the digestive, respiratory and circulatory systems, as well as in other tumor diseases. Tanshinone IIA significantly inhibits the proliferation of several types of tumors, blocks the cell cycle, induces apoptosis and autophagic death, in addition to inhibiting cell migration and invasion. Among these, the regulation of tumor-cell apoptosis signaling pathways is the key breakthrough point in several modes of antitumor therapy. The PI3K/AKT/MTOR signaling pathway and the JNK pathway are the key pathways for tanshinone IIA to induce tumor cell apoptosis. In addition to glycolysis, reactive oxygen species and signal transduction all play an active role with the participation of tanshinone IIA. Endogenous apoptosis is considered the main mechanism of tumor apoptosis induced by tanshinone IIA. Multiple pathways and targets play a role in the process of endogenous apoptosis. Tanshinone IIA can protect chemotherapy drugs, which is mainly reflected in the protection of the side effects of chemotherapy drugs, such as neurotoxicity and inhibition of the hematopoietic system. Tanshinone IIA also has a certain regulatory effect on tumor angiogenesis, which is mainly manifested in the control of hypoxia. Our findings indicated that tanshinone IIA is an effective treatment agent in the cardiovascular field and plays a significant role in antitumor therapeutics. This paper reviews the pharmacological potential and inhibitory effect of tanshinone IIA on cancer. It is greatly anticipated that tanshinone IIA will be employed as an adjuvant in the treatment of various cancers.

Baicalin was reported to facilitate the apoptosis of colon cells and inhibit tumor growth in vivo. This study aimed to explore the specific mechanism and function of baicalin on colon cells. Relative mRNA levels were tested via qPCR. Cell proliferation, viability, and cell cycle phases were evaluated using MTT, colony formation, and flow cytometry assays, respectively. The interaction between miR-139-3p and cyclin-dependent kinase 16 (CDK16) was measured via a dual-luciferase reporter assay. Immunohistochemistry was used to count the positivity cells in tumor tissues collected from treated xenografted tumor mice. The results showed that baicalin increased miR-139-3p expression while also decreasing CDK16 levels, blocking the cell cycle, and inhibiting cell proliferation in colon cancer cells. miR-139-3p silencing or CDK16 overexpression abolished the inhibitory effects of baicalin on colon cancer proliferation. miR-139-3p directly targeted and interacted with CDK16 at the cellular level. The protective functions of miR-139-3p knockdown on tumor cells were abrogated by silencing CDK16. The combination of baicalin treatment and CDK16 knockdown further inhibited tumor growth of xenografted tumor mice compared with the groups injected with only sh-CDK16 or baicalin in vivo. In conclusion, baicalin inhibited colon cancer growth by modulating the miR-139-3p/CDK16 axis.

Breast cancer is one of the most common malignancies in women, and exhibits high metastasis, recurrence and fatality rates. Novel therapies for breast cancer are constantly emerging, such as targeted therapy, oncolytic virotherapy, and immunotherapy. Despite their potential, these new therapies are still in their infancy, and chemotherapy remains the standard treatment for breast cancer. Therefore, it is of great significance to develop safe and efficient treatment drugs or adjuvants for breast cancer treatment. Traditional Chinese medicine (TCM) has a long clinical history in China, in which Scutellaria baicalensis Georgi exhibits favorable antibreast cancer activities. We therefore conducted a systematic review of the available literature to better understand the molecular mechanisms of S. baicalensis in breast cancer treatment. S. baicalensis and its active components (baicalein, baicalin, wogonin, wogonoside, oroxylin A and scutellarin) exhibited promising antibreast cancer activity through proliferation inhibition, apoptosis induction, invasion and metastasis blockading, and drug-resistance and non-coding RNA regulation. Additionally, senescence, autophagy, angiogenesis, and glycolysis mechanisms were observed to play a role in their antibreast cancer activity. Furthermore, multiple signaling pathways contributed to the antitumor effects of S. baicalensi, such as the NF-$\kappa$B, Wnt/$\beta$-catenin, SATB1, Bcl2 family proteins, Caspase, PI3K/Akt, mTOR, ERK, p38-MAPK, TGF-$\beta$/Smad, and Hippo/YAP pathways. This review provides valuable insights into the role of S. baicalensis as a breast cancer treatment and acts as a foundation for further investigations in this field.

This paper deals with the interaction between dispersed cancer cells and the major populations of the immune system, namely, the T helper cells, T Cytotoxic cells, B cells, and antibodies produced. The system is described by a set of five ordinary differential equations. Both local and global stability of the system has been investigated. It has been observed that under appropriate conditions this interaction is capable of controlling the growth of these cancer cells. The analytical findings are supported by numerical and computational analytical methods.

The goal of this paper is to solve mathematical model equations on solid tumour growth and compute their parameter values by applying growth rates of prostate cancer cell lines in vivo. For these computations, we investigate previously developed C3(1)/Tag transgenic models of prostate cancer. To make the computations fast, we have constructed an algorithm, which is based on small amounts of spatial grid-points and obtained a correspondence between the in vivo growth of tumours and the solutions of the model equations.

Growth factors have been shown to play a critical role in enhancing tissue healing. In this study, we evaluate the effect of growth factors on cell proliferation and matrix synthesis. Fibroblasts were derived from medial collateral ligaments (MCLs) of goats and grown in culture. Basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF-BB), epidermal growth factor (EGF), and transforming growth factor (TGF-β₁) were used for the treatment of cells. It was found that bFGF, PDGF-BB and EGF significantly increased proliferation of the goat MCL fibroblasts. In addition, among these three growth factors, bFGF, at the concentration of 1.0 ng/ml, had the maximal effect on cell proliferation. Furthermore, both TGF-β₁ and EGF significantly increased collagen and noncollagenous protein syntheses of goat MCL fibroblasts. The results of this study may be used as baseline data for the application of growth factors to enhance MCL healing in a goat model.

Long-term use of thiazolidinedione (TZD) antidiabetic agents in patients with type 2 diabetes mellitus has been shown to increase the incidence of osteoporosis. Mechanical loading can enhance bone mass by promoting bone formation and suppressing bone resorption, which may be beneficial to patients with TZD-induced osteoporosis. In this study, we examined the cooperative effect of fluid shear stress (FSS) and ciglitazone (CIG), a type of TZD, on osteoblasts. The proliferation, osteoblast differentiation-related mRNA expression and translocation of nuclear factor κB (NFκB) of osteoblasts were assessed. The results show that CIG significantly decreased the proliferation of osteoblasts, inhibited the translocation of NFκB to the nucleus and reduced the mRNA expression of COX-2, IGF, Runx2 and OCN. At the same time, CIG also increased the mRNA expression of PPARγ. Conversely, FSS significantly increased the proliferation of osteoblasts, promoted the translocation of NFκB to the nucleus and increased the mRNA expression of COX-2, IGF, Runx2 and OCN but decreased the mRNA expression of PPARγ. When FSS and CIG were combined, FSS counteracted the effects of CIG on osteoblasts. Taken together, the current results suggest that FSS is able to arrest the effects of CIG on the proliferation and differentiation of osteoblasts.

Oxygen concentration plays a key role in cell survival and viability. Besides, it has important effects on essential cellular biological processes such as cell migration, differentiation, proliferation and apoptosis. Therefore, the prediction of the cellular response to the alterations of the oxygen concentration can help significantly in the advances of cell culture research. Here, we present a 3D computational mechanotactic model to simulate all the previously mentioned cell processes under different oxygen concentrations. With this model, three cases have been studied. Starting with mesenchymal stem cells within an extracellular matrix with mechanical properties suitable for its differentiation into osteoblasts, and under different oxygen conditions to evaluate their behavior under normoxia, hypoxia and anoxia. The obtained results, which are consistent with the experimental observations, indicate that cells tend to migrate toward zones with higher oxygen concentration where they accelerate their differentiation and proliferation. This technique can be employed to control cell migration toward fracture zones to accelerate the healing process. Besides, as expected, to avoid cell apoptosis under conditions of anoxia and to avoid the inhibition of the differentiation and proliferation processes under conditions of hypoxia, the state of normoxia should be maintained throughout the entire cell-culture process.

Spinal cord injury (SCI) is a severe neurological disease. Although surgery within 8h after SCI can substantially reduce paraplegia, most patients still suffer from hypomusculariasis after neuron recovery, which results in insufficient lower limb muscles to support bodyweight. Currently, there is no effective method to prevent muscle atrophy. Previous studies have shown that low-frequency electromagnetics (LFE) can stimulate the differentiation, proliferation and fusion of muscle satellite cells, however, the optimal electromagnetic strength and effects on the immune system have not been established. Here, we investigated the influence of LFE at different electromagnetic strengths on muscle cell recovery and assessed the impact of chronic LFE on the immune system of SCI rats. The rat immune system was rapidly activated after SCI. High-energy LFE provoked intensive immune responses, while low-energy LFE did not affect immune responses. Simultaneously, LFE effectively prevented myotube reduction and atrophy in SCI rats. The mRNA and protein levels of Pax7 and MyoD were increased after LFE at both high and low electromagnetic strengths, with the latter leading to more robust increases. Indeed, LFE remarkably induced muscle cell fusion. Together, our results demonstrated that LFE activates muscle satellite cells via stimulating myogenic factors. Chronic low-energy LFE is a safe therapy with no adverse impact on the immune system of SCI rats. LFE with 1.5 mT energy should be considered as an optimal therapeutic strategy.

Platelet-rich fibrin (PRF) has been widely used to accelerate wound and bone healing in human patients. The aim of the study was to establish a canine bone marrow-derived stromal cell (BMSC) culture system and to investigate the effect of PRF on these cells. PRF was prepared using density gradient centrifugation and BMSCs were obtained from the fracture sites of 23 dogs during surgical procedures and individually analyzed. Canine BMSCs were either cultured in osteogenic medium or cultured with/without the presence of PRF. Canine BMSCs expressed similar surface antibodies to mesenchymal stem cells and were able to undergo osteogenic differentiation in osteogenic medium. PRF stimulated proliferation of BMSCs, but PRF alone had no effect on osteogenic differentiation. This study provides useful information about the proliferation effect of PRF, and the canine culture system in the presence of osteogenic medium allows the differentiation of BMSCs in vitro. These results may benefit future application in the clinic.