Prunella vulgaris Polysaccharide Inhibits Growth and Migration of Breast Carcinoma-Associated Fibroblasts by Suppressing Expression of Basic Fibroblast Growth Factor.

OBJECTIVE: To study the effects of Prunella vulgaris polysaccharide (PVP) on human breast carcinoma-associated fibroblasts (CAFs). METHODS: Cell viability was detected by 3-[4,5-dimethylthiazol-2-yl]-2,5-(3-carboxymethoxyphenyl)-2-4-sulfophenyl)-2H-tetrazolium (MTS) assay. Wound healing experiment and transwell migration assay were used to investigate the anti-migration effects. Flow cytometry was applied to detect cell apoptosis and cell cycle distribution. Reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were used to detect the expression of basic fibroblast growth factor (bFGF) in CAFs. Culture SKBr-3 with CAFs conditioned medium (CAFs-CM) to evaluate the indirect function on the proliferation of breast cancer SKBr-3 cells. RESULTS: PVP inhibited the viability of CAFs by inducing apoptosis (P <0.01) and arresting cell cycle (P <0.01). It also inhibited the migration of CAFs (P <0.01). bFGF promoted CAFs proliferation (P <0.01) and migration (P <0.01), protected CAFs from apoptosis (P <0.05) and reduced G0 phase to 49.06% (P <0.01). However, these effects of bFGF on CAFs could be abrogated by PVP. Culturing SKBr-3 with CAFs-CM, PVP could inhibit the viability of breast cancer SKBr-3 cells indirectly. Moreover, PVP reduced the mRNA expression (P <0.01) and protein secretion of bFGF (P <0.01) in CAFs. CONCLUSION: PVP could exert an anti-cancer effect on breast CAFs by inhibiting bFGF expression, thus inhibiting the growth of breast cancer SKBr-3 cells indirectly.

Cucurbitacin B inhibits the migration and invasion of breast cancer cells by altering the biomechanical properties of cells.

Changes in cellular biomechanical properties affect cell migration and invasion. The natural compound Cucurbitacin B (CuB) has potent anticancer activity; however, the mechanism underlying its inhibitory effect on breast cancer metastasis needs further study. Here, we showed that low-dose CuB inhibited adhesion and altered the viscoelasticity of breast cancer cells, thereby, reducing cell deformability. In vitro and in vivo experiments proved that CuB effectively inhibited the migration and invasion of breast cancer cells. Further studies have found that CuB downregulated the expression of F-actin/vimentin/FAK/vinculin in breast cancer cells, altering the distribution and reorganization of cytoskeletal proteins in the cells. CuB inhibited signaling by the Rho family GTPases RAC1/CDC42/RhoA downstream of integrin. These findings indicate that CuB has been proven to mediate the reorganization and distribution of cytoskeletal proteins of breast cancer cells through RAC1/CDC42/RhoA signaling, which improves the mechanical properties of cell adhesion and deformation and consequently inhibits cell migration and invasion.

Sublingual Nodules: Diagnostic Markers of Metastatic Breast Cancer.

OBJECTIVE: To evaluate the diagnostic significance of sublingual nodules for metastasis of patients with breast cancer and further to explore the mechanisms of sublingual nodules. METHODS: The image data of 117 in-patients with breast cancer in stage I-IV in Tianjin Medical University Cancer Institute and Hospital from December 2009 to September 2011 were assessed retrospectively. All photos of patients' tongue were recorded by the digital camera of uniform type within 1 month after serological examination and regular re-examined by computed tomography (CT), magnetic resonance imaging and positron emission tomography CT. The presence of sublingual nodules was the positive standard. Chi square test and two-independent-sample test were used to determine the diagnostic value between the status of sublingual nodules and Clinico-pathological characteristics. The optimal cut-off of uric acid (UA) level to diagnose sublingual nodules was determined by receiver operating curve (ROC) analysis. RESULTS: Breast cancer patients with sublingual nodules had a higher risk of recurrence and/or metastasis than patients without it (P<0.001). Sublingual nodules was significantly correlated with increased serum UA level (P=0.001). The optimal cut-off value of UA level to diagnose sublingual nodules was 290 µmol/L. Furthermore, the elevated serum UA level (≥290 µmol/L) was significantly related to breast cancer recurrence and/or metastasis (P<0.001). CONCLUSIONS: Sublingual nodules were potential diagnostic markers for metastatic breast cancer. The formation of sublingual nodules was associated with elevated level of serum UA.

Network pharmacology-based and clinically relevant prediction of the active ingredients and potential targets of Chinese herbs in metastatic breast cancer patients.

Chinese Herbal Medicine (CHM) plays a significant role in breast cancer treatment. We conduct the study to ascertain the relative molecular targets of effective Chinese herbs in treating stage IV breast cancer.Survival benefit of CHM was verified by Kaplan-Meier method and Cox regression analysis. A bivariate correlation analysis was used to find and establish the effect of herbs in complex CHM formulas. A network pharmacological approach was adopted to explore the potential mechanisms of CHM.Patients in the CHM group had a median survival time of 55 months, which was longer than the 23 months of patients in the non-CHM group. Cox regression analysis indicated that CHM was an independent protective factor. Correlation analysis showed that 10 herbs were strongly correlated with favorable survival outcomes (P<0.01). Bioinformatics analyses suggested that the 10 herbs might achieve anti-breast cancer activity primarily through inhibiting HSP90, ERα and TOP-II related pathways.

Network pharmacology dissection of multiscale mechanisms of herbal medicines in stage IV gastric adenocarcinoma treatment.

Increasing evidence has shown that Chinese Herbal Medicine (CHM) has efficient therapeutic effects for advanced gastric adenocarcinoma, while the therapeutic mechanisms underlying this treatment remain unclear.In this study, the Kaplan-Meier method and Cox regression analysis were used to evaluate the survival benefit of CHM treatment, and correlation analysis was applied to identify the most effective components in the formulas. A network pharmacological approach was developed to decipher the potential therapeutic mechanisms of CHM.CHM treatment was an independent protective factor. The hazard ratio was 0.364 (95% CI 0.245-0.540; P < 0.001). The median survival time was 18 months for patients who received CHM treatment, while for patients without CHM treatment was decreased to 9 months (P < 0.001). Thirteen out of the total 204 herbs were significantly correlated with favorable survival outcomes (P < 0.05), likely representing the most effective components in these formulas. Bioinformatics analyses suggested that the simultaneous manipulation of multiple targets in proliferation pathways (such as epidermal growth factor receptor, fibroblast growth factor receptor 2, human epidermal growth factor receptor 2, proliferating cell nuclear antigen, and insulin like growth factor 2) and the process of cancer metastasis (collagen families, fibronectin 1 and matrix metalloproteinases families) might largely account for the mechanisms of the 13 herbs against gastric adenocarcinoma.A network pharmacology method was introduced to decipher the underlying mechanisms of CHM, which provides a good foundation for herbal research based on clinical data.

Molecular targets of Chinese herbs: a clinical study of hepatoma based on network pharmacology.

Traditional Chinese medicine (TCM) has been used to treat tumors for years and has been demonstrated to be effective. However, the underlying molecular mechanisms of herbs remain unclear. This study aims to ascertain molecular targets of herbs prolonging survival time of patients with advanced hepatocellular carcinoma (HCC) based on network pharmacology, and to establish a research method for accurate treatment of TCM. The survival benefit of TCM treatment with Chinese herbal medicine (CHM) was proved by Kaplan-Meier method and Cox regression analysis among 288 patients. The correlation between herbs and survival time was performed by bivariate correlation analysis. Network pharmacology method was utilized to construct the active ingredient-target networks of herbs that were responsible for the beneficial effects against HCC. Cox regression analysis showed CHM was an independent favorable prognostic factor. The median survival time was 13 months and the 5-year overall survival rates were 2.61% in the TCM group, while there were 6 months, 0 in the non-TCM group. Correlation analysis demonstrated that 8 herbs closely associated with prognosis. Network pharmacology analysis revealed that the 8 herbs regulated multiple HCC relative genes, among which the genes affected proliferation (KRAS, AKT2, MAPK), metastasis (SRC, MMP), angiogenesis (PTGS2) and apoptosis (CASP3) etc.

Structural characterization and anti-tumor effects of an inulin-type fructan from Atractylodes chinensis.

A fructan (ACPS-1) with a molecular weight of 11.2 kDa was isolated from Atractylodes chinensis rhizome and characterized by chemical derivatization, HPLC, GC-MS, FT-IR, and NMR. Structural analyses revealed that ACPS-1 is predominately composed of fructose and a small amount of glucose and a polymerization degree of about 53. The fructan was deduced to be an inulin-type fructan containing a linear backbone composed of (2→1)-linked ß-d-Fruf residues. The in vitro antitumor activity of ACPS-1 was evaluated on four human cancer cell lines, including a cervical cancer cell line (Hela), two liver hepatocellular carcinoma cell lines (HepG2 and 7721), and an ovarian carcinoma cell line (Skov3). Results showed that ACPS-1 could significantly inhibit Hela, HepG2, and 7721 cell proliferation, especially HepG2, for which the fructan showed a proliferative inhibition rate as high as 87.40%. This result suggests that ACPS-1 may have anticancer potentiality against hepatocellular carcinoma and warrants further investigation.

A Novel Pharmacological Method to Study the Chinese Medicinal Formula Hua-Zheng-Hui-Sheng-Dan.

Objectives. Hua-Zheng-Hui-Sheng-Dan (HZHSD) was used as an experimental model to explore research methods of large formulae in traditional Chinese medicine (TCM) using current molecular biology approaches. Materials and Methods. The trypan blue exclusion assay was used to determine cell viability and cell numbers. Flow cytometry was used to assess cell cycle distribution and apoptosis. The concentration of cyclin D1 was analyzed by enzyme-linked immunosorbent assay. The median effect principle was used in drug combination studies. An orthogonal experimental design was used to estimate the effects of each herb at different concentrations. The HeLa xenograft mouse model was used to compare the antitumor activity of drugs in vivo. Results. Among the 35 herbs that comprise HZHSD, Radix Rehmanniae Preparata (RRP), Caesalpinia sappan (CS), Evodia rutaecarpa (ER), Folium Artemisiae Argyi (FAA), Leonurus japonicus Houtt (LJH), Tumeric (Tu), Radix Paeoniae Alba (RPA), and Trogopterus Dung (TD) effectively inhibited the proliferation of HeLa and SKOV3 cells. Only RRR had an effect on HeLa and SKOV3 cell viability. According to the median effect principle, Angelica sinensis (Oliv.) (AS), Tabanus (Ta), and Pollen Typhae (PT), which were proven to have a significant synergistic inhibitory effect on the proliferation of HeLa cells, were added to the original eight positive herbs. The combination of RPA and AS had a synergistic effect on inducing cell cycle S phase arrest and decreasing intracellular cyclin D1 in HeLa cells. By orthogonal experimental design, LJH and Tu were considered unnecessary herbs. The small formula (SHZHSD) consisted of RPA, AS, RRR, Ta., TD, PT, ER, CS, and FAA and was able to inhibit cell proliferation and induce cell apoptosis. The antitumor effects of HZHSD and SHZHSD were also compared in vivo. Conclusions. Through molecular biology approaches both in vitro and in vivo, research into single drugs, and analysis using the median effect principle and orthogonal experimental design, the small formula (SHZHSD) was determined from the original formula (HZHSD). SHZHSD exhibited superior antitumor activity compared with the original formula both in vitro and in vivo.

Survival Benefits of Western and Traditional Chinese Medicine Treatment for Patients With Pancreatic Cancer.

Traditional Chinese medicine (TCM) is one of the most common complementary and alternative medicines used in the treatment of patients with cancer worldwide. However, the clinical effect of TCM on patients with pancreatic cancer remains unclear. This study was aimed to explore the efficacy of TCM on selected patients with pancreatic cancer and to study the usefulness of multimodality treatment, including TCM and western medicine (WM), in pancreatic cancer.From January 2009 to October 2013, 107 patients with pancreatic cancer were included in this study. Kaplan-Meier curves were used to assess the differences in survival time. Cox regression analysis was performed to determine survival trends adjusted for clinical and demographic factors.Cox regression analysis suggested that elevated CA19-9 levels (P = 0.048), number of cycles of chemotherapy (P = 0.014), and TCM were independent prognostic factors (P < 0.001). The survival hazards ratio of TCM was 0.419 (95% confidence interval [CI], 0.261-0.671). The median overall survival (OS) was 19 months for patients with TCM treatment, while the median OS was 8 months for those without TCM treatment (P < 0.001). Patients who received multimodality treatment using TCM and WM had the best prognosis with a median OS of 19 months (P < 0.001). Patients with heat-clearing, diuresis-promoting and detoxification TCM treatment had a longer survival time (32.4 months) than those with blood-activating and stasis-dissolving (9.8 months) and tonifying qi and yang treatment (6.1 months; P = 0.008).These results indicate that TCM has an important potential value for improving the prognosis of patients with pancreatic cancer, and multimodality treatment, including TCM and WM, leads to the best prognosis. More importantly, we suggest that heat-clearing, diuresis-promoting, and detoxification TCM treatment may improve the efficacy of TCM in pancreatic cancer.

Main Anti-tumor Angiogenesis Agents Isolated From Chinese Herbal Medicines.

With a long history of clinical use, Chinese herbal medicine (CHM) is emerging as a noticeable choice for its multi-level, multi-target and coordinated intervention effects against tumor. Recently, many agents from CHM have shown powerful anti-angiogenic activities against tumor. In this review, we discussed the anti-tumor angiogenic activities of 6 kinds of agents from CHM (sulfated polysaccharides/glycopeptides, flavonoids, artemisinin, arsenic trioxide, ginsenoside, and tanshinone). The underlying pharmacological mechanisms of cancer angiogenesis inhibition by these agents are also gradually shown to us. Sulfated polysaccharides/glycopeptides and flavonoids may have synergistic effects with targeted anti-angiogenic drugs mainly targeting VEGF pathway by inhibiting bFGF and HIF-1α pathway, respectively. It is interesting that artemisinin and arsenic trioxide, two famous natural products worldwide, also have antitumor activity at least in part via angiogenesis inhibition. In addition, some natural products that are widely used for patients with cancer, such as ginseng and danshen, act as double-edged swords for tumor angiogenesis. Our review is aimed at providing an understanding of anti-angiogenic compounds from CHM and we propose that these breakthrough findings may have important implications for targeted-angiogenesis therapy and modernization of CHM.

Chinese medicine herbal treatment based on syndrome differentiation improves the overall survival of patients with unresectable hepatocellular carcinoma.

OBJECTIVE: To investigate the effects of Chinese medicine (CM) herbal treatment based on syndrome differentiation on patients with unresectable hepatocellular carcinoma (HCC). METHODS: A total of 94 patients with unresectable HCC were reviewed between June 2008 and June 2011. Survival analysis was performed between patients who received CM with/without non-curative antitumor treatments of Western medicine (WM) (CM group, 30 cases) and patients who were not treated with CM but with non-curative antitumor treatments of WM or supportive treatment alone (non-CM group, 64 cases). Then, survival analysis was performed between patients treated with CM combined with non-curative antitumor treatments of WM (combination therapy group, 25 cases) and patients with non-curative antitumor treatments of WM alone (non-curative antitumor treatments group of WM, 52 cases). The survival analysis was performed by Kaplan-Meier method and prognostic factors for overall survival (OS) were assessed by the Cox proportional hazards regression model. RESULTS: The median survival time (MST), 1- and 2-year survival rates of the CM group and the non-CM group were 36 months, 76.7%, 56.1% and 12 months, 48.4%, 26.6%, respectively. The Log-rank test revealed significant difference between the two groups in OS (P<0.01). Cox proportional multivariate analysis revealed that CM was an independent favorable prognostic factor for OS. The MST, 1- and 2-year survival rates of combination therapy group and non-curative antitumor treatments group of WM were 36 months, 76.0%, 55.5% and 13 months, 55.8%, 30.8%, respectively. There was significant difference in OS between the two groups (P=0.004). CONCLUSIONS: CM herbs based on syndrome differentiation have positive effects on survival of patients with unresectable HCC. Furthermore, combination therapy of CM and WM are recommended in HCC treatment.

Nodule and eminence on frenulum labii superioris: diagnostic markers for metastatic colorectal cancer.

OBJECTIVE: To determine whether the nodule and eminence on the frenulum labii superioris, location of Yinjiao (DU28) according to the meridian theory, could be used to prognosticate the recurrence of patients with colorectal cancer. METHODS: The data of 101 patients with colorectal cancer in Tianjin Medical University Cancer Institute and Hospital from May 2011 to November 2011 was analyzed. The photos of all patients' frenulum labii superioris were taken. Nodule and eminence on frenulum labii superioris were the positive standard. Biopsy and pathological testing for the nodule were carried out on one patient with large nodule on frenulum labii superioris. RESULTS: Patients with positive frenulum labii superioris had a higher risk of recurrence and/or metastasis than patients with negative frenulum labii superioris. There were no significant differences in diagnosis of recurrence and/or metastasis between the status of frenulum labii superioris and the traditional diagnostic criteria (P =0.238). The Kappa was 0.606 (P <0.001). The sensitivity was 76.0% and the specificity was 85.4%. The pathological report demonstrated that the nodule on frenulum labii superioris was mucosal excrescence with normal structure. CONCLUSION: Nodule and eminence on frenulum labii superioris are potential diagnostic markers for metastatic colorectal cancer.

Recurrence season impacts the survival of epithelial ovarian cancer patients.

BACKGROUND: Several studies indicated that the diagnosis season affects the prognosis of some cancers, such as examples in the prostate, colon and breast This retrospective study aimed to investigate whether the diagnosis and recurrent season impacts the prognosis of epithelial ovarian cancer patients. METHODS: From January 2005 to August 2010, 161 epithelial ovarian cancer patients were analyzed and followed up until August 2013. Kaplan- Meier survival curves and the log-rank test were used to make the survival analysis. Multivariate analysis was conducted to identify independent prognostic factors. RESULTS: The prognostic factors of overall survival in epithelial ovarian cancer patients included age, clinical stage, pathological type, histological grade, residual disease after primary surgery, recurrent season and adjuvant chemotherapy cycles. Moreover, clinical stage, histological grade, residual disease after primary surgery, recurrent season and adjuvant chemotherapy cycles also impacted the progression-free survival of epithelial ovarian cancer patients. The diagnosis season did not have a significantly relationship with the survival of operable epithelial ovarian cancer patients. Median overall survival of patients with recurrent month from April to November was 47 months, which was longer (P < 0.001) than that of patients with recurrence month from December to March (19 months). Median progression-free survival of patients with recurrence month from April to November and December to March was 20 and 8 months, respectively (P < 0.001). CONCLUSION: The recurrence season impacts the survival of epithelial ovarian cancer patients. However, the diagnosed season does not appear to exert a significant influence.

Fucoidan inhibits the growth of hepatocellular carcinoma independent of angiogenesis.

Some sulphated polysaccharides can bind bFGF but are unable to present bFGF to its high-affinity receptors. Fucoidan, a sulphated polysaccharide purified from brown algae, which has been used as an anticancer drug in traditional Chinese medicine for hundreds of years, exhibits a variety of anticancer effects, including the induction of the apoptosis and autophagy of cancer cells, the inhibition of the growth of cancer cells, the induction of angiogenesis, and the improvement of antitumour immunity. Our research shows that fucoidan dose not inhibit the expressions of VEGF, bFGF, IL-8, and heparanase in HCC cells and/or tumour tissues. Moreover, fucoidan exhibited low affinity for bFGF and could not block the binding of bFGF to heparan sulphated. Although fucoidan had no effect on angiogenesis and apoptosis in vivo, this drug significantly inhibited the tumour growth and the expression of PCNA. These results suggest that fucoidan exhibits an anticancer effect in vivo at least partly through inhibition of the proliferation of HCC cells, although it is unable to suppress the angiogenesis induced by HCC.

Gekko-sulfated glycopeptide inhibits tumor angiogenesis by targeting basic fibroblast growth factor.

Basic fibroblast growth factor (bFGF) is a therapeutic target of anti-angiogenesis. Here, we report that a novel sulfated glycopeptide derived from Gekko swinhonis Guenther (GSPP), an anticancer drug in traditional Chinese medicine, inhibits tumor angiogenesis by targeting bFGF. GSPP significantly decreased the production of bFGF in hepatoma cells by suppressing early growth response-1. GSPP inhibited the release of bFGF from extracellular matrix by blocking heparanase enzymatic activity. Moreover, GSPP competitively inhibited bFGF binding to heparin/heparan sulfate via direct binding to bFGF. Importantly, GSPP abrogated the bFGF-stimulated proliferation and migration of endothelial cells, whereas it had no inhibitory effect on endothelial cells in the absence of bFGF. Further study revealed that GSPP prevented bFGF-induced neovascularization and inhibited tumor angiogenesis and tumor growth in a xenograft mouse model. These results demonstrate that GSPP inhibits tumor angiogenesis by blocking bFGF production, release from the extracellular matrix, and binding to its low affinity receptor, heparin/heparan sulfate.

Anticancer effects of 5-fluorouracil combined with warming and relieving cold phlegm formula on human breast cancer.

OBJECTIVE: To investigate the anticancer effects of warming and relieving cold phlegm formula (, WRCP), a Chinese medical mixture composed of the aqueous extracts of Aconitum carmichaeli, Rhizoma bolbostemmatis, Phytolacca acinosa, Panax notoginseng, and Gekko swinhonis Guenther, combined with 5-fluorouracil (5-FU) on human breast cancer in vivo. METHODS: Seventy-two Nu/Nu mice inoculated with MDA-MB-231 breast cancer cells were randomized into the control group, 5-FU group, high-dose WRCP (hWRCP) group, medium-dose WRCP (mWRCP) group, low-dose WRCP (lWRCP) group, or combination of mWRCP and 5-FU group in a 1:1:1:1:1:1 ratio. Drug administration was commenced on the day following tumor implantation. The control group was injected daily with normal saline (N.S.) intraperitoneally; the 5-FU group was injected with 5-FU at 30 mg/kg intraperitoneally every third day for a total of 7 treatments; the hWRCP group, mWRCP group and lWRCP group received daily doses of 5, 1, and 0.2 g/kg of WRCP, respectively, by gastric perfusion; and the combination group was treated with 5-FU plus mWRCP on the same schedules as above. All treatments lasted for 22 days. Tumor volume, tumor weight, inhibition rate of tumor weight, necrosis rate of tumor, organ index, and change in body weight of nude mice were measured. RESULTS: The combination group and the hWRCP group had significantly smaller tumor volumes (580±339 mm(3) and 587±249 mm(3) versus 1055±234 mm(3), respectively), lower tumor weights (0.42±0.29 g and 0.52±0.29 g versus 0.80±0.15 g, respectively), and higher tumor necrosis rates (22.7% and 25.6% versus 9.4%, respectively) as compared with the control group (all <0.05). Similar changes were found in the 5-FU, mWRCP, and lWRCP groups when compared with the control group but were not statistically significant, except for the tumor weight for the 5-FU group. The combination group and the hWRCP group had significantly smaller tumor volumes compared with the 5-FU group (778±202 mm(3), both <0.05). The combination group had the highest tumor inhibition rate (47.7%), followed by the hWRCP group (35.2%) and 5-FU group (28.3%). The 5-FU group had a lower body weight increase (1.37±2.06 g versus 5.60±0.72 g, <0.05) and a lower spleen index (4.064±1.774 mg/10 g versus 5.294±1.796 mg/10 g) as compared with the control group, whereas the combination group reversed the changes in the 5-FU group with the body weight increase of 3.52±1.80 g (P <0.05) and spleen index of 7.036±1.599 mg/10 g (P <0.05). The spleen indices in the hWRCP, mWRCP, and IWRCP group were all significantly higher than that in the 5-FU group (P <0.01 or P<0.05). No significant differences in body weight change were observed in WRCP groups compared with the control group P>0.05). CONCLUSION: The treatment combination of WRCP and 5-FU was more effective in the inhibition of tumor growth than either agent alone and may have potentially additional benefit in improving the general condition and immunity of the mice with human breast cancer cell implants.

Anti-migration effects of Gekko sulfated glycopeptide on human hepatoma SMMC-7721 cells.

Gekko swinhonis Guenther has been used as an anti-cancer drug in traditional Chinese medicine for hundreds of years. Previous studies showed that the Gekko sulfated polysaccharide-protein complex suppressed the proliferation and migration of hepatoma cells. Gekko sulfated glycopeptide α was obtained from Gekko sulfated polysaccharide-protein complex using papain hydrolysis. Gekko sulfated glycopeptide α inhibited the proliferation and migration of SMMC-7721 cells. The secretion of IL-8 and the concentration of intracellular calcium were decreased after Gekko sulfated glycopeptide α exposure. SMMC-7721 cells in the control group showed abnormal features, with a polygonal shape, whereas this changed to a spindle shape after the treatment with Gekko sulfated glycopeptide α. Actin filaments were distributed diffusely along the cell membrane in control cells, whereas those were polymerized and preferentially accumulated in the cytoplasm of treated cells. Microtubules distributed in the cytoplasm of untreated cells were located diffusely whereas those in treated cells were polymerized. Therefore, Gekko sulfated glycopeptide α inhibit the migration of hepatoma cells via reducing the secretion of IL-8 and the concentration of intracellular calcium, as well as regulating the reorganization of cytoskeleton.

Effects of Gekko sulfated polysaccharide-protein complex on human hepatoma SMMC-7721 cells: inhibition of proliferation and migration.

AIM OF THE STUDY: Gekko swinhonis Guenther has been used as an anti-cancer drug in traditional Chinese medicine for hundreds of years. Here we investigated the structural characterization and anti-cancer effects of sulfated polysaccharide-protein complex (GSPP) isolated from Gekko swinhonis Guenther. MATERIALS AND METHODS: The structure of GSPP was characterized by high performance liquid chromatography, gas chromatography, gas chromatography-mass spectrometry, beta-elimination reaction, and NMR spectroscopy. SMMC-7721 cells were used to assess the influence of GSPP on hepatocellular carcinoma. Cell proliferation and survival was determined by trypan blue exclusion assay. Cell migration was performed by wound-healing and transwell assay. The secretion of IL-8 was detected by an enzyme-linked immunosorbent assay kit. Flow cytometry was used to analyze intracellular calcium concentration, as well as cell cycle distribution and apoptosis. Confocal microscopy was used to assess the localization and configuration of actin filaments. RESULTS: GSPP was chemically characterized as a sulfated polysaccharide-protein complex with O-glycopeptide linkages. Our results showed that GSPP inhibited the proliferation of SMMC-7721 cells and blocked cells in the S phase. No direct toxicity against cells was observed. Furthermore, GSPP inhibited the migration of SMMC-7721 cells with the reduction of intracellular calcium. Actin filaments were polymerized and accumulated in the cytoplasm of the treated cells, whereas the secretion of IL-8 was not significantly changed after GSPP exposure. CONCLUSION: We describe an identified sulfated polysaccharide-protein complex, and demonstrate its direct effect on hepatocellular carcinoma cell migration via calcium-mediated regulation of the actin cytoskeleton reorganization.

[Using a new generation of classification system of antineoplastic drugs to guide Chinese medicine research].

A new generation of classification system of antineoplastic drugs was put forward based on comparing the first with the second generation classification system of antineoplastic drugs. Antineoplastic drugs are divided into cytotoxic drug, cells biological behavior regulator, biological response modifier and biochemical modulator. The using of biological response modifier (immune modulator for instance) and biochemical modulator are supplementary methods for Western medicine treatment in tumor, because the cytotoxic effects of Chinese herbs are lower than those of chemotherapeutic drugs. For the new breakthrough of Chinese medicine oncology research, new idea, new technology and new target should be used, the Chinese medicine mechanism should be studied from a new view. Reversing abnormal biological behavior of tumor cells by Chinese medicine could be an important breakthrough of Chinese medicine oncology research.

Induced differentiation of hepatocellular carcinoma by natural products.

Hepatocellular carcinoma is one of the most common malignant tumors worldwide. For the difficulty of the giving sufficient dose because of the poor liver function and the low sensitivity of hepatoma cells for the chemotherapeutic agents, chemotherapy adds little to overall survival of hepatocellular carcinoma patients. The induction of terminal differentiation in tumor cells represents a possible therapeutic strategy with less toxicity. Gekko sulfated polysaccharides, isoverbascoside, Ginsenoside-Rh2, Camptothecin, 9-nitro-camptothecin, tachyplesin, Matrine, tylophorine, 7-OH-4-CH(3)-coumarin and arsenic trioxide are known to have a differentiation-inducing capability on hepatocellular carcinoma in vitro and/or in vivo. Although the therapeutic effect of the differentiation-inducing agents may not be potent when compared with that of conventional chemotherapeutic agents, they have multiple therapeutic targets, low toxicity and less probability of drug resistance. More data are required on the molecular mechanisms of therapeutic effects, dose response and potential toxicities.