Functional Mechanism of Resveratrol in Inhabiting Growth of Cells ls174t and Its Mechanism in Subcutaneously Transplanted Tumor of Nude Mice

To explore the functional mechanism of Resveratrol against colon cancer cells Is174t and the growth of colon cancer tissue of tumor-bearing mice,MTT method was used to observe the functions of resveratrol for inhibition against cells ls174t in vitro.Transmission electron microscope was used to observe the cell apoptosis.FCM assay was performed to measure the change of the cell apoptosis rate and of cell cycle,RT-PCR method was used to detect the expressions of bc1-2 and bax mRNA.Western blot method was used to detect the expressions of bc1-2 and bax protein.Cells isi74t were transplanted subcutaneously to nude mice to observe the effect of resveratrol on the growth of subcutaneously transplanted tumor.RT-PCR method was used to detect the expressions of bc1-2 and bax mRNA in the tumor tissue.Western blot method was used to detect the expressions of bc1-2 and bax protein in the tumor tissue.Resveratrol has an effect of inhibiting proliferation of cells ls174t in vitro(P<0.01).It is able to induce the apoptosis of cells Is174t,causing the decrease in the expression of bc1-2 and the increase in the expression of bax.Resveratrol could inhibit the growth of subcutaneously transplanted tumor of nude mice(P<0.05),causing the decrease in the expression of bc1-2 and the increase in the expression of bax.Resveratrol can inhibit the growth of cells 174t and the growth of subcutaneously transplanted tumor.The mechanism is possibly related to the induction of the cell apoptosis and the regulation of bc1-2/bax expression.     

Tetraarsenic Tetrasulfide Induced Colon Cancer ls174t Cells Apoptosis

To explore the functional mechanism of tetraarsenic tetrasulfide(As4S4)against the growth and proliferation of colon cancer cells ls174t,MTT method was used to observe the functions of tetraarsenic tetrasulfide for the inhibition of cells ls174t in vitro.Transmission electron microscope was used to observe cell morphologies.FCM assay was performed to measure the change of cell cycle.RT-PCR method was used to detect the expressions of bcl-2 and bax mRNA.Westernblot method was used to detect the expressions of bcl-2 and bax protein.Tetraarsenic tetrasulfide showed an inhibiting effect on the proliferation of cells ls174t in vitro(P＜0.01).It induces the apoptosis of cells ls174t,which is related to the decrease in the expression of bcl-2 and the increase in the expression of bax.     

Resveratrol in management of bone and spinal cancers

Bone cancer is a malignant primary tumour of the bone with different typing, such as, osteosarcoma, chondrosarcoma, Ewing’s sarcoma and fibrosarcoma. Despite the clinical efficacy of conventional therapies of bone cancer, most patients eventually relapse and the disease remains incurable. Therefore, new therapeutic strategies are needed to improve patient outcome. In this review article, we have discussed the role of resveratrol in preventing bone and spinal cancers and therapeutics. Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a natural polyphenol, which has been widely reported as an anticancer molecule. Resveratrol exhibits multiple tumour-suppressing activities in bone cancer by affecting a series of critical events. It has the protective effects against oxidative injury, possesses antiproliferative activity and induces apoptosis in cancer cells. Resveratrol might be a good option for the treatment of different types of bone and spinal cancers.     

Cellular Adhesion Tripeptide RGD Inhibits Growth of Human Ileocecal Adenocarcinoma Cells HCT-8 and Induces Apoptosis

The tripeptide,Arg-Gly-Asp(RGD)motif is an integrin-recognition site found in adhesive proteins present in extracellular matrices(ECM)and in the blood.HCT-8 cells were treated with cellular adhesion tripeptide RGD at various concentrations.MTT assay was performed to examine the growth and proliferation of HCT-8 cells after treatment with RGD for 48 h.Haematoxylin and Eosin(HE)staining and electromicroscope were used to observe the morphology of apoptotic cells.Survivin and flow cytometry were also used to analyze the HCT-8 apoptosis.Cellular adhesion tripeptide RGD significantly inhibits the growth and proliferation of HCT-8 cells in a dose-dependent manner and induces apoptosis of HCT-8.These results indicate that cellular adhesion tripeptide RGD inhibits the growth and proli-feration of tumor HCT-8 cell,probably by the aid of inducing apoptosis of HCT-8 cell.     

Preparation of Catechin Nanoemulsion from Oolong Tea Leaf Waste and Its Inhibition of Prostate Cancer Cells DU-145 and Tumors in Mice

Anti-cancer activity of catechin nanoemulsions prepared from Oolong tea leaf waste was studied on prostate cancer cells DU-145 and DU-145-induced tumors in mice. Catechin nanoemulsions composed of lecithin, Tween-80 and water in an appropriate proportion was prepared with high stability, particle size of 11.3 nm, zeta potential of −67.2 mV and encapsulation efficiency of 83.4%. Catechin nanoemulsions were more effective than extracts in inhibiting DU-145 cell growth, with the IC₅₀ being 13.52 and 214.6 μg/mL, respectively, after 48 h incubation. Furthermore, both catechin nanoemulsions and extracts could raise caspase-8, caspase-9 and caspase-3 activities for DU-145 cell apoptosis, arresting the cell cycle at S and G2/M phases. Compared to control, catechin nanoemulsion at 20 μg/mL and paclitaxel at 10 μg/mL were the most effective in reducing tumor volume by 41.3% and 52.5% and tumor weight by 77.5% and 90.6% in mice, respectively, through a decrease in EGF and VEGF levels in serum.     

In Vivo Anticancer Evaluation of 6b,a Non-Covalent Imidazo[1,2-a]quinoxaline-Based Epidermal Growth Factor Receptor Inhibitor against Human Xenograft Tumor in Nude Mice

Tyrosine kinase inhibitors are validated therapeutic agents against EGFR-mutated non-small cell lung cancer (NSCLC). However, the associated critical side effects of these agents are inevitable, demanding more specific and efficient targeting agents. Recently, we have developed and reported a non-covalent imidazo[1,2-a]quinoxaline-based EGFR inhibitor (6b), which showed promising inhibitory activity against the gefitinib-resistant H1975(L858R/T790M) lung cancer cell line. In the present study, we further explored the 6b compound in vivo by employing the A549-induced xenograft model in nude mice. The results indicate that the administration of the 6b compound significantly abolished the growth of the tumor in the A549 xenograft nude mice. Whereas the control mice bearing tumors displayed a declining trend in the survival curve, treatment with the 6b compound improved the survival profile of mice. Moreover, the histological examination showed the cancer cell cytotoxicity of the 6b compound was characterized by cytoplasmic destruction observed in the stained section of the tumor tissues of treated mice. The immunoblotting and qPCR results further signified that 6b inhibited EGFR in tissue samples and consequently altered the downstream pathways mediated by EGFR, leading to a reduction in cancer growth. Therefore, the in vivo findings were in corroboration with the in vitro results, suggesting that 6b possessed potential anticancer activity against EGFR-dependent lung cancer. 6b also exhibited good stability in human and mouse liver microsomes.     

99mTcN-MIBI在体外肿瘤细胞内的摄取及其与99mTc-MIBI的比较研究

研究了结肠癌细胞CL-187、肺腺癌细胞L-973以及乳腺癌细胞MCF-7分别对^99mTcN-MIBI和^99mTc-MIBI配合物的摄取情况.结果表明,^99mTcN-MIBI在3种肿瘤细胞内培养20～40min时的摄取达到极大值,并且摄取量明显高于^99mTc-MIBI,特别是在结肠癌细胞CL-187中.^99mTcN-MIBI在乳腺癌细胞MCF-7内的摄取量最高,培养40min时的单位细胞摄取百分率约为30%/105个细胞;在结肠癌细胞CL-187内的摄取量次之;在肺腺癌细胞L-973内的摄取量最低.细胞摄取条件实验结果表明:细胞浓度和培养温度的变化均会对细胞摄取产生影响.     

Hispolon Induces Apoptosis,Suppresses Migration and Invasion of Glioblastoma Cells and Inhibits GBM Xenograft Tumor Growth In Vivo

Hispolon, a polyphenol compound isolated from Phellinus linteus, has been reported to exhibit antioxidant, antiproliferative, and antitumor activities. This study aimed to explore the antitumor effects of hispolon on glioblastoma multiforme (GBM) cells in vitro and in vivo. The results revealed that hispolon significantly inhibited GBM cell proliferation and induced apoptosis through caspase-9 and caspase-3 activation and PARP cleavage. Hispolon also induced cell cycle G2/M phase arrest in GBM cells, as supported by flow cytometry analysis and confirmed by a decrease in cyclin B1, cdc2, and cdc25c protein expressions in a dose- and time-dependent manner. Furthermore, hispolon suppressed the migration and invasion of GBM cells by modulating epithelial–mesenchymal transition (EMT) markers via wound healing, transwell assays, and real-time PCR. Moreover, hispolon significantly reduced tumor growth in DBTRG xenograft mice and activated caspase-3 in hispolon-treated tumors. Thus, our findings revealed that hispolon is a potential candidate for the treatment of GBM.     

透明质酸-量子点的制备及应用

基于量子点(QD)独特的光学成像特性, 采用化学合成法制备了透明质酸(HA)修饰的水溶性纳米量子点(HA-QD), 并将其应用于特异性受体CD44的识别研究中. 体外细胞实验结果证实, 在透明质酸受体的介导下, 该纳米复合物可使小鼠肺腺癌细胞LA795显示特异性的荧光成像. 本研究为建立针对透明质酸受体的肿瘤活体检测及研究肿瘤的发生发展提供了重要的纳米靶向荧光探针.     

细胞图案化技术及其在胚胎干细胞研究中的应用

图案化技术的不断创新及在细胞领域研究中的应用使细胞图案化技术成为研究和控制细胞行为的有效实验工具.该技术结合微纳米制备、电化学、表面化学和光化学等手段与方法塑造和细胞相关的物理化学参量,如形貌、粗糙度、亲疏水性等,动态地控制细胞的粘附、脱附、迁移、分化及细胞间相互作用,为细胞生物学研究提供一个崭新的技术平台.本文从细胞...     

Proapoptotic Effect and Molecular Docking Analysis of Curcumin–Resveratrol Hybrids in Colorectal Cancer Chemoprevention

Different hybrids based on curcumin and resveratrol were previously synthesized and characterized by spectroscopic techniques. The most active molecules (3a, 3e, 3i, and 3k) were evaluated in vitro as an approach to determine the possible mechanism of action of the hybrids. The results indicated that the evaluated curcumin/resveratrol hybrids induce mitochondrial instability in SW620 and SW480 cells. Moreover, these molecules caused a loss in membrane integrity, suggesting an apoptotic process mediated by caspases after the treatment with compounds 3i (SW480) and 3k (SW620). In addition, the results suggest that the mechanism of action of the hybrids could be independent of the p53 status. Furthermore, hybrids 3e and 3i caused G0/G1 phase arrest, which highlights the potential of these molecules not only as cytotoxic but also as cytostatic compounds. Hybrids 3e and 3i caused a negative modulation of the matrix metalloproteinase 7 (MMP7) on SW480 cells. These curcumin resveratrol hybrids could be potential candidates for further investigations in the search for potential chemopreventive agents, even in those cases with resistance to conventional chemotherapy because of the lack of p53 expression or function. Molecular docking simulations showed that compounds 3e, 3i, and 3k bind efficiently to proapoptotic human caspases 3/7 proteins, as well as human MMP-7 and p53, which, in turn, could explain at the molecular level the in vitro cytotoxic effect of these compounds in SW480 and SW620 colon cancer cell lines.     

Effects of Artonin E on Cell Growth Inhibition and Apoptosis Induction in Colon Cancer LoVo and HCT116 Cells

Today, colon cancer is the leading cause of cancer death. In Thailand, colon cancer is the third most common cancer in men and the second in women. Currently, the treatments for colon cancer include surgery, chemotherapy, radiation therapy, immunotherapy, hormone therapy, targeted drug therapy, and stem cell therapy. However, some treatments have side effects for cancer patients, causing unwanted symptoms. In addition, targeted therapy comes with a high cost for patients. Therefore, bioactive compounds might be a good choice for colon cancer treatment. In this study, we investigated the effect of artonin E on apoptosis induction in colon cancer LoVo and HCT116 cells. The concentration ranges of artonin E at 3, 5, 10, and 30 µg/mL in LoVo cells and 1, 1.5, 2, and 3 µg/mL in HCT116 cells were examined. The results implied that artonin E decreased cell viability and increased apoptotic cells in a dose-dependent manner. In addition, artonin E stimulated mitochondrial membrane potential (ΔΨm) changes associated with apoptosis by increasing the sub-G1 population analyzed by flow cytometry. Western blotting showed that artonin E increased the proapoptotic protein, Bax, and decreased anti-apoptotic proteins’ (Bcl-2 and Bcl-x) expression. Moreover, artonin E also increased cleaved caspase-7 and cleaved-PARP expression in both LoVo and HCT116 cells. Interestingly, artonin E induced apoptosis through p-ERK1/2, p-p38/p38, and p-c-Jun expression in both cells. Our results suggested that artonin E induced apoptosis via caspase activation associated with the MAPKs signaling pathway. Therefore, artonin E might be used as a potential anticancer drug for colon cancer in the future.     

MicroRNA-mediated Silencing of RhoC Inhibits Tumor Invasion and Increases Chemosensitivity to Paclitaxel in SKOV3 Cells in vitro

RhoC is a member of the Ras-homologous family of genes which are implicated in tumorigenesis and tumor progression. Up-regulation of RhoC is associated with tumor progression in ovarian carcinoma and RhoC is significantly correlated with the invasive capability of ovarian cancer cell lines in vitro. We developed a system that blocks RhoC in the human ovarian cancer SKOV3 cells using specific MicroRNA(miRNA) interference. By transfecting SKOV3 cells with the plasmid vector to express specific MiRNA that targ...     

Anti-Inflammatory Comparison of Melatonin and Its Bromobenzoylamide Derivatives in Lipopolysaccharide (LPS)-Induced RAW 264.7 Cells and Croton Oil-Induced Mice Ear Edema

The pineal gland is a neuroendocrine organ that plays an important role in anti-inflammation through the hormone melatonin. The anti-inflammatory effects of melatonin and its derivatives have been reported in both in vitro and in vivo models. Our previous study reported the potent antioxidant and neuroprotective activities of bromobenzoylamide substituted melatonin. In silico analysis successfully predicted that melatonin bromobenzoylamid derivatives were protected from metabolism by CYP2A1, which is a key enzyme of the melatonin metabolism process. Therefore, the anti-inflammatory activities of melatonin and its bromobenzoylamide derivatives BBM and EBM were investigated in LPS-induced RAW 264.7 macrophages and croton oil-induced ear edema in mice. The experiments showed that BBM and EBM significantly reduced production of the inflammatory mediators interleukin-6 (IL-6), prostaglandin E2 (PGE₂), and nitric oxide (NO) in a dose-dependent manner, but only slightly affected TNF-α in LPS-induced RAW 264.7 macrophages. This suggests that modifying melatonin at either the N1-position or the N-acetyl side chain affected production of NO, PGE₂ and IL-6 in in vitro model. In the croton oil-induced mouse ear edema model, BBM, significantly decreased ear edema thickness at 2–4 h. It leads to conclude that bromobenzoylamide derivatives of melatonin may be one of the potential candidates for a new type of anti-inflammatory agent.     

Natural Phenolic Acid,Product of the Honey Bee,for the Control of Oxidative Stress,Peritoneal Angiogenesis,and Tumor Growth in Mice

Tumor-associated macrophages (TAM) are key regulators of the link between inflammation and cancer, and the interplay between TAM and tumor cells represents a promising target of future therapeutic approaches. We investigated the effect of gallic acid (GA) and caffeic acid (CA) as strong antioxidant and anti-inflammatory agents on tumor growth, angiogenesis, macrophage polarization, and oxidative stress on the angiogenic model caused by the intraperitoneal (ip) inoculation of Ehrlich ascites tumor (EAT) cells (2.5 × 10⁶) in Swiss albino mouse. Treatment with GA or CA at a dose of 40 mg/kg and 80 mg/kg ip was started in exponential tumor growth phase on days 5, 7, 9, and 11. On day 13, the ascites volume and the total number and differential count of the cells present in the peritoneal cavity, the functional activity of macrophages, and the antioxidant and anti-angiogenic parameters were determined. The results show that phenolic acids inhibit the processes of angiogenesis and tumor growth, leading to the increased survival of EAT-bearing mice, through the protection of the tumoricidal efficacy of M1 macrophages and inhibition of proangiogenic factors, particularly VEGF, metalloproteinases -2 and -9, and cyclooxygenase-2 activity.     

Resveratrol Enhances Inhibition Effects of Cisplatin on Cell Migration and Invasion and Tumor Growth in Breast Cancer MDA-MB-231 Cell Models In Vivo and In Vitro

Triple-negative breast cancer (TNBC) is a refractory type of breast cancer that does not yet have clinically effective drugs. The aim of this study is to investigate the synergistic effects and mechanisms of resveratrol combined with cisplatin on human breast cancer MDA-MB-231 (MDA231) cell viability, migration, and invasion in vivo and in vitro. In vitro, MTS assays showed that resveratrol combined with cisplatin inhibits cell viability as a concentration-dependent manner, and produced synergistic effects (CI < 1). Transwell assay showed that the combined treatment inhibits TGF-β1-induced cell migration and invasion. Immunofluorescence assays confirmed that resveratrol upregulated E-cadherin expression and downregulated vimentin expression. Western blot assay demonstrated that resveratrol combined with cisplatin significantly reduced the expression of fibronectin, vimentin, P-AKT, P-PI3K, P-JNK, P-ERK, Sma2, and Smad3 induced by TGF-β1 (p < 0.05), and increased the expression of E-cadherin (p < 0.05), respectively. In vivo, resveratrol enhanced tumor growth inhibition and reduced body weight loss and kidney function impairment by cisplatin in MDA231 xenografts, and significantly reduced the expressions of P-AKT, P-PI3K, Smad2, Smad3, P-JNK, P-ERK, and NF-κB in tumor tissues (p < 0.05). These results indicated that resveratrol combined with cisplatin inhibits the viability of breast cancer MDA231 cells synergistically, and inhibits MDA231 cells invasion and migration through Epithelial-mesenchymal transition (EMT) approach, and resveratrol enhanced anti-tumor effect and reduced side of cisplatin in MDA231 xenografts. The mechanism may be involved in the regulations of PI3K/AKT, JNK, ERK and NF-κB expressions.     

Anticancer Effects of Ursi Fel Extract and Its Active Compound,Ursodeoxycholic Acid,in FRO Anaplastic Thyroid Cancer Cells

Anaplastic thyroid cancer (ATC) is one of the most fatal human malignancies. Ursi Fel (UF) is the bile of a brown bear that has been traditionally used for heat clearance and toxin relief in Korean and Chinese medicines. In this study, we determined the anticancer effects of a UF extract and its active compound, ursodeoxycholic acid (UDCA), in FRO human ATC cells. FRO cells were treated with UF extract and UDCA at different concentrations for various durations. Cell viability was measured using an MTT assay. Cell apoptosis was investigated by flow cytometric analysis following Annexin V and propidium iodide (PI) staining, and Hoechst staining was used to observe nuclear fragmentation. The expression of pro-apoptotic (Bax, caspase-3, cytochrome c, and PARP), anti-apoptotic (Bcl-2), and angiogenetic (TGF-β, VEGF, N-cadherin, and sirtuin-1) proteins and the phosphorylation of Akt and mechanistic target of rapamycin (mTOR) were determined by western blot analysis. Treatment with UF extract at 10, 25, and 50 μg/mL and UDCA at 25, 50, and 100 μM/mL significantly inhibited the growth of FRO cells in a dose-dependent manner. Flow cytometry and Hoechst staining revealed an increase in the apoptosis of FRO cells mediated by UF extract and UDCA in a dose-dependent manner. UF extract (25 and 50 μg) and UDCA (50 and 100 μM) significantly increased the expression of Bax, caspase-3, cytochrome c, and PARP and inhibited the expression of Bcl-2, TGF-β, VEGF, N-cadherin, and sirtuin-1 in FRO cells. Furthermore, UF extract and UDCA treatment stimulated Akt phosphorylation and inhibited mTOR phosphorylation in these cells. These results indicate that UF extract and UDCA exert anticancer properties in FRO cells by inducing apoptosis and inhibiting angiogenesis via regulating the Akt/mTOR signaling pathway.     

Broussochalcone A Is a Novel Inhibitor of the Orphan Nuclear Receptor NR4A1 and Induces Apoptosis in Pancreatic Cancer Cells

The orphan nuclear receptor 4A1 (NR4A1) is overexpressed in pancreatic cancer and exhibits pro-oncogenic activity, and NR4A1 silencing and treatment with its inactivators has been shown to inhibit pancreatic cancer cells and tumor growth. In this study, we identified broussochalcone A (BCA) as a new NR4A1 inhibitor and demonstrated that BCA inhibits cell growth partly by inducing NR4A1-mediated apoptotic pathways in human pancreatic cancer cells. BCA downregulated specificity protein 1 (Sp1)-mediated expression of an anti-apoptotic protein, survivin, and activated the endoplasmic reticulum (ER) stress-mediated apoptotic pathway. These results suggest that NR4A1 inactivation contributes to the anticancer effects of BCA, and that BCA represents a potential anticancer agent targeting NR4A1 that is overexpressed in many types of human cancers.     

Treatment with Uncaria tomentosa Promotes Apoptosis in B16-BL6 Mouse Melanoma Cells and Inhibits the Growth of B16-BL6 Tumours

Uncaria tomentosa is a medicinal plant native to Peru that has been traditionally used in the treatment of various inflammatory disorders. In this study, the effectiveness of U. tomentosa as an anti-cancer agent was assessed using the growth and survival of B16-BL6 mouse melanoma cells. B16-BL6 cell cultures treated with both ethanol and phosphate-buffered saline (PBS) extracts of U. tomentosa displayed up to 80% lower levels of growth and increased apoptosis compared to vehicle controls. Treatment with ethanolic extracts of Uncaria tomentosa were much more effective than treatment with aqueous extracts. U. tomentosa was also shown to inhibit B16-BL6 cell growth in C57/bl mice in vivo. Mice injected with both the ethanolic and aqueous extracts of U. tomentosa showed a 59 ± 13% decrease in B16-BL6 tumour weight and a 40 ± 9% decrease in tumour size. Histochemical analysis of the B16-BL6 tumours showed a strong reduction in the Ki-67 cell proliferation marker in U. tomentosa-treated mice and a small, but insignificant increase in terminal transferase dUTP nick labelling (TUNEL) staining. Furthermore, U. tomentosa extracts reduced angiogenic markers and reduced the infiltration of T cells into the tumours. Collectively, the results in this study concluded that U. tomentosa has potent anti-cancer activity that significantly inhibited cancer cells in vitro and in vivo.     

Synthesis of Novel Methyl 7-[(Hetero)arylamino]thieno[2,3-b]pyrazine-6-carboxylates and Antitumor Activity Evaluation: Effects in Human Tumor Cells Growth,Cell Cycle Analysis,Apoptosis and Toxicity in Non-Tumor Cells

Several novel methyl 7-[(hetero)arylamino]thieno[2,3-b]pyrazine-6-carboxylates were synthesized by Pd-catalyzed C–N Buchwald–Hartwig cross-coupling of either methyl 7-aminothieno[3,2-b]pyrazine-6-carboxylate with (hetero)arylhalides or 7-bromothieno[2,3-b]pyrazine-6-carboxylate with (hetero)arylamines in good-to-excellent yields (50% quantitative yield), using different reaction conditions, namely ligands and solvents, due to the different electronic character of the substrates. The antitumoral potential of these compounds was evaluated in four human tumor cell lines: gastric adenocarcinoma (AGS), colorectal adenocarcinoma (CaCo-2), breast carcinoma (MCF7), and non-small-cell lung carcinoma (NCI-H460) using the SRB assay, and it was possible to establish some structure–activity relationships. Furthermore, they did not show relevant toxicity against a non-tumor cell line culture from the African green monkey kidney (Vero). The most promising compounds (GI₅₀ ≤ 11 µM), showed some selectivity either against AGS or CaCo-2 cell lines without toxicity at their GI₅₀ values. The effects of the methoxylated compounds 2b (2-OMeC₆H₄), 2f and 2g (3,4- or 3,5-diOMeC₆H₃, respectively) on the cell cycle profile and induction of apoptosis were further studied in the AGS cell line. Nevertheless, even for the most active (GI₅₀ = 7.8 µM) and selective compound (2g) against this cell line, it was observed that a huge number of dead cells gave rise to an atypical distribution on the cell cycle profile and that these cells were not apoptotic, which points to a different mechanism of action for the AGS cell growth inhibition.