boron and Carcinoma--Hepatocellular

Boron neutron capture therapy (BNCT) is becoming a promising radiation treatment technique dealing with tumors due to its cellular targeting specificity. In this article, based on the biocompatible chitosan oligosaccharide (COS), we designed a boron delivery system using carborane (CB) as a boron drug with cRGD peptide modification and paclitaxel (PTX) loaded in the hydrophobic core. The nanoparticles (cRGD-COS-CB/PTX) realized the boron delivery into tumor sites with an enhanced permeability and retention (EPR) effect and an active targeting effect achieved by the cRGD-integrin interaction on the surface of tumor cells. The uniform spherical nanoparticles can be selectively taken by hepatoma cells rather than normal hepatocytes.

Topics: Boranes; Boron; Boron Neutron Capture Therapy; Carcinoma, Hepatocellular; Cell Line, Tumor; Humans; Liver Neoplasms; Oligosaccharides

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in the world. Poor prognosis of HCC patients is a major issue, thus, better treatment options for patients are required. Curcumin (Cur), hydrophobic polyphenol of the plant turmeric, shows anti-proliferative, apoptotic, and anti-oxidative properties. Boron is a trace element which is essential part of human nutrition. Sodium pentaborate pentahydrate (NaB), a boron derivative, is an effective agent against cancer. In the current study, we performed in vitro experiments and transcriptome analysis to determine the response of NaB, Cur, piperine (Pip) and their combination in two different HCC cell lines, HepG2 and Hep3B. NaB and Cur induced cytotoxicity in a dose and time dependent manner in HepG2 and Hep3B, whereas Pip showed no significant toxic effect. Synergistic effect of combined treatment with NaB, Cur and Pip on HCC cells was observed on cytotoxicity, apoptosis and cell cycle assay. Following in vitro studies, we performed RNA-seq transcriptome analysis on NaB, Cur and Pip and their combination on HepG2 and Hep3B cells. Transcriptome analysis reveals combined treatment of NaB, Cur and Pip induces anti-cancer activity in both of HCC cells.

Topics: Boron; Carcinoma, Hepatocellular; Cell Line; Curcumin; Humans; Liver Neoplasms

The possible anti-cancer properties of boron, a trace element for humans, have been demonstrated in various experimental and epidemiological studies, although the effects of boron on liver cancer are unclear. In the present study we evaluate the effects of boric acid on the cell lines of hepatocellular carcinoma (HCC) of the liver, as the leading form of liver cancer, for which a poorly-differentiated HCC cell line (Mahlavu cell line) was used.. The anti-cancer effect of boric acid was investigated with a cell viability assay, apoptosis analysis, cell migration analysis, cell morphology analysis, colony formation assay and 3D cell culture techniques. Also, the effect of boric acid on the AKT signaling pathway was determined through a western blot analysis.. Boric acid was found to reduce cell viability in a dose- and time-dependent manner, and decreased survival, colony formation ability, migration capability and HCC cell tumor spheroid growth in HCC cell lines, while also inducing apoptosis, autophagy and morphological alteration. Furthermore, boric acid inhibited AKT phosphorylation, and anticancer biological responses in HCC cells were observed only in cells in which AKT phosphorylation was suppressed by boric acid.. Our results suggest that boric acid might be a promising therapeutic candidate in hepatocellular carcinoma via the inhibition of AKT signaling pathway.

Topics: Apoptosis; Boric Acids; Boron; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Humans; Liver Neoplasms; Proto-Oncogene Proteins c-akt; Signal Transduction

Reactive oxygen species (ROS) regulate various cellular signaling pathways and play an important role in the occurrence and development of hepatocellular carcinoma (HCC). Excessive accumulation of ROS can promote HCC. Trace element boron has a wide range of biological effects, including anti-oxidation, anti-tumor, immune regulation and so on.. In this study, we investigated the anticancer effects of Sodium tetraborate decahydrate (NaB) in improving oxidative stress and regulating apoptosis in mouse HCC. HCC was induced by intraperitoneal injection of diethylnitrosamine (DEN) 25 mg/kg once at the age of 2 weeks and 100 mg/kg again at the age of 6 weeks in healthy C3H/HeN male mice. At 8 weeks of age, different concentrations of NaB were given intragastric treatment once a day for 20 weeks. Oxidative stress markers, antioxidant status and liver enzyme analysis were detected to evaluate the effectiveness of NaB in inhibiting cancer induction. The anticancer properties of NaB were confirmed by observing the liver index and morphology, and analyzing the expression of apoptotic genes and proteins. Our results showed that boron significantly reduced the production of ROS, and down-regulated the expression of the anti-apoptotic protein Bcl2 and up-regulated the expression of the pro-apoptotic proteins P53, Bax, and caspase 3.. Boron has great potential to reduce the effects of oxidative stress, which may help it inhibit the progression of HCC.

Topics: Animals; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Boron; Carcinoma, Hepatocellular; Caspase 3; Diethylnitrosamine; Liver Neoplasms; Male; Mice; Mice, Inbred C3H; Oxidative Stress; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Trace Elements; Tumor Suppressor Protein p53

Boron has an important potential for facilitating biological activity and for use in pharmaceutical drug design. Boron glycine monoester (BGM) and boron glycine diester (BGD) compounds containing boron atoms were synthesized and investigated their cytotoxic, oxidative stress, and antimicrobial activities on the HepG2 cancer cell line. The cytotoxic activity of newly synthesized boron compounds on hepatocellular carcinoma was determined by the MTT method for 48 h. Antioxidant (CAT, GSH), lipid peroxidation (MDA), and enzyme activity (ACP, ALP) analyses were determined by spectrophotometric methods in HepG2 cells. Antimicrobial activity was determined by the disk diffusion method. After 48 h of BGM and BGD application to HepG2 cells, we found the IC

Topics: Antioxidants; Boron; Boron Compounds; Carcinoma, Hepatocellular; Glycine; Humans; Liver Neoplasms

Boron neutron-capture therapy (BNCT) has been used to inhibit the growth of various types of cancers. In this study, we developed a. We prepared the. Biodistribution results have revealed that. Tumour growth suppression and cancer-cell-killing effect was observed from the morphological and pathological analyses of the

Topics: Animals; Boron; Boron Neutron Capture Therapy; Carcinoma, Hepatocellular; Disease Models, Animal; Emulsions; Liver Neoplasms; Papaver; Plant Oils; Rabbits; Seeds; Tissue Distribution

Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. Boron neutron capture therapy (BNCT) may provide an alternative therapy for HCC. This study investigated the therapeutic efficacy of boric acid (BA)-mediated BNCT for HCC in a rat model.. The pharmacokinetic and biodistribution of BA in N1S1 tumor-bearing rats were analyzed. Rats were injected with 25 mg B/kg body weight via tail veins before neutron irradiation at the Tsing Hua Open-pool Reactor, and the efficacy of BNCT was evaluated from the tumor size, tumor blood flow, and biochemical analyses.. HCC-bearing rats administered BNCT showed reductions in tumor size on ultrasound imaging, as well as an obvious reduction in the distribution of tumor blood flow. The lesion located in livers had disappeared on the 80th day after BNCT; a recovery of values to normal levels was also recorded.. BA-mediated BNCT is a promising alternative for liver cancer therapy since the present study demonstrated the feasibility of curing a liver tumor and restoring liver function in rats. Efforts are underway to investigate the histopathological features and the detailed mechanisms of BA-mediated BNCT.

Topics: Animals; Boric Acids; Boron; Boron Neutron Capture Therapy; Carcinoma, Hepatocellular; Disease Models, Animal; Liver; Liver Neoplasms; Male; Rats; Rats, Sprague-Dawley; Tissue Distribution

Hepatocellular carcinoma (HCC) is a common malignancy and the main cause of mortality in patients with chronic liver diseases. This study reports the inhibitory effect of boron on HCC induced in rats by administering thioacetamide (TAA) (0.03%) in drinking water for 400days. Boron (4mg/kg body weight) was administered orally after induction of carcinoma. Treatment was continued for 122days, and cell proliferation, histology and biochemistry of treated and control group of rats were studied. Proliferating cell nuclear antigen (PCNA), and [(3)H]-thymidine incorporation, which increased in rats exposed to carcinogen, significantly decreased after boron treatment. PCNA index decreased from 80 in HCC rats to 32 after boron treatment. In the control group, it was 20. Boron caused a dose-dependent decrease in carcinogen-induced [(3)H]-thymidine uptake by the rat hepatocyte. It could partially reverse the activity of selected biochemical indicators of hepatic damage, oxidative stress, selenium and serum retinol, which are depleted in liver cancer, and improved overall health of animal. The study implicates the elevated levels of mammalian molybdenum Fe-S containing flavin hydroxylases, which increase the free radical production and oxidative stress, consequently causing increased hepatic cell proliferation in HCC, and reports boron to ameliorate these changes in liver cancer.

Topics: Animals; Boron; Carcinoma, Hepatocellular; Cell Line, Tumor; Dose-Response Relationship, Drug; Down-Regulation; Female; Liver Neoplasms; Molybdenum; Oxidative Stress; Proliferating Cell Nuclear Antigen; Rats; Rats, Wistar; Treatment Outcome

Hepatocellular carcinoma (HCC) is one of the most difficult to cure with surgery, chemotherapy, or other combinational therapies. In the treatment of HCC, only 30% patients can be operated due to complication of liver cirrhosis or multiple intrahepatic tumours. Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between (10)B atoms and thermal neutrons, so it is necessary to accumulate a sufficient quantity of (10)B atoms in tumour cells for effective tumour cell destruction by BNCT. Water-in-oil-in-water (WOW) emulsion has been used as the carrier of anti-cancer agents on intra-arterial injections in clinical. In this study, we prepared (10)BSH entrapped WOW emulsion by double emulsifying technique using iodized poppy-seed oil (IPSO), (10)BSH and surfactant, for selective intra-arterial infusion to HCC, and performed simulations of the irradiation in order to calculate the dose delivered to the patients.. WOW emulsion was administrated with intra-arterial injections via proper hepatic artery on VX-2 rabbit hepatic tumour models. We simulated the irradiation of epithermal neutron and calculated the dose delivered to the tissues with JAEA computational dosimetry system (JCDS) at JRR4 reactor of Japan Atomic Research Institute, using the CT scans of a HCC patient.. The (10)B concentrations in VX-2 tumour obtained by delivery with WOW emulsion were superior to those by conventional IPSO mix emulsion. According to the rabbit model, the boron concentrations (ppm) in tumour, normal liver tissue, and blood are 61.7, 4.3, and 0.1, respectively. The results of the simulations show that normal liver biologically weighted dose is restricted to 4.9 Gy-Eq (CBE; liver tumour: 2.5, normal liver: 0.94); the maximum, minimum, and mean tumour weighted dose are 43.1, 7.3, and 21.8 Gy-Eq, respectively, in 40 min irradiation. In this study, we show that (10)B entrapped WOW emulsion could be applied to novel intra-arterial boron delivery carrier for BNCT, and we show the possibility to apply BNCT to HCC. We can irradiate tumours as selectively and safety as possible, reducing the effects on neighbouring healthy tissues.

Topics: Animals; Boron; Boron Neutron Capture Therapy; Carcinoma, Hepatocellular; Emulsions; Feasibility Studies; Infusions, Intra-Arterial; Liver Neoplasms, Experimental; Oils; Rabbits; Water

Hepatocellular carcinoma remains widely prevalent in tropical Africa and south-east Asia. At present, there are no effective treatments for hepatoma and its prognosis is extremely poor unless the tumor was diagnosed in an early stage and resected before metastasis. Therefore, boron neutron capture therapy (BNCT) may provide an alternative therapy for treatment of hepatocellular carcinoma. In this study, the intracellular concentrations of L-boronophenylalanine (BPA), sodium borocaptate (BSH) and boric acid (BA) were examined in human hepatoma HepG2 and liver Clone 9 cell cultures. With the use of 25 microgB/mL media of BPA, BSH and BA, the intracellular uptake of boron in HepG2 and Clone 9 cells was compared. The suitability of BPA, BSH and BA were further evaluated on the basis of organ-specific boron distribution in normal rat tissues. BPA, BSH and BA were administered via intraperitoneal injection into rats with corresponding boron concentrations of 7, 25, and 25mg/kg body weight, respectively. The accumulation rates of BPA, BSH and BA in HepG2 cells were higher than that of Clone 9 cells. Boron concentration in BPA, BSH and BA treated HepG2 cells were 1.8, 1.5, and 1.6-fold of Clone 9 cells at 4h, respectively. In both HepG2 and Clone 9 cells, although the concentration of boron in BPA-treated cells exceeded that in BA-treated ones, however, cells treated with BPA had similar surviving fraction as those treated with BA after neutron irradiation. The accumulation ratios of boron in liver, pancreas and kidney to boron in blood were 0.83, 4.16 and 2.47, respectively, in BPA treated rats, and 0.75, 0.35 and 2.89, respectively, in BSH treated rats at 3h after treatment. However, boron does not appear to accumulate specifically in soft tissues in BA treated rats. For in situ BNCT of hepatoma, normal organs with high boron concentration and adjacent to liver may be damaged in neutron irradiation. BPA showed high retention in pancreas and may not be a good drug for BNCT of hepatoma. BSH had higher retention in liver but low level in pancreas and spleen appears to be a better candidate BNCT drug for hepatoma. These preliminary results provide useful information on future application of BNCT for hepatoma.

Topics: Animals; Boric Acids; Borohydrides; Boron; Boron Compounds; Boron Neutron Capture Therapy; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Survival; Clone Cells; Hepatocytes; Humans; Liver Neoplasms; Phenylalanine; Radiation-Sensitizing Agents; Rats; Rats, Sprague-Dawley; Sulfhydryl Compounds; Tissue Distribution