Intraperitoneal BromAc® Does Not Interfere with the Healing of Colon Anastomosis.

A combination of bromelain and acetylcysteine, BromAc®, is an efficient intraperitoneal mucolytic for thick mucus secreted in pseudomyxoma peritonei (PMP). Patients with PMP quite often undergo colon anastomosis. Hence, we investigated the effect of the intraperitoneal delivery of BromAc® on colon-anastomosis healing in a rat model. Sixteen Wistar rats were divided into two groups (N = 8). The controls received intraperitoneal saline after anastomosis, whilst the other group received BromAc®. They were monitored for body-weight and general health parameters. Half the rats in each group (N = 4) were culled at 4 or 13 days post-surgery for assessment. The healing process of the tissues was assessed by burst pressure and collagen density with histology to assess the integrity of the internal organs. The results indicated that there was a similar pattern of weight fluctuation during the experiment, although the rats treated with the BromAc® showed slightly greater weight loss during the first 4 days. Although the burst pressure was similar in both groups, the BromAc® group at day 13 showed a slightly higher burst pressure, which was complemented by a higher collagen density (albeit not statistically significant). The histology of the internal organs was comparable to those of the controls. This study indicates that the intraperitoneal delivery of BromAc® in a rat model does not interfere with the healing process of colonic anastomosis.

Physical and chemical factors affecting the loading and release of bromelain from DC beads.

Doxorubicin loaded DC beads (microspheres) has been used for treating un-resectable tumours by transarterial chemoembolization (TACE). We have shown that bromelain, an enzyme from the pineapple plant, enhances the cytotoxic effect of a number of chemotherapeutic drugs and in an earlier study we have demonstrated that it can be loaded into DC beads. Therefore, in the current study we have investigated how certain physical and chemical parameters affect its loading and release for future development of DC beads in cancer therapy. Aliquots of 40-60 µL of DC beads (100-300 µm) were treated to bromelain in distilled water and various parameters such as pH of solution, bromelain concentration, temperature, loading period, presence/absence of agitation and the cytotoxic effect of bromelain loaded beads were investigated. Further release kinetics was also studied with additional investigation of pH effect on the proteolytic activity of bromelain. Results indicate that higher loading of bromelin was achieved in the beads at lower pH, higher concentration of bromelain, with agitation, 24 hours loading and ambient room temperature. Proteolytic activity of bromelain was maximal at pH 4.5 whilst cytotoxicity was at par if not better in the bromelain loaded DC beads. Release kinetics indicated that bromelain can be delivered over several hours. Hence, we conclude that bromelain can be loaded more efficiently with manipulation of certain parameters with noticeable cytotoxicity in tumour cells.

A novel method for potentiation of chemotherapy in soft tissue sarcomas with BromAc.

Single-agent doxorubicin currently forms part of standard care for patients with sarcomas. However, efficacy is limited by the presence of dose-dependent cardiotoxicity and toxicity to renal, hepatic, and neurological systems. Therefore, there is a pressing need for novel drug regimens which can provide increased efficacy and safety. BromAc is a novel drug combination developed as a mucolytic agent which has demonstrated anticancer activity both in vitro and in vivo in several cancers. Here, we investigated the efficacy of BromAc in combination with doxorubicin for four subtypes of sarcoma. Cell proliferation, alongside western blot for a variety of cell cycle, apoptosis, and autophagy biomarkers assays was performed following treatment of cell lines in vitro at various concentrations of BromAc and doxorubicin. The impact of drug treatment on MUC1 and MUC4 levels was assessed through immune-cytological methods. Drug agent synergy was assessed through the Chou-Talalay framework. BromAc treatment in combination with doxorubicin was more efficacious than single-agent doxorubicin, with synergistic effects observed. The immuno-cytological analysis demonstrated significant mucin depletion following treatment with BromAc and doxorubicin used in combination, providing a potential mechanistic underpinning for the observed anticancer effects.

Monepantel antitumor activity is mediated through inhibition of major cell cycle and tumor growth signaling pathways.

In women, epithelial ovarian cancer is the leading cause of gynaecological malignancy-related deaths. Development of resistance to standard platinum and taxane based chemotherapy and recurrence of the disease necessitate development of novel drugs to halt disease progression. An established concept is to target molecular and signaling pathways that substantially contribute to development of drug resistance and disease progression. We have previously shown that, monepantel (MPL) a novel small molecule acetonitrile derivative is highly effective in suppressing growth, proliferation and colony formation of ovarian cancer cells. These effects are achieved through inhibition of the mTOR/p70S6K pathway in cancer cells. The present study was conducted to find in vivo corroboration and explore the effect of MPL om other growth stimulating putative signaling pathways. Here, female nude mice with subcutaneous OVCAR-3 xenografts were treated with 25 and 50 mg/kg doses of MPL administered (IP) three times weekly for 2 weeks. At the doses employed, MPL was modestly effective at suppressing tumor growth, but highly effective in inhibiting, mTOR, P70S6K and 4EBP1. There were also modest reductions in tumor cyclin D1 and retinoblastoma protein expression. Furthermore, it was found that MPL treatment causes down-regulation of IGF-1R, and c-MYC thus unveiling new dimensions to the growing antitumor actions of this potential anticancer drug. MPL treatment led to reduced tumor volume and weights without causing any detectable side effects. Coupled with the recent human safety data published on this molecule, expanded future trials are highly anticipated.

Comparison of proteolytic, cytotoxic and anticoagulant properties of chromatographically fractionated bromelain to un-fractionated bromelain.

Bromelain consisting of a number of proteolytic enzymes possess anticancer and thrombotic properties. Hence, four chromatically separated fractions were examined for their proteolytic, anticancer and antithrombotic activity. Bromelain fractions were separated using ion-exchange column chromatography. Proteolytic properties were assessed using standard azocasein assay. Anticancer properties were first assessed using four different cell lines PANC-1, HEP 2B, HEP 3G and OVCAR-3 on cells grown in 96 well plates. Subsequently, fraction 2 and fraction 3 combined with gemcitabine were tested in ASPC-1 cells. Then cytotoxicity of fraction 3 was compared to bromelain in combination with doxorubicin and N-acetylcysteine on HEP G2 and HEP 3B cells. Finally, the anticoagulation effect of fraction 3 or bromelain combined with N-acetylcysteine was evaluated using human blood. Fraction 3 showed the highest proteolytic activity (5% greater than standard bromelain) whilst others were less active. Cytotoxicity as assessed by IC50 indicated fraction 3 to be the most potent whilst the others did not follow their proteolytic potency order. OVCAR-3 was the most sensitive amongst the cell lines. Fraction 3 showed higher potency in combination with gemcitabine in ASPC-1 cells compared to fraction 2. Similarly, fraction 3 in combination with doxorubicin showed higher toxicity when compared to bromelain. Fraction 3 or bromelain only showed thrombolytic activity in combination with N-acetylcysteine. Fraction 3 may be developed for clinical use since it showed better cytotoxicity compared to bromelain.

Addition of bromelain and acetylcysteine to gemcitabine potentiates tumor inhibition in vivo in human colon cancer cell line LS174T.

The combinations of Bromelain and Acetylcysteine (BromAc®) with cytotoxics such as Gemcitabine, 5-Fluorouracil or Oxaliplatin have shown a dramatic reduction in IC50 values in a variety of cancers, including colon cancer, suggesting the possibility of effective treatment without undesired side effects. In the current study, we investigated whether a similar effect is present in vivo using the colorectal cell line LS174T. Animals after acclimatization were randomized and allocated equally in the groups for the different studies (safety, dose-escalation, and efficacy). Drugs were delivered by the intraperitoneal route and animals were monitored for wellbeing. Separately, an efficacy study was conducted with intraperitoneal drug delivery after intraperitoneal tumor induction. At the termination of the experiment, tumors and other tissues were collected for evaluation. BromAc® was safe when delivered intraperitoneally in a rat model at the concentrations used. Subsequent investigations of these adjuvants in combination with Gemcitabine, Oxaliplatin, and 5-Fluorouracil in mice were also proven to be safe. Preliminary efficacy studies with Oxaliplatin and 5-Fluorouracil on tumor growth (LS174T) were negative. Gemcitabine was assessed with BromAc® showing an almost 71% tumor inhibition compared to controls. This in vivo study indicates that Gemcitabine at 2 mg/kg in combination with BromAc® 3 mg/300 mg/Kg was effective and safe, supporting its potential for future clinical application.

The Combination of Bromelain and Acetylcysteine (BromAc) Synergistically Inactivates SARS-CoV-2.

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is the cause of a worldwide pandemic, currently with limited therapeutic options. The spike glycoprotein and envelope protein of SARS-CoV-2, containing disulfide bridges for stabilization, represent an attractive target as they are essential for binding to the ACE2 receptor in host cells present in the nasal mucosa. Bromelain and Acetylcysteine (BromAc) has synergistic action against glycoproteins by breakage of glycosidic linkages and disulfide bonds. We sought to determine the effect of BromAc on the spike and envelope proteins and its potential to reduce infectivity in host cells. Recombinant spike and envelope SARS-CoV-2 proteins were disrupted by BromAc. Spike and envelope protein disulfide bonds were reduced by Acetylcysteine. In in vitro whole virus culture of both wild-type and spike mutants, SARS-CoV-2 demonstrated a concentration-dependent inactivation from BromAc treatment but not from single agents. Clinical testing through nasal administration in patients with early SARS-CoV-2 infection is imminent.

The effect of intraperitoneal administration of BromAc on blood parameters: phase 1 study.

Intraperitoneal administration of BromAc (bromelain + acetylcysteine) is currently undergoing a phase 1 clinical trial for pseudomyxoma peritonei at our institution. This study reports on analysis of routine blood parameters before and after treatment for a series of 25 patients in this trial. Blood parameters assessed included full blood count, electrolytes, urea, and creatinine, liver function tests, coagulation studies, as well as inflammatory markers (CRP). Certain parameters such as CRP, and white cell count, were significantly elevated after treatment whilst serum albumin level was reduced indicating an inflammatory reaction. However, liver enzymes, coagulation studies, and other parameters were not affected. Therefore, there are no additional safety signals evident upon analysis of routine blood parameter testing.

Bromelain and acetylcysteine (BromAc®) alone and in combination with gemcitabine inhibit subcutaneous deposits of pancreatic cancer after intraperitoneal injection.

Gemcitabine (GEM) is commonly chosen for treating pancreatic cancer. However, its use is limited by toxicity. Earlier in vitro studies with GEM in combination with Bromelain (Brom) and Acetylcysteine (Ac) indicated a substantial reduction in IC50. In this study, immunocytochemistry and Western blot were used to explore the mechanistic effects of Brom and Ac (BromAc®) in vitro. Then, we explored the efficacy and safety of BromAc® only and with GEM in a pancreatic cancer model in vivo. Immunocytochemistry results revealed a reduction in both MUC1 and MUC4 post-treatment. There was a decrease in VEGF, MMP-9, NF-κß and cleavage of PARP. There was also a decrease in the cell cycle regulators Cyclin B and D as well as TGF-ß and the anti-apoptotic Bcl-2. In vivo, the low and high doses of BromAc® alone and with chemotherapy agents were safe. A very significant reduction in pancreatic tumour volume, weight, and ki67 were seen with BromAc® therapy and was equal to treatment with GEM alone and better than treatment with 5-FU. In addition, tumour density was significantly reduced by BromAc®. In conclusion, the anticancer effect of BromAc® is probably related to its mucin depletion activity as well as its effect on proteins involved in cell cycle arrest, apoptosis and modulation of the tumour microenvironment. The in vivo results are encouraging and are considered the first evidence of the efficacy of BromAc® in pancreatic cancer. These results also provide some mechanistic leads of BromAc®.

Enhancing the potency of chemotherapeutic agents by combination with bromelain and N-acetylcysteine - an in vitro study with pancreatic and hepatic cancer cells.

Current systemic dosages of chemotherapeutic drugs such as gemcitabine, 5-FU, cisplatin, doxorubicin are administered every 7 days over 4 cycles due to systemic toxicity. An increase in potency of the drugs will result in dosage reduction with more frequent administration and efficacy increase. Hence, we investigated how the drugs potency can be increased by combining with bromelain and N-acetylcysteine. Tumour cells (5,000/well) were seeded into a 96 well plate and treated 24 hrs later with either single agents or in combinations at various concentrations. Cell survival was assessed by the sulforhodamine B assay after 72 hours of exposure. LD 50 was determined for each treatment and the Combination Index (CI) was assessed to determine synergy using Tallarida's method. CI indicated that synergy was dependent on the concentration of the agents used and was cell line specific. For bromelain and N-acetylcysteine, certain ratio of the two agents gave very good synergy that was prevalent in almost all cell lines. Gemcitabine and 5-FU and doxorubicin reacted favourably with most concentrations of bromelain and NAC investigated. Cisplatin and oxaliplatin were not very compatible with NAC. A value of CI <0.5 indicated that the current clinical chemotherapeutic dosage can be dramatically reduced. Bromelain with NAC showed synergy in all tumour cell lines and acting synergistically with chemotherapeutic drugs. Synergistic combinations resulting in considerable dosage reduction of chemotherapeutic agents may enable more frequent treatment with higher efficacy.

Monepantel considerably enhances the therapeutic potentials of PEGylated liposomal doxorubicin and gemcitabine in ovarian cancer: in vitro and in vivo studies.

Ovarian cancer is a lethal disease since treated patients often die from relapse. Resistance to current treatment regime involving doxorubicin and gemcitabine is well known. Hence, we set forth to develop a more effective therapy by combining current treatment drugs with monepantel, an antihelminth drug with proven anticancer effect. In vitro cytotoxicity were first investigated with pegylated liposomal doxorubicin (PLD), gemcitabine, monepantel as single agents and then in combination with monepantel on ovarian tumor cells. Drug effect on oncogenic proteins was determined by western blot analysis and resistance to drugs by colony formation assays. Using in vivo model (nude mice), a similar study, as above, was carried out to determine correlation to in vitro findings. Close correlation existed between in vitro and in vivo studies with the latter indicating that combination of monepantel with either low or high dose PLD was more effective compared to single drug therapy. A similar finding existed for gemcitabine, with gemcitabine showing a more superior efficacy (100% ablation) in combination with MPL. Western blot analysis indicated p-mTOR, p70s6K and 4E-BP1 were severely inhibited by combination of MPL with either PLD or gemcitabine. Colony formation assay indicated a dramatic reduction of colonies with combination treatment suggesting a considerable reduction of resistance. After 28 days, treatment using a combination of MPL with either PLD or gemcitabine showed tumor regression. Hence, the combination of gemcitabine or doxorubicin with monepantel may serve as a more effective therapy for ovarian cancer.

Minocycline attenuates hypoxia-inducible factor-1α expression correlated with modulation of p53 and AKT/mTOR/p70S6K/4E-BP1 pathway in ovarian cancer: in vitro and in vivo studies.

Hypoxia-inducible factor (HIF)-1α is the key cellular survival protein under hypoxia, and is associated with tumor progression and angiogenesis. We have recently shown the inhibitory effects of minocycline on ovarian tumor growth correlated with attenuation of vascular endothelial growth factor (VEGF) and herein report a companion laboratory study to test if these effects were the result of HIF-1α inhibition. In vitro, human ovarian carcinoma cell lines (A2780, OVCAR-3 and SKOV-3) were utilized to examine the effect of minocycline on HIF-1 and its upstream pathway components to elucidate the underlying mechanism of action of minocycline. Mice harboring OVCAR-3 xenografts were treated with minocycline to assess the in vivo efficacy of minocycline in the context of HIF-1. Minocycline negatively regulated HIF-1α protein levels in a concentration-dependent manner and induced its degradation by a mechanism that is independent of prolyl-hydroxylation. The inhibition of HIF-1α was found to be associated with up-regulation of endogenous p53, a tumor suppressor with confirmed role in HIF-1α degradation. Further studies demonstrated that the effect of minocycline was not restricted to proteasomal degradation and that it also caused down-regulation of HIF-1α translation by suppressing the AKT/mTOR/p70S6K/4E-BP1 signaling pathway. Minocycline treatment of mice bearing established ovarian tumors, led to suppression of HIF-1α accompanied by up-regulation of p53 protein levels and inactivation of AKT/mTOR/p70S6K/4E-BP1 pathway. These data reveal the therapeutic potential of minocycline in ovarian cancer as an agent that targets the pro-oncogenic factor HIF-1α through multiple mechanisms.

Minocycline targets the NF-κB Nexus through suppression of TGF-ß1-TAK1-IκB signaling in ovarian cancer.

UNLABELLED: Substantial evidence supports the critical role of NF-κB in ovarian cancer. Minocycline, a tetracycline, has been shown to exhibit beneficial effects in this malignancy through regulation of a cohort of genes that overlap significantly with the NF-κB transcriptome. Here, it was examined whether or not the molecular mechanism could be attributed to modulation of NF-κB signaling using a combination of in vitro and in vivo models. Minocycline suppressed constitutive NF-κB activation in OVCAR-3 and SKOV-3 ovarian carcinoma cells and was correlated with attenuation of IκBα kinase (IKK) activation, IκBα phosphorylation and degradation, and p65 phosphorylation and nuclear translocation. The inhibition of IKK was found to be associated with suppression of TGF-ß-activated-kinase-1 (TAK1) activation and its dissociation from TAK1-binding-protein-1 (TAB1), an indispensable functional mediator between TGF-ß and TAK1. Further studies demonstrated that minocycline downregulated TGF-ß1 expression. Enforced TGF-ß1 expression induced NF-κB activity, and minocycline rescued this effect. Consistent with this finding, TGF-ß1 knockdown suppressed NF-κB activation and abrogated the inhibitory effect of minocycline on this transcription factor. These results suggest that the minocycline-induced suppression of NF-κB activity is mediated, in part, through inhibition of TGF-ß1. Furthermore, the influence of minocycline on NF-κB pathway activation was examined in female nude mice harboring intraperitoneal OVCAR-3 tumors. Both acute and chronic administration of minocycline led to suppression of p65 phosphorylation and nuclear translocation accompanied by downregulation of NF-κB activity and endogenous protein levels of its target gene products. These data reveal the therapeutic potential of minocycline as an agent targeting the pro-oncogenic TGF-ß-NF-κB axis in ovarian cancer. IMPLICATIONS: This preclinical study lends support to the notion that ovarian cancer management would benefit from administration of minocycline.

Minocycline inhibits malignant ascites of ovarian cancer through targeting multiple signaling pathways.

OBJECTIVES: To evaluate the effect of minocycline on the expression of cytokines and growth factors responsible for malignant ascite formation. METHODS: In vitro, cells obtained from malignant ascites were pre-treated with minocycline (0-100 µmol/L) and exposed briefly to hypoxia. In vivo, female nude mice bearing OVCAR-3 tumors were treated orally in drinking water with minocycline for 4 weeks. Plasma, ascites, and tumors were analyzed. RESULTS: Minocycline blocked hypoxia-induced surge in interleukin-6 (IL-6), its soluble receptor (sIL-6R) and vascular endothelial growth factor (VEGF) levels in concentration-dependent manner. In mice, orally administered minocycline led to dramatic reduction in tumor weight and malignant ascite volume. IL-6, sIL6R and in particular VEGF levels were highly suppressed in plasma, ascite fluid and tumor tissue by minocycline. In addition, tumors from minocycline treated mice expressed profoundly lower levels of phosphorylated extracellular regulated kinases (p-Erk1/2) and p-Akt. Minocycline was also effective at suppressing transforming growth factor beta (TGF-ß1) and increasing vascular endothelial cadherin (VE-cadherin) expression thereby providing molecular confirmation for its effects on malignant ascite formation. CONCLUSION: Orally administered minocycline is highly effective in suppressing ovarian cancer-induced malignant ascites by targeting cytokines and growth factors essential for tumor growth and malignant ascite formation.

Minocycline inhibits growth of epithelial ovarian cancer.

OBJECTIVE: These studies were designed to determine whether minocycline inhibits ovarian cancer growth in vitro and in vivo and the molecular mechanisms involved. MATERIALS AND METHODS: The effect of minocycline on ovarian cancer cell proliferation, cell cycle progression and apoptosis was assessed using human ovarian cancer cell lines OVCAR-3, SKOV-3 and A2780. Then, the capacity of minocycline to inhibit growth of OVCAR-3 xenografts in female nude mice was examined. RESULTS: Minocycline inhibited cell proliferation and colony formation, down-regulated cyclins A, B and E leading to arrest of cells in the G(0) phase of the cycle and suppression of DNA synthesis. Furthermore, exposure of these cells to minocycline led to DNA laddering, activation of caspase-3 and cleavage of PARP-1. In nude mice bearing sub-cutaneous tumors, minocycline suppressed tumor proliferation index, angiogenesis and tumor growth. CONCLUSION: These findings provide the initial basis for further evaluation of minocycline in the treatment of ovarian cancer.

Albendazole inhibits endothelial cell migration, tube formation, vasopermeability, VEGF receptor-2 expression and suppresses retinal neovascularization in ROP model of angiogenesis.

The angiogenic process begins with the cell proliferation and migration into the primary vascular network, and leads to vascularization of previously avascular tissues and organs as well to growth and remodeling of the initially homogeneous capillary plexus to form a new microcirculation. Additionally, an increase in microvascular permeability is a crucial step in angiogenesis. Vascular endothelial growth factor (VEGF) plays a central role in angiogenesis. We have previously reported that albendazole suppresses VEGF levels and inhibits malignant ascites formation, suggesting a possible effect on angiogenesis. This study was therefore designed to investigate the antiangiogenic effect of albendazole in non-cancerous models of angiogenesis. In vitro, treatment of human umbilical vein endothelial cells (HUVECs) with albendazole led to inhibition of tube formation, migration, permeability and down-regulation of the VEGF type 2 receptor (VEGFR-2). In vivo albendazole profoundly inhibited hyperoxia-induced retinal angiogenesis in mice. These results provide new insights into the antiangiogenic effects of albendazole.

Potent inhibition of tumoral hypoxia-inducible factor 1alpha by albendazole.

BACKGROUND: Emerging reports suggest resistance, increased tumor invasiveness and metastasis arising from treatment with drugs targeting vascular endothelial growth factor (VEGF). It is believed that increased tumoral hypoxia plays a prominent role in the development of these phenomena. Inhibition of tumoral hypoxia inducible factor (HIF-1alpha) is thus becoming an increasingly attractive therapeutic target in the treatment of cancer. We hypothesized that the anti-VEGF effect of albendazole (ABZ) could be mediated through inhibition of tumoral HIF-1alpha. METHOD: In vitro, the effects of ABZ on HIF-1alpha levels in human ovarian cancer cells (OVCAR-3) were investigated using hypoxic chamber or desferrioxamine (DFO) induced-hypoxia. In vivo, the effects of ABZ (150 mg/kg, i.p., single dose) on the tumor levels of HIF-1alpha and VEGF protein and mRNA were investigated by western blotting, RT-PCR and real time-PCR. RESULTS: In vitro, ABZ inhibited cellular HIF-1alpha protein accumulation resulting from placement of cells under hypoxic chamber or exposure to DFO. In vivo, tumors excised from vehicle treated mice showed high levels of both HIF-1alpha and VEGF. Whereas, tumoral HIF-1alpha and VEGF protein levels were highly suppressed in ABZ treated mice. Tumoral VEGFmRNA (but not HIF-1alphamRNA) was also found to be highly suppressed by ABZ. CONCLUSION: These results demonstrate for the first time the effects of an acute dose of ABZ in profoundly suppressing both HIF-1alpha and VEGF within the tumor. This dual inhibition may provide additional value in inhibiting angiogenesis and be at least partially effective in inhibiting tumoral HIF-1alpha surge, tumor invasiveness and metastasis.

Potent inhibition of tubulin polymerisation and proliferation of paclitaxel-resistant 1A9PTX22 human ovarian cancer cells by albendazole.

BACKGROUND: Resistance to paclitaxel (PTX) is a major concern in treating ovarian cancer. Thus, agents effective in taxane-resistant tumours are highly sought. It has recently been shown that albendazole (ABZ) is a potent inhibitor of cell proliferation, angiogenesis and tumour growth. This study was designed to examine the efficacy of ABZ in PTX-resistant human ovarian cancer 1A9PTX22 cells. MATERIALS AND METHODS: Using both the parent PTX-sensitive 1A9 and PTX-resistant sub-line 1A9PTX22 cells, the effects of both drugs on cell proliferation, tubulin polymerisation and microtubule distribution across the cell was investigated. RESULTS: Comparison of the inhibitory concentration to achieve 50% cell death (IC(50)) revealed that, unlike PTX, ABZ is highly efficacious in inhibiting proliferation of 1A9PTX22 cells. The finding that ABZ but not PTX is highly effective in disrupting tubulin polymerisation in these cells confirmed involvement of the tubulin pathway. CONCLUSION: Data from this study suggest that ABZ is effective in suppressing growth of PTX-resistant ovarian tumour cells.

Inhibition of cell proliferation, vascular endothelial growth factor and tumor growth by albendazole.

Vascular endothelial growth factor (VEGF) is the key molecule mediating tumor growth and malignant ascites formation. We recently reported that, in an end stage OVCAR-3 xenograft model, albendazole (ABZ) suppresses ascites formation, but not tumor growth. Hence, in the present study, we assessed the effect of ABZ on in vitro OVCAR-3 cell proliferation plus in vivo tumor growth, however, initiating ABZ treatment at mid stage (3 weeks post cell inoculation) rather than end stage disease. Here, ABZ treatment led to potent inhibition of cell proliferation, VEGF suppression, complete inhibition of ascites formation and most strikingly arrest of tumor growth.