Antineoplastic Property Research Articles

Evaluation of the antineoplastic property of prodigiosins and 5-fluorouracil in restraining the growth of Ehrlich solid tumors in mice.

Prodigiosins have been shown to have anticancer activities. 5-Fluorouracil (5-FU) is broadly used chemotherapeutic drug that treats different solid tumors including breast cancer but has low response rates and a variety of side effects. In this study, we evaluated the anticancer properties of prodigiosins in a murine model "Ehrlich tumor" and tested whether it can be added to 5-FU to potentiate its effects. Markers of oxidative stress; MDA, NO, and GSH levels were evaluated as well as antioxidant enzyme activities of CAT SOD, GR, and GPx. The levels of Bax, Bcl-2, PCNA, and NF-κB proteins were measured using ELISA kits. The mRNAs of p53 and Cdc2 and Casp3 were quantitatively measured by real-time PCR and ELISA respectively. Cell cycle analysis was performed using flow cytometery. Prodigiosins did not influence tumor volume. Prodigiosins have not induced oxidative stress while 5-FU did increase MDA, NO but decreased GSH levels. The combination prodigiosins and 5-FU did reduce oxidative stress markers; MDA, NO and increased GSH levels. Prodigiosins significantly increased CAT only while 5-FU did decreased SOD, CAT, GPx, and GR. The combination prodigiosins and 5-FU increased the levels of these enzymes again. Prodigiosins increased the Bax/Bcl-2 ratio while the combination deceased it. In conclusion, prodigiosins have pronounced anticancer properties but their combination with 5-FU decreased oxidative stress exerted by 5-FU but weakened the apoptotic effects of 5-FU. Prodigiosins could affect a key mechanism through which 5-FU exerts its tumor inhibitory effects.

Cucurbitacin E Triggers Cellular Senescence in Colon Cancer Cells via Regulating the miR-371b-5p/TFAP4 Signaling Pathway.

The induction of cellular senescence is considered as a potent strategy to suppress cancer progression. Cucurbitacin E (CE) belongs to the triterpenoids and has received substantial attention for its antineoplastic property. However, the function of CE on cellular senescence remained elusive. Herein, we revealed that CE significantly induced cellular senescence in colorectal cancer (CRC) cells. The CE effects on the cellular senescence in CRC cells were confirmed by observing the common features of the senescence, such as the enhanced activity of senescence-associated β-galactosidase, γ-H2AX positive staining, and upregulation of senescence-associated proteins including p53, p27, and p21. Moreover, CE exerted pro-senescent effects in CRC cells via attenuating the transcription factor activating enhancer-binding protein 4 (TFAP4) expression, and the ectopic expression of TFAP4 blocked the CE-induced senescence. Mechanistically, CE treatment caused a robust increase in miR-371b-5p, which markedly repressed TFAP4. In contrast, silencing of miR-371b-5p counteracted the percentages of CE-induced senescent cells from 37.49 ± 2.61 to 7.06 ± 0.91% in HCT-116 cells via derepressing TFAP4 to attenuate the expression of p53, p21, and p16. Altogether, these results demonstrated that dietary CE induces CRC cellular senescence via modulating the miR-371b-5p/TFAP4 axis and presents opportunities for potential therapeutic strategies against CRC.

Kampo Medicine for Intractable Brain and Neurological Diseases

In Japan, 147 types of oral Kampo extract products are covered by the public insurance system; however, to the best of our knowledge, there are no large-scale randomized clinical trials. Therefore, the level of evidence or these products is low compared with that for medicines that have been introduced as insurance reimbursement drugs through randomized clinical trials. However, when conventional western medical treatments have not been effective or when patients desire a more effective therapy, Kampo extract products are one of the treatment options. Kampo extract products involve the adding of crude drugs and comprise a multi-component system. Therefore, it may be effective for various symptoms. I recommend that specialists use these products as complementary alternative medicines. I also introduce the "Huaier extract granule," which is an orally bioavailable traditional Chinese medicine composed of granules containing an aqueous extract of Trametes robiniophila Murr (Huaier), a mushroom found on hardwood tree trunks, with potential immune-regulating activity. Huaier has immunity enhancement activity, such as antineoplastic property, as well as immunity regulating activity against diseases, such as asthma, psoriasis, and immunoglobulin A nephritis. Therefore, for some intractable diseases, especially when the disease is thought to involve an immune disorder, Huaier can be an additional treatment option.

Dysregulated expression of miR-642a-5p and its target receptor-interacting serine/threonine-protein kinase 1 contribute to the phycocyanin-mediated inhibitory function on non-small cell lung cancer

• miRNA variations were screened through high-throughput miRNA-seq. • miR-642a-5p was significantly increased by phycocyanin in NSCLC cells. • RIPK1 was a direct target of miR-642a-5p in NSCLC cells. • Phycocyanin inhibits NSCLC cell activities through miR-642a-5p/RIPK1/NF-κB axis. Phycocyanin, a type of functional food additive, is shown to exert antineoplastic property in non-small cell lung cancer (NSCLC). Our previous work demonstrated that phycocyanin could suppress the viability of NSCLC cells via regulating receptor-interacting serine/threonine-protein kinase 1 (RIPK1), but the underlying mechanism remains unknown. Herein, a high-throughput miRNA sequencing method was employed to further explore miRNA variations for the first time. 43 down-regulated and 18 up-regulated miRNAs displayed differential expressions after phycocyanin exposure. Particularly, the expression of miR-642a-5p was significantly increased by phycocyanin. Dual-luciferase assay revealed that RIPK1 was a direct target of miR-642a-5p. siRNA knockdown RIPK1 expression and overexpression of miR-642a-5p both inhibited cell proliferation, colony formation and NF-κB activity, as well as induced apoptosis of NSCLC cells. The anticancer effect of phycocyanin was also validated in vivo using subcutaneous tumor formation model in nude mice. This study proposes that phycocyanin inhibits NSCLC cell activities through miR-642a-5p/RIPK1/NF-κB axis.

Remimazolan inhibits glioma cell growth and induces apoptosis through down-regulation of NF-κB pathway.

Glioma alone accounts for 30% of various kinds of primary brain tumors and is the highest cause of mortality associated with intracranial malignant cancers. In the present study, Suzuki-coupling products of remimazolan were synthesized and investigated for anti-neoplastic property against glioma cells. RFMSP treatment for 48 hr suppressed viabilities of U-118MG and U87MG cells in dose dependent manner. Exposure of primary astrocytes to RFMSP at 2-20 μM concentration range minimally affected viabilities. RFMSP treatment at 5 μM doses raised apoptotic cell count to 53.8 ± 2.3% and 48.2 ± 1.8%, respectively in U-118MG and U87MG cells. Treatment of the cells with RFMSP induced nuclear condensation and subsequent fragmentation. In RFMSP treated U-118MG and U87MG cells, NF-κB p65 expression was markedly suppressed compared to the control cells. Additionally, RFMSP treatment decreased the ratio of nuclear to total NF-κB p65 level in both the cell lines. Treatment of U-118MG and U87MG cells with 5 μM RFMSP for 48 hr caused a marked down-regulation in survivin and XIAP levels. Treatment with RFMSP promoted Bax expression and suppressed Bcl-2 level. The caspase-9 and -3 activation was markedly induced by RFMSP treatment in U-118MG and U87MG cells compared to the control cells. In summary, the RFMSP synthesized by Suzuki-coupling of RFMSP inhibited glioma cell survival via DNA damage mediated apoptosis. The anti-glioma potential of RFMSP involved down-regulation of NF-κB expression, targeted survivin & XIAP levels and induced caspase activation in glioma cells. Therefore, RFMSP may be studied further as therapeutic agent for the treatment of glioma.

Antineoplastic property of Ashwagandha for Paclitaxel concomitant, can induce p53-mediated apoptosis: In vitro search for anti-proliferative phytogent

Ashwagandha (Withania somnifera L. Dunal) is an important and traditional medicinal herb found in India. It has been reported that, Ashwagandha has potential anti-proliferative as well as chemo-accelerative activity. The goal of this study was to investigate the most probable reason behind Ashwagandha’s anti-proliferative and chemo-accelerative activity. In addition, chromatographically isolate and chemically characterize some new compound which have antineoplastic property and find the mode of action of it. In vitro assays (MTT and Western blot) for anti-tumorigenic potentiality of the isolated drug were carried out on HT-29, KB and HeLa cell lines. In this experimental study, purification and chemical characterization (by UV, FT-IR, HPLC, LC-MS, 1H-NMR) of an anti-cancer drug has been found as Paclitaxel. MTT-assay shows an average IC50 value of the isolated Paclitaxel is 10 nM. Western blot data reveals there may be ROS-associated p53-MDM2-related cell proliferation and apoptosis by the drug’s in vitro effect.

Antineoplastic property of Ashwagandha for Paclitaxel concomitant, can induce p53-mediated apoptosis: In vitro search for anti-proliferative phytogent

Antineoplastic property of Ashwagandha for Paclitaxel concomitant, can induce p53-mediated apoptosis: In vitro search for anti-proliferative phytogent

Integrating LINCS Data to Evaluate Cancer Transcriptome Modifying Potential of Small-molecule Compounds for Drug Repositioning.

Conventional high-throughput chemical screens in conjunction with genome-wide gene expression profiling proves to be successful in novel anti-cancer agent discovery and provides comprehensive insights into the mechanisms of action and off-target effects of single small-molecule compound. However, systematic evaluation on heterogeneous transcriptional responses of different cancer cell types to thousands of independent perturbations in a bioinformatics way is still limited. Here, we introduce cancer transcriptome modifying potential (CTMP) which uses "Connectivity Score" to quantify and compare the effects of approved antineoplastic drugs on transcriptionally restoring dysregulated (both up- and down-) gene expressions at cancer state towards normal state. As a proof-of-concept, we applied this CTMP computational evaluation on > 10,000 small-molecule compounds using >200,000 Library of Integrated Network-based Cellular Signatures (LINCS) expression profiles generated upon 4 different cancer cell lines. We screened and proposed a candidate list of cancer transcriptome modifying therapeutics (CTMTs), among which the approved on-market drugs are further validated using GDSC drug sensitivity data, highlighting their potential to facilitate direct antineoplastic repositioning. In total, we calculated CTMPs of 85 on-market antineoplastic drugs and ~15,000 smallmolecule compounds using 253,813 transcriptomes across four cancer cell lines of lung, melanoma, prostate, and colon. Our results reveal that regardless of the chemical structure and targeted proteins majority of approved antineoplastic drugs present significant bilateral CTMPs across all 4 cancer cell lines. Bilateral CTMP-based systematic screen further indicates that candidate CTMTs are limited and most notably cancer-type specific. In particular, for each cancer cell type we proposed 3~5 CTMTs that are approved drugs with potent sensitivity data to support development in antineoplastic indications. Our work establishes CTMP to evaluate the antineoplastic property of small-molecule compounds and suggests CTMP-based systematic screen of cancer type-specific CTMTs as a feasible strategy in drug repositioning for precise anti-cancer purposes.

Porous Tantalum and Titanium in Orthopedics: A Review.

Porous metal is metal with special porous structures, which can offer high biocompatibility and low Young's modulus to satisfy the need for orthopedic applications. Titanium and tantalum are the most widely used porous metals in orthopedics due to their excellent biomechanical properties and biocompatibility. Porous titanium and tantalum have been studied and applied for a long history until now. Here in this review, various manufacturing methods of titanium and tantalum porous metals are introduced. Application of these porous metals in different parts of the body are summarized, and strengths and weaknesses of these porous metal implants in clinical practice are discussed frankly for future improvement from the viewpoint of orthopedic surgeons. Then according to the requirements from clinics, progress in research for clinical use is illustrated in four aspects. Various creative designs of microporous and functionally gradient structure, surface modification, and functional compound systems of porous metal are exhibited as reference for future research. Finally, the directions of orthopedic porous metal development were proposed from the clinical view based on the rapid progress of additive manufacturing. Controllable design of both macroscopic anatomical bionic shape and microscopic functional bionic gradient porous metal, which could meet the rigorous mechanical demand of bone reconstruction, should be developed as the focus. The modification of a porous metal surface and construction of a functional porous metal compound system, empowering stronger cell proliferation and antimicrobial and antineoplastic property to the porous metal implant, also should be taken into consideration.

Differential Effects of In Vitro Treatment with Cinobufotalin on Three Types of Ovarian Cancer Cells.

Cinobufotalin (CINO), a cardiotonic steroid, has been used as an anticancer agent. This study assessed the cell-specific effect of CINO on SK-OV-3, CRL-1978 and CRL-11731 ovarian cancer cells which differ in terms of their respective karyotypes. Cell cultures were treated with CINO (0.1, 1, 5 and 10 μM) for 24, 48, and 72 h. Cell proliferation, migration, and invasion were measured using CellTiter, Cytoselect, and FluoroBlock assays, respectively. Expression of proliferating cell nuclear antigen (PCNA) was evaluated by western blot analysis. Cell viability was determined by fluorescence-activated cell sorting. Immunofluorescence was performed using Annexin-V staining and fluorescein isothiocyanate (FITC). Mitochondrial membrane potential (MMP) was measured using MitoTracker™ Red. CINO at 0.5 μM inhibited SK-OV-3, CRL-1978, and CRL-11731 proliferation, migration, and invasion. Each cell type differed in response to CINO doses for PCNA, Annexin-V expression and MMP. The antineoplastic property of CINO is consistent, but its mode of action varies among cell lines.

Phycocyanin Reduces Proliferation of Melanoma Cells through Downregulating GRB2/ERK Signaling.

As a type of functional food additive, phycocyanin is shown to have a potential antineoplastic property. However, its underlying anticancer mechanism in melanoma cells remains unknown. We previously reported a 35S in vivo/vitro labeling analysis for dynamic proteomic (SiLAD) technology. It could exclusively detect protein synthesis rates via pulse labeling of newly expressed proteins by 35S, providing a high time-resolution method for analysis of protein variations. In the present study, we performed a time course analysis in A375 melanoma cells after phycocyanin treatment using SiLAD. Protein expression velocities were specifically visualized and their regulation modes were dynamically traced. Strikingly, novel protein synthesis patterns were discovered in the early phase of phycocyanin treatment, suggesting a possible mechanism of phycocyanin regulation. Furthermore, network analysis and phenotype experiments demonstrated that GRB2-ERK1/2 pathway was involved in phycocyanin-mediated regulation process and responsible for the proliferation suppression of melanoma cell, which could be a therapeutic target for malignant melanoma.

Insight into the roles of vitamins C and D against cancer: Myth or truth?

The consumption of vitamins C and D for prevention and treatment of cancer is still an uncertain recommendation due to their controversial roles in cancer. The epidemiological studies document that vitamins C and D possess potential antineoplastic property. In addition, accumulating experimental studies strongly support their anticancer efficacy both in vitro and in vivo, although the mechanisms of action are not completely clear. Vitamin C at pharmacological concentration has cancer-selective cytotoxicity in several cancer cell lines. Moreover, the cognition of vitamin D has become “hormone D”, which modulates a variety of molecular targets and signaling pathways, contributing to the inhibition of cancer. Furthermore, limited small-scale clinical trials favor their roles as the adjuncts of standard cancer therapies. On the other hand, opposite opinions also exist, and high-quality evidence are still lacking to ascertain the roles of vitamins C and D in cancer. In general, in light of the potential and promising anticancer values of vitamins C and D, it is essential to gain insight into their roles in cancer based on current epidemiological, experimental and clinical studies.

Antioxidant, cytotoxic and antineoplastic effects of Carissa carandas Linn. leaves

For scientific clarification of some traditional uses, this study was designed to explore the antioxidant, cytotoxic and antineoplastic properties of leaf extract of Carissa carandas Linn., a traditional medicinal plant of Bangladesh. The methanol extract of Carissa carandas leaves (MELC) was applied on DPPH and ABTS experiments to determine its antioxidant activity. In vitro the cytotoxic effect of MELC was evaluated against colonic adenocarcinoma cell lines (SW-480 and SW-48) whereas in vivo its antineoplastic property was tested against Ehrlich ascites carcinoma (EAC). The DPPH and ABTS assays revealed the antioxidant activity of MELC with IC50 10.5±1.2 and 1.75±0.3μg/ml that was comparable to L-ascorbic acid. In vitro cytotoxic study, MELC reduced the viability of adenocarcinoma cells in dose dependent manner and in vivo, administration of MELC (25mg/kg) resulted in a significant (p<0.05) decrease in viable EAC cell count thereby increasing the life span of the EAC cell bearing mice. Restoration of hematological parameters such as red blood cells (RBC), hemoglobin and white blood cells (WBC) to normal levels in MELC-treated mice was also observed. Moreover, treatment with MELC induced apoptosis of EAC cells as observed in fluorescence microscopic view of DAPI (4,6-diamidino-2-phenylindole) stained cells and also increased p53 gene expression MELC-treated cells in respect to untreated EAC control. In addition, the MELC was rich in polyphenol content and its GC–MS chromatogram confirmed the presence of some compounds all of which showed anticancer and cytotoxic activities in previous studies. In a word, this study supports the use of Carissa carandas in traditional medicine as well as highlights the need to further explore the potentials of MELC as an antineoplastic agent.

Anti-EGFR-iRGD recombinant protein conjugated silk fibroin nanoparticles for enhanced tumor targeting and antitumor efficiency.

In this study, we report a novel kind of targeting with paclitaxel (PTX)-loaded silk fibroin nanoparticles conjugated with iRGD–EGFR nanobody recombinant protein (anti-EGFR-iRGD). The new nanoparticles (called A-PTX-SF-NPs) were prepared using the carbodiimide-mediated coupling procedure and their characteristics were evaluated. The cellular cytotoxicity and cellular uptake of A-PTX-SF-NPs were also investigated. The results in vivo suggested that NPs conjugated with the recombinant protein exhibited more targeting and anti-neoplastic property in cells with high EGFR expression. In the in vivo antitumor efficacy assay, the A-PTX-SF-NPs group showed slower tumor growth and smaller tumor volumes than PTX-SF-NPs in a HeLa xenograft mouse model. A real-time near-infrared fluorescence imaging study showed that A-PTX-SF-NPs could target the tumor more effectively. These results suggest that the anticancer activity and tumor targeting of A-PTX-SF-NPs were superior to those of PTX-SF-NPs and may have the potential to be used for targeted delivery for tumor therapies.

Copper Enhances Antitumor Activity of Water Soluble Garlic Extract Components on a Human Hepatoma Cell Line

Water garlic extract combined with Copper (GE-Cu) shows specific anti-proliferative and antitumoral activity in human hepatocarcinoma (HepG2) cancer cell line, while it is not active on differentiated or primary isolated cells, normal human dermal fibroblasts (HDF) and human epidermal keratinocytes (HEK). Since other transition metals do not affect cell viability, the observed antineoplastic property, was found specific for copper (Cu), and atomic absorption analyses demonstrate an accumulation of this metal inside the cell nuclei. GE-Cu treatment of HepG2a cancer cells, induces cell differentiation, growth arrest and programmed cell death. Furthermore, GE-Cu produces a continuous and prolonged flux of oxidative radicals, which down-regulates nuclear antioxidant defenses and repair systems, thus generating direct double-strand breaks to DNA. Indeed, it was observed that in GE-Cu-treated HepG2 cancer cells, histone deacetylase (HDAC) is inhibited, and histone H2AX is early phospho-activated. DNA double strand break downstream, likely responsible for the observed cell death in HepG2 cell, was evidenced by an early over expression of p53 and p21. JNK/c-Jun and p-38 phosphorylative cascade are activated as response to oxidative stress also. The resulting apoptosis appears to be caspases-independent because, under our experimental conditions, nuclear translocation of the apoptosis inducing factor (AIF) is operative. Our data suggest that GE-Cu possess an active specific antitumor capability, which could provide valuable new tools in cancer prevention and in supporting traditional chemotherapy.

Myrtenal ameliorates diethylnitrosamine‐induced hepatocarcinogenesis through the activation of tumor suppressor protein p53 and regulation of lysosomal and mitochondrial enzymes

Myrtenal is a novel class of compound belongs to monoterpenes found predominantly in mint, pepper, etc., and it was shown to have excellent pharmacological activities against many diseases among which cancer is imperative. Hepatocellular carcinoma is a primary malignancy of the hepatocytes, which rapidly leads to death in short periods. The aim of this study was to investigate the possible therapeutic efficiency of myrtenal against diethylnitrosamine-induced experimental hepatocarcinogenesis by analyzing the key enzymes of carbohydrate metabolism, lysosomal and mitochondrial TCA cycle enzymes, and also the possible role of tumor suppressor protein p53, and scanning electron microscopic studies. The results revealed that myrtenal significantly ameliorated the altered enzymes of carbohydrate metabolism, lysosomal and mitochondrial enzymes, and interestingly the tumor suppressor protein p53 was found to be significantly accumulated in myrtenal-treated animals, which inevitably confirms that myrtenal has a prominent role in preventing the liver cancer during treatment. Furthermore, the antineoplastic property was well evidenced by the mRNA expression of p53 protein by the reverse-transcriptase polymerase chain reaction and immunoblot analysis. The observed anticancer property of myrtenal may be due to the involvement and expression of p53 and influence in the mitochondrial and lysosomal membrane integrity and also interference in the gluconeogenesis process of cancer cells. Our results suggest that myrtenal is very efficient and useful compound in the treatment of liver cancer in future.

Predicting Skin Permeability of Chemical Substances using a Quantitative Structure-activity Relationship

Abstract The health hazard arising from skin exposure to toxic chemical was conventionally evaluated by determining the skin permeation coefficient ( Kp ) of chemical in the stratum corneum of human or animal cadaver skin. However, limited by constraints inherent in the technique, to date the Kp evaluation has been performed only insufficiently. This study defined a quantitative structure-activity relationship (QSAR) for Kp prediction and for characterization of, at a molecular level, the physicochemical properties involved in transdermal transport of chemical. One hundred and fifty-eight chemical substances of known Kp determined in vitro using human skin were selected in the QSAR development. The final QSAR consisted of four molecular descriptors, including those describing electrostatic interactions between electric quadrupoles of van der Waals forces, octanol-water partitioning of solute, similarity in antineoplastic property, and frequency of carbon-nitrogen bonding at a constant topological distance. The four-descriptor multiple linear regression model fit the observed Kp data with a R 2 of 0.828 and a mean percentage error of 18.8%, suggesting a capacity of this QSAR to serve as an alterative source of Kp information and a potential tool of dermal hazard characterization, particularly when experimentally determined Kp are not readily available.

Anti-tumor effect by inhibition of NF-κB activation using nafamostat mesilate for pancreatic cancer in a mouse model

Constitutive NF-kappaB activation plays a key role in the aggressive behavior of pancreatic cancer. We have reported that nafamostat mesilate, a serine-protease inhibitor, inhibited NF-kappaB activation and induced apoptosis in human pancreatic cancer cells. The aim of this study is to evaluate the therapeutic efficacy of nafamostat mesilate against pancreatic cancer. In vitro, nafamostat mesilate inhibited NF-kappaB activation of human pancreatic cancer cell line (Panc-1) by suppressing IkappaBalpha phosphorylation and induced caspase-8 mediated apoptosis. In vivo, Panc-1 was implanted into the back of nude mice. Five weeks after implantation, nafamostat mesilate was injected intraperitoneally as the treatment group (n=11) three times a week for six weeks, while the control group (n=13) received vehicle only. At the end of six-week treatment, the tumors grew up to 12.89+/-4.27 mm (mean +/- SD) in the treatment group, and 17.93+/-4.45 mm in the control group, respectively. The tumor volume and weight of the treatment group were reduced by 43 and 61% as compared with the control group. The tumor growth was significantly inhibited in the treatment group (p<0.0001). Assays of primary tumors also indicated that nafamostat mesilate inhibited NF-kappaB activation by suppressing IkappaBalpha phosphorylation, resulting in caspase-8 mediated apoptosis. These results suggested that nafamostat mesilate has anti-neoplastic property against experimental pancreatic cancer.

Anti-tumor effect by inhibition of NF-κB activation using nafamostat mesilate for pancreatic cancer in a mouse model

Constitutive NF-κB activation plays a key role in the aggressive behavior of pancreatic cancer. We have reported that nafamostat mesilate, a serine-protease inhibitor, inhibited NF-κB activation and induced apoptosis in human pancreatic cancer cells. The aim of this study is to evaluate the therapeutic efficacy of nafamostat mesilate against pancreatic cancer. In vitro, nafamostat mesilate inhibited NF-κB activation of human pancreatic cancer cell line (Panc-1) by suppressing IκBα phosphorylation and induced caspase-8 mediated apoptosis. In vivo, Panc-1 was implanted into the back of nude mice. Five weeks after implantation, nafamostat mesilate was injected intraperitoneally as the treatment group (n=11) three times a week for six weeks, while the control group (n=13) received vehicle only. At the end of six-week treatment, the tumors grew up to 12.89±4.27 mm (mean ± SD) in the treatment group, and 17.93±4.45 mm in the control group, respectively. The tumor volume and weight of the treatment group were reduced by 43 and 61% as compared with the control group. The tumor growth was significantly inhibited in the treatment group (p<0.0001). Assays of primary tumors also indicated that nafamostat mesilate inhibited NF-κB activation by suppressing IκBα phosphorylation, resulting in caspase-8 mediated apoptosis. These results suggested that nafamostat mesilate has anti-neoplastic property against experimental pancreatic cancer.

Efficacy of Curcuma longa Extract Against DMBA Induced Skin Cancer in Rats

Bhutia, Y.D., Saini, M., Sharma, A.K., Sharma, B. and Swarup, D. 2009. Efficacy of Curcuma longa extract against DMBA induced skin cancer in rats. J. Appl. Anim. Res., 36: 291–296. The study was aimed to evaluate the antineoplastic property of 70% ethanolic extract of Curcuma longa extract both in vitro and in vivo. In vitro study was conducted using B16F10 melanoma cell line and the cytotoxic activity of the extract was evaluated using Trypan Blue Dye Exclusion test, MTT assay and apoptosis. In vivo study comprised of safety testing and evaluating the chemopreventive effect of the extract on 7, 12- dimethyl-benz[a]anthracene (DMBA)-induced skin cancer in Wistar rats. The extract revealed in vitro cytotoxic activity and caused apoptosis in nearly 80% of the cells as studied by FACS. 100, 200 and 400 mg/kg C. longa administered orally 15 d before initiation and continued till the end of experiment caused significant delay in the onset and reduction in overall incidence and average number of lesions in rats. There were mostly papilloma and squamous cell carcinoma in positive control but only mild papillomatous lesions without any evidence of infiltration in C. longa treated groups. The tumor remained suppressed as long as the extract was fed but its withdrawal led to recurrence. These findings are suggestive of the continued ingestion of C. longa to benefit from its anticarcinogenic potential.