Drugs For Treatment Of Cancer Research Articles

Navigating Molecular Pathways: An Update on Drugs in Colorectal Cancer Treatment.

Colorectal cancer (CRC) is a multifaceted and heterogeneous ailment that affects the colon or rectum of the digestive system. It is the second most commonly occurring form of cancer and ranks third in terms of mortality rate. The progression of CRC does not occur due to a single mutational event; rather, it is the result of the sequential and cumulative accumulation of mutations in key driver genes of signaling pathways. The most significant signaling pathways, which have oncogenic potential due to their deregulation, include Wnt/β-catenin, Notch, TGF-β, EGFR/MAPK, and PI3K/AKT pathways. Numerous drug target therapies have been developed to treat CRC using small molecule inhibitors, antibodies, or peptides. Although drug-targeted therapy is effective in most cases, the development of resistance mechanisms in CRC has raised questions about their efficacy. To overcome this issue, a novel approach to drug repurposing has come to light, which utilizes already FDA-approved drugs to treat CRC. This approach has shown some promising experimental results, making it a crucial avenue of research in the treatment of CRC.

Comparison Of 3D Structures Generated by AlphaFold2 to Experimental Structures In Oncogenic Proteins

AlphaFold2 is a machine-learning algorithm that can predict the 3D structure of proteins. 3D protein structures are essential for understanding the function of oncogenic proteins, which can potentially cause cancer. In this study, we compared the structure of 26 oncogenic proteins found experimentally and computationally using AlphaFold2. We used RMSD values to measure how well the AlphaFold2 model fit the experimentally derived protein structures. RMSD values for the oncogenic proteins ranged from 0.204 Å to 1.980 Å with an average of 0.633 Å, showing that AlphaFold2 was a promising tool for predicting the 3D structure of oncogenic proteins. However, we noted that AlphaFold2 has limitations in predicting the structure of highly disordered proteins, proteins with multiple conformations, mutated and artificial proteins, and proteins that are not well-studied experimentally. Our study suggests that AlphaFold2 could be used to identify new targets for cancer treatment and design drugs that can fit into the binding sites of oncogenic proteins. We also hypothesize that AlphaFold2 could be improved by increasing the amount of data available for training, improving the resolution of current data, and using it in conjunction with other protein structure models. We believe that AlphaFold2 is a powerful tool for predicting the structure of oncogenic proteins. Despite the current limitations, we are optimistic that future research will improve AlphaFold2, finding use in cancer research.

Measuring Drug Response with Single-Cell Growth Rate Quantification.

Intratumoral heterogeneity is a substantial cause of drug resistance development during chemotherapy or other drug treatments for cancer. Therefore, monitoring and measuring cell exposure and response to drugs at the single-cell level are crucial. Previous research suggested that the single-cell growth rate can be used to investigate drug-cell interactions. However, currently established methods for quantifying single-cell growth are limited to isolated or monolayer cells. Here, we introduce a technique that accurately measures both 2D and 3D cell growth rates using label-free ratiometric stimulated Raman scattering (SRS) microscopy. We use deuterated amino acids, leucine, isoleucine, and valine, as tracers and measure the C-D SRS signal from deuterium-labeled proteins and the C-H SRS signal from unlabeled proteins simultaneously to determine the cell growth rate at the single-cell level. The technique offers single-cell level drug sensitivity measurement with a shorter turnaround time (within 12 h) than most traditional assays. The submicrometer resolution of the imaging technique allows us to examine the effects of chemotherapeutic drugs, including kinase inhibitors, mitotic inhibitors, and topoisomerase II inhibitors, on both the cell growth rate and morphology. The capability of quantifying 3D cell growth rates provides insight into a deeper understanding of the cell-drug interaction in the actual tumor environment.

Hybrid nanocarriers based on polyacrylic acid, polyvinyl pyrrolidone, and molybdenum disulfide for enhanced 5-fluorouracil delivery in lung cancer therapy

An innovative hydrogel nanocomposite, synthesized from a hybrid of PAA, PVP, and MoS2, represents a pioneering solution for pH-responsive drug delivery. This nanocomposite is specifically tailored for the controlled release of 5-Fluorouracil (5-FU), an anti-cancer agent. The infusion of MoS2 into the PAA-modified PVP hydrogel imparts a distinct feature, further enriched by the incorporation of Span 80 surfactant, culminating in the creation of stable niosomal microemulsions that enhance the retention of 5-FU. The incorporation of paraffin oil helps reduce the size of the microemulsions while maintaining their quasi-spherical shape. To characterize the microemulsions in this study, we employed FT-IR spectroscopy and X-ray diffraction (XRD) methods for our analysis. Additionally, Dynamic Light Scattering (DLS) analysis confirmed the presence of nanoparticles within the nanocarriers, with an average dimension of nearly 315 nm and a polydispersity index (PDI) of 0.27. These entities exhibit a spherical morphology, as revealed by SEM imaging. Zeta potential measurements highlight a negative surface charge of approximately –33.5 mV. Remarkably, we achieved significant drug loading and entrapment efficiencies, reaching 46 % and 87.25 %, respectively, surpassing those reported for other nanocarriers in previous studies. Cellular experiments conducted on A549 and L929 cell lines showcased the enhanced anticancer activity of 5-FU-loaded nanoparticles and assessed potential side effects.The results underscore the promising potential of the nanocarrier as a favorable strategy for delivering drugs in cancer treatment.

Quinoline-based thiazolyl-hydrazones target cancer cells through autophagy inhibition.

Heterocyclic pharmacophores such as thiazole and quinoline rings have a significant role in medicinal chemistry. They are considered privileged structures since they constitute several Food and Drug Administration (FDA)-approved drugs for cancer treatment. Herein, we report the synthesis, in silico evaluation of the ADMET profiles, and in vitro investigation of the anticancer activity of a series of novel thiazolyl-hydrazones based on the 8-quinoline (1a-c), 2-quinoline (2a-c), and 8-hydroxy-2-quinolyl moiety (3a-c). The panel of several human cancer cell lines and the nontumorigenic human embryonic kidney cell line HEK-293 were used to evaluate the compound-mediated in vitro anticancer activities, leading to [2-(2-(quinolyl-8-ol-2-ylmethylene)hydrazinyl)]-4-(4-methoxyphenyl)-1,3-thiazole (3c) as the most promising compound. The study revealed that 3c blocks the cell-cycle progression of a human colon cancer cell line (HCT-116) in the S phase and induces DNA double-strand breaks. Also, our findings demonstrate that 3c accumulates in lysosomes, ultimately leading to the cell death of the hepatocellular carcinoma cell line (Hep-G2) and HCT-116 cells, by the mechanism of autophagy inhibition.

Cytotoxic Activities of Isolated Compounds from Prangos uechtritzii Boiss & Hausskn

Prangos uechtritzii Boiss&Hausskn is an endemic plant of Türkiye, and the plant roots are rich in coumarins. This study aims to evaluate the cytotoxic activities of the 16 natural compounds along with the n-hexane (PH), chloroform (PC), and methanol (PM) extracts of P. uechtritzii. For this purpose, fourteen coumarin derivatives; umbelliferone(1), 6-formylumbelliferone(2), suberosin(3), 7-demethylsuberosin(4), (+)-ulopterol(5), tamarin(6), psoralen(7), imperatorin(8), (+)-oxypeucedanin(9), (+)-oxypeucedanin hydrate(10), (+)-oxypeucedanin methanolate(11), (+)-marmesin(12), (-)-prantschimgin(13), and (-)-adicardin(14); two polyacetylenes (-)-panaxynol(15), (+)-falcarindiol(16) and three extracts (PH, PC, and PM) were tested for their cytotoxicity against two healthy (HK-2, NIH/3T3), and four cancer (MCF-7, A-549, SH-SY5Y, PC-3) cells by WST-1 method. Doxorubicin was used as a positive control. PH and PC showed cytotoxic effects on all the cell lines with IC50 values of 8.16-91.56 μg/mL. PH displayed a selective effect on SH-SY5Y cells [Selectivity Index (SI)= 2.5] compared to NIH/3T3. PC exhibited cytotoxic effects on PC-3 cells (SI=2) compared to both NIH/3T3, and HK-2. PM didn’t display cytotoxicity at 100 μg/mL. (-)-Panaxynol, (+)-falcarindiol, 6-formylumbelliferone, 7-demethylsuberosin, and suberosin exhibited effects with IC50 values of 8.65-87.91 μM, while others didn’t work at 100 μM. So, P. uechtritzii could be a promising natural source in the development of new drugs for cancer treatment.

Interaction of PUFAs and Doxorubicin: the Enhanced Toxicity in Breast Cancer Cells

Doxorubicin (DOX) still remains one the most effective a clinical drug for breast cancer treatment. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the n-3 polyunsaturated fatty acids (PUFAs), exert pronounced toxicity against many types of cancers including breast cancer. That is why it was decided to investigate the mechanism of DOX and PUFAs toxicity on SK-BR-3 and MDA-MB-231 cells. The influence of DOX on the PUFAs oxidation and effect of DOX and EPA or DHA on cellular metabolic activity, viability, cytotoxicity, apoptosis and oxidative DNA damage in these cells were measured. DOX induced oxidation of the EPA and DHA. Toxicity of DOX and PUFAs towards breast cancer cells was associated with oxidative damage. These PUFAs reduced growth of the tested cells and caused their death. EPA and DHA potentiated DOX toxic effects through induction of oxidative DNA damage. The antitumor effect of PUFAs alone and combined with DOX strongly depended on induction of the oxidative stress that facilitated cell death. The observed changes of DOX toxicity induced by PUFAs suggest the possibility of their application in developing therapeutic anticancer strategies.

Fluorinated borono-phenylalanine for optimizing BNCT: Enhancing boron absorption against hydrogen scattering for thermal neutrons.

Boron-containing compounds, such as 4-borono-phenylalanine (BPA) are used as drugs for cancer treatment in the framework of Boron Neutron Capture Therapy (BNCT). Neutron irradiation of boron-rich compounds delivered to cancer cells triggers nuclear reactions that destroy cancercells. We provide a modeling of the thermal neutron cross sectionof BPA, a drug used in Boron Neutron Capture Therapy (BNCT), to quantify the competing contributions of boron absorption against hydrogen scattering, for optimizing BNCT by minimizing thelatter. We perform the experimental determination of the total neutron scattering cross sectionof BPA at thermal and epithermal neutron energies using neutron transmission measurements. We isolate the contribution related to the incoherent scattering by hydrogen atoms as a function of the neutron energy by means of the Average Functional Group Approximation, and we calculate the probability for a neutron of being absorbed as a function of the neutron energy both for BPA and for its variants where either one or all four aromatic hydrogen atoms are substituted by 19 F, and both for the samples with natural occurrence or enriched concentration of 10 B. While referring to the already available literature for in vivo use of fluorinated BPA, we show that fluorine-rich variants of BPA increase the probability of neutrons being captured by the molecule. As the higher absorption efficiency of fluorinated BPA does not depend on whether the molecule is used in vivo or not, our results are promising for the higher efficiency of the boron neutron capturetreatment. Our results suggest a new advantage using fluorinated compounds for BNCT, in their optimized interaction with neutrons, in addition to their already known capability to be used for monitoring and pharmacokinetics studies using 19 F-Nuclear Magnetic Resonance or in 18 F-Positron EmissionTomography.

NcRNADrug: a database for validated and predicted ncRNAs associated with drug resistance and targeted by drugs.

Drug resistance is a major barrier in cancer treatment and anticancer drug development. Growing evidence indicates that non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), play pivotal roles in cancer progression, therapy, and drug resistance. Furthermore, ncRNAs have been proven to be promising novel therapeutic targets for cancer treatment. Reversing dysregulated ncRNAs by drugs holds significant potential as an effective therapeutic strategy for overcoming drug resistance. Therefore, we developed ncRNADrug, an integrated and comprehensive resource that records manually curated and computationally predicted ncRNAs associated with drug resistance, ncRNAs targeted by drugs, as well as potential drug combinations for the treatment of resistant cancer. Currently, ncRNADrug collects 29551 experimentally validated entries involving 9195 ncRNAs (2248 miRNAs, 4145 lncRNAs and 2802 circRNAs) associated with the drug resistance of 266 drugs, and 32969 entries involving 10480 ncRNAs (4338 miRNAs, 6087 lncRNAs and 55 circRNAs) targeted by 965 drugs. In addition, ncRNADrug also contains associations between ncRNAs and drugs predicted from ncRNA expression profiles by differential expression analysis. Altogether, ncRNADrug surpasses the existing related databases in both data volume and functionality. It will be a useful resource for drug development and cancer treatment. ncRNADrug is available at http://www.jianglab.cn/ncRNADrug.

Spectroscopic Characterization, Quantum Chemical, Molecular Docking, Antibacterial and Anticancer Studies on Ethyl Coumarin-3-Carboxylate: an Antibacterial and Lung Cancer Agent

The detailed theoretical and experimental (FT-IR, FT-Raman, UV-visible) spectroscopy analyses of the Ethyl Coumarin-3-Carboxylate (ECC) molecule were carried out. The ECC compound’s pharmacological properties were also investigated, utilizing antibacterial and anticancer activity investigations. Initially, the ECC molecule was optimized by the density functional theory B3LYP method with a 6-311 G++ (d,p) basis set using the Gaussian 09 W program. The optimized molecular structure provides the harmonic vibrational frequencies of the ECC molecule. The observed and computed vibrational wavenumbers were assigned and found to be well correlated. UV-Vis absorption spectrum analysis indicates that the molecule contains π →π* and n → π* electronic transitions. The Frontier molecular orbital analysis confirmed the molecular reactivity and bioactivity of ECC, while the Mulliken atomic charge distribution analysis pinpointed the molecule’s reactive sites. Antibacterial testing demonstrated the ECC compound’s inhibitory effect on various bacterial strains, with a particular impact on Klebsiella pneumonia. In vitro, anticancer assessments showcased ECC's stronger inhibitory effects on A549 lung cancer cell lines compared to HeLa cervical cancer cell lines. Additionally, in silico molecular docking investigations provided further validation that the ECC compound can inhibit the function of the epidermal growth factor receptor, a factor associated with lung cancer. As a result, this study lays the foundation for the development of novel drugs for lung cancer treatment.

Polyamidoamine dendrimer-mediated hydrogel for solubility enhancement and anti-cancer drug delivery.

The application of hydrogels for anti-cancer drug delivery has garnered considerable interest in the medical field. Current cancer treatment approaches, such as chemotherapy and radiation therapy, often induce severe side effects, causing significant distress and substantial health complications to patients. Hydrogels present an appealing solution as they can be precisely injected into specific sites within the body, facilitating the sustainable release of encapsulated drugs. This localized treatment approach holds great potential for reducing toxicity levels and improving drug delivery efficacy. In this study we developed a hydrogel delivery system containing polyamidoamine (PAMAM) dendrimer and polyethylene glycol (PEG) for solubility enhancement and sustained delivery of hydrophobic anti-cancer drugs. The three selected model drugs, e.g. silibinin, camptothecin, and methotrexate, possess limited aqueous solubility and thus face restricted application. In the presence of vinyl sulfone functionalized PAMAM dendrimer at 45 mg/mL concentration, drug solubility is increased by 37-fold, 4-fold, and 10-fold for silibinin, camptothecin, and methotrexate, respectively. By further crosslinking of the functionalized PAMAM dendrimer and thiolated PEG, we successfully developed a fast-crosslinking hydrogel capable of encapsulating a significant payload of solubilized cancer drugs for sustained release. In water, the drug encapsulated hydrogels release 30%-80% of their loads in 1-4days. MTT assays of J82 and MCF7 cells with various doses of drug encapsulated hydrogels reveal that cytotoxicity is observed for all three drugs on both J82 and MCF7 cell lines after 48h. Notably, camptothecin exhibits higher cytotoxicity to both cell lines than silibinin and methotrexate, achieving up to 95% cell death at experimental conditions, despite its lower solubility. Our experiments provide evidence that the PAMAM dendrimer-mediated hydrogel system significantly improves the solubility of hydrophobic drugs and facilitates their sustained release. These findings position the system as a promising platform for controlled delivery of hydrophobic drugs for intratumoral cancer treatment.

Theranostic siRNA loaded mesoporous silica nanoplatforms: A game changer in gene therapy for cancer treatment

Growing interest has been seen in non-pathogenic, safe, and effective gene therapy delivery systems. There are many nucleic acid therapies that have been studied to alter the expression of DNA or RNA, such as mRNA, siRNA, antisense DNA, and microRNA (miRNA), of which siRNA has been shown to be useful in blocking specific genes. The development of an efficient nucleic acid delivery method is crucial for molecular diagnostic and therapeutic systems. Mesoporous silica nanoparticles (MSNs) with high porosity, good textural qualities, and biocompatibility have been studied for use in drug delivery systems. They are being utilized more and more in combination therapy, gene silencing, and other biological applications, especially in cancer nanomedicine. MSNs offer efficient drug loading and controlled release, and additions can change their characteristics. They are widely employed in target medication delivery, biosensing, cellular uptake, and diagnostics in the biomedical field. Additionally, they have been connected to theranostic drugs for cancer treatment. This review highlights the current state of knowledge of MSNs and their specialized applications as theranostic agents for cancer management.

Effects of the Supercritical Fluid Extract of Magnolia figo on Inducing the Apoptosis of Human Non-Small-Cell Lung Cancer Cells

Lung cancer has a high incidence rate worldwide, necessitating the development of new drugs. Although Magnolia figo (Lour.) DC. is known for its medicinal properties, studies on its efficacy against lung cancer are lacking. This study investigated whether the supercritical fluid extract of M. figo (FMO) can induce apoptosis in A549, a human non-small-cell lung cancer cell line. The cell viability was assessed using an MTT assay. A terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis and flow cytometry analysis were conducted. The expression of factors was assessed through Western blotting analyses. Gas chromatography–mass spectrometry (GC-MS) was performed. The results revealed that FMO treatment exhibited cytotoxicity, demonstrating dose-dependent effects. The TUNEL analysis and flow cytometry analysis revealed that FMO induced apoptosis in A549 cells. The Western blotting analysis revealed that FMO upregulated the expression of p53 and Bax protein, and downregulated the expression of Bcl-2 protein. The GC-MS analysis revealed eight components identified in FMO. These findings indicate that FMO can induce A549 apoptosis through the p53/Bcl-2/Bax pathways, confirming the apoptotic effects of M. figo on lung cancer cells. These results highlight the potential, for the first time, of M. figo as a source for developing novel drugs for lung cancer treatment.

Antitumor activity of bengamide ii in a panel of human and murine tumor cell lines: In vitro and in vivo determination of effectiveness against lung cancer

Lung cancer is the most commonly diagnosed cancer and the one that causes the most deaths worldwide, so there is a need for therapies that improve survival rates. Products derived from marine organisms are a source of novel and potent antitumor compounds, but they present the great obstacle of their obtaining from the natural environment and the problems associated with the synthesis and biological effects of chemical analogues. In this work, a Bengamide analogue (Bengamide II) was chemically synthesized and in vitro and in vivo studies were performed to determine its antitumor activity and mechanisms of action. It was shown to have potent antiproliferative activity in lung cancer lines in 2D and 3D models. In addition, Bengamide II-treated cells showed G2/M and G0/G1 cell cycle arrest, together with a decrease in the proliferation marker Ki67. As for the mechanism of action, the treatment was associated with increased LC3-II expression and production of acidic vesicles signaling autophagy. In addition, Bengamide II treatment was associated with caspase-3 activation and DNA fragmentation related to apoptosis. Furthermore, a reduction of VEGFA expression, related to angiogenesis, was also observed. In vivo studies showed that Bengamide II markedly reduced tumor volume and metastases increasing survival. Additionally, it revealed no systemic toxicity in in vivo models at the therapeutic doses used, which is essential for its future clinical use. Taken together, the chemically synthesized bengamide analogue Bengamide II, is a promising drug for lung cancer treatment showing relevant antitumor activity and significant safety.

Disturbing cytoskeleton by engineered nanomaterials for enhanced cancer therapeutics.

Cytoskeleton plays a significant role in the shape change, migration, movement, adhesion, cytokinesis, and phagocytosis of tumor cells. In clinical practice, some anti-cancer drugs achieve cytoskeletal therapeutic effects by acting on different cytoskeletal protein components. However, in the absence of cell-specific targeting, unnecessary cytoskeletal recombination in organisms would be disastrous, which would also bring about severe side effects during anticancer process. Nanomedicine have been proven to be superior to some small molecule drugs in cancer treatment due to better stability and targeting, and lower side effects. Therefore, this review summarized the recent developments of various nanomaterials disturbing cytoskeleton for enhanced cancer therapeutics, including carbon, noble metals, metal oxides, black phosphorus, calcium, silicon, polymers, peptides, and metal-organic frameworks, etc. A comprehensive analysis of the characteristics of cytoskeleton therapy as well as the future prospects and challenges towards clinical application were also discussed. We aim to drive on this emerging topic through refreshing perspectives based on our own work and what we have also learnt from others. This review will help researchers quickly understand relevant cytoskeletal therapeutic information to further advance the development of cancer nanomedicine.

Isolation, Characterization, and Antiproliferative Activity of Polymethoxy Flavones from Mentha dumetorum

Background: Natural products have been used commonly in the pharmaceutical industry as well as traditional medicine due to their bioactive contents. Objective: The objective of this study is to isolate the polymethoxy flavones (PMFs) and evaluate the antiproliferative activity. Methods: The PMFs were extracted from Mentha dumetorum with boiling hot water and then partitioned with hexane and the extract was subjected to chromatographic techniques such as Sephadex LH-20, silica gel, and preparative TLC, and HPLC to isolate the compounds. The structures of isolated compounds were elucidated by spectroscopic techniques such as 1H-NMR, 13C-NMR, LC-TOF-MS, and UV-Vis. The antiproliferative effects of isolated compounds were evaluated using a real-time cell analyzer–single plate (RTCA-SP) instrument against HeLa and HT29 cell lines. Results: The isolated PMFs were identified as xanthomicrol (1), 5-hydroxy-6,7,8,4'-tetrametoxy flavanone (2), 5-desmetil sinensetin (3), 5-demetil nobiletin (4), gardenin B (5), 5-hydroxy-6,7,8,3',4'- penta methoxy flavanone (6) and 5-hydroxy-6,7,4'-trimethoxy flavone (7). Compounds 2 and 5 were found to be the most active against both cell lines. Conclusion: The isolated compounds as well as the plant extract of Mentha dumetorum could be promising agents for the drug development process, especially drugs for cancer treatment. Moreover, isolation methods were developed for the corresponding compounds.

Molecular pathogenesis, mechanism and therapy of Cav1 in prostate cancer.

Prostate cancer is the second incidence of malignant tumors in men worldwide. Its incidence and mortality are increasing year by year. Enhanced expression of Cav1 in prostate cancer has been linked to both proliferation and metastasis of cancer cells, influencing disease progression. Dysregulation of the Cav1 gene shows a notable association with prostate cancer. Nevertheless, there is no systematicreview to report about molecular signal mechanism of Cav1 and drug treatment in prostate cancer. This article reviews the structure, physiological and pathological functions of Cav1, the pathogenic signaling pathways involved in prostate cancer, and the current drug treatment of prostate cancer. Cav1 mainly affects the occurrence of prostate cancer through AKT/mTOR, H-RAS/PLCε, CD147/MMPs and other pathways, as well as substance metabolism including lipid metabolism and aerobic glycolysis. Baicalein, simvastatin, triptolide and other drugs can effectively inhibit the growth of prostate cancer. As a biomarker of prostate cancer, Cav1 may provide a potential therapeutic target for the treatment of prostate cancer.

Myristicin Suppresses Gastric Cancer Growth via Targeting the EGFR/ ERK Signaling Pathway.

Myristicin is a type of natural compound showing anti-proliferative, anti-microbial, and anti-inflammatory effects. However, its role in gastric cancer treatment remains unknown. In this study, the effect of myristicin on gastric cancer as well as its underlying mechanism was investigated. Human gastric cancer cells were exposed to various concentrations of myristicin (0, 7.8125, 15.625, and 31.25 μM) for 48 h. Then CCK-8, fluorescence-activated cell sorting, and Hoechst staining were performed to evaluate the cell proliferation and apoptosis. The levels of proteins associated with cell cycle, apoptosis, endoplasmic reticulum (ER) stress, and EGFR/ERK signaling pathway were detected by western blot. JC-1 staining was conducted to determine the mitochondrial membrane potential. On the other hand, the effect of myristicin on gastric cancer growth and apoptosis was also determined in vivo. Myristicin retarded proliferation and induced ER stress and apoptosis in gastric cancer cells, with decreased expression of cyclins, increased Bax expression, activated caspases, and enhanced cytochrome C release and mitochondrial ROS. Furthermore, the EGFR/ERK signaling pathway was restrained by myristicin. In addition, EGFR over-expression abolished the inhibitory function of myristicin on proliferation, apoptosis, and ER stress. Also, myristicin inhibited the growth of gastric cancer cells as well as the EGFR/ERK signaling pathway in vivo. Myristicin exerts an anti-cancer effect on gastric cancer cells by restraining the EGFR/ ERK signaling pathway. It may have the potential to be applied as a novel drug in gastric cancer treatment.

Evaluation of the therapeutic efficacy of Vitex agnus-castus extract on cisplatin-induced hematotoxicity in female Wistar rats.

Cisplatin (CP) is a preferred drug for cancer treatment but it has dose-dependent side effects. Vitex agnus-castus (VAC) berry extract has antioxidant, free-radical scavenging, and anti-inflammatory activities. This study explored the mitigating effects of VAC extract (VACE) on acute hematotoxicity induced by CP in female Wistar rats. Female Wistar rats (n = 30) were randomly divided into five groups (n = 6/group). The normal control (NC) group received no treatment. The CP control group received CP (7 mg/kg.b.w. ip, single dose) and the drug control group (VACE-650) received VACE (650 mg/kg b.w. oral, daily) for 7 days. Both groups received a single dose of CP (7 mg/kg b.w. ip), followed by 350 and 650 mg/kg.b.w. of VACE daily orally (CPVACE-350 and CPVACE-650 groups, respectively) for 7 days. After a single dose of CP (7 mg/kg b.w.), the red blood cells (RBC), hematocrit (HCT), white blood cells (WBC), and platelets significantly decreased. In the VAC-350 group, the reduction in total WBC count was less than that in the VAC-650 group on the 3rd day. The RBC and HCT values of the VACE groups were better than that of the CP control, but the VACE-350 treatment group showed significant improvement only on the 3rd day. Our findings showed that VACE can mitigate CP-induced damage to peripheral blood cells at lower doses.

The immunostimulant effects of the rice ragged stunt virus genome on the growth and metastasis of breast cancer in mouse model

There are multiple treatment strategies that have been reported for breast cancer, while new and effective therapies against it are still necessary. Stimulating the immune system and its components against cancer cells is one of the unique treatment strategies of immunotherapy and long dsRNAs are immunostimulant in this regard. Based on bioinformatics approaches, a fragment of the Rice ragged stunt RNA virus genome was selected and synthesized according to its immunogenicity. Based on the in vitro transcription technique, dsRNA was synthesized and its binding ability to the PEI/PEI-Ac Polyethylenimine (PEI) or Acetylated polyethylenimine (PEI-Ac) was verified by the gel retardation assay. Then, the PEI-Ac was synthesized by adding acetyl groups to the PEI, and the results of the 1H NMR method indicated its successful synthesis. After cancer induction by 4 T1 cells in Balb/C mice, intraperitoneal (IP) and intratumoral (IT) treatment by the PEI/PEI-Ac-dsRNA were performed and the tumor growth inhibition was evaluated. Results demonstrated that PEI/PEI-Ac-dsRNA can lead to a decrease in tumor weight and volume in both the IP and IT routes. Also, by using macro-metastatic nodule counting and hematoxylin and eosin (H&E) staining we showed that PEI/PEI-Ac-dsRNA can prevent micro and macro-metastasis in the lung. Therefore, the PEI/PEI-Ac-dsRNA acts as an effective inhibitor of growth and metastasis of the breast cancer models. We showed that viral dsRNA can exert its antitumor properties by stimulating TNF-α and IFN-γ. In general, our results revealed that dsRNA derived from the plant virus genome stimulates the intrinsic immune system and can be a potential immune stimulant drug for cancer treatment.