Significant Anticancer Effects Research Articles

Anticancer and Chemosensitizing Effects of WEE‐1 Kinase Inhibitor MK‐1775 in Triple Negative (MB‐231) Breast Cancer Cells

Current breast cancer classification included cells that express estrogen (ER) and progesterone (PR) receptors, those with ERBB2 (HER‐2/Neu) amplification, and those without expression of ER, PR, or amplification of ERBB2 (referred to as triple‐negative or basal‐like breast cancer). Triple negative breast cancers are generally more difficult to treat, are known to be more aggressive and with poor prognosis. Several molecular mechanisms have been identified as potential targets for development of drugs to treat breast cancer including cell cycle checkpoints kinases. The G2/M cell‐cycle protein tyrosine kinase, Wee‐1, plays a crucial role in the checkpoint arrest for DNA repair before mitotic entry. Under normal conditions, cells repair damaged DNA during G1 arrest; however, cancer cells often have a deficient G1/S (p53) checkpoint and depend on a functional G2/M checkpoint for DNA repair. MK‐1775 is a well‐characterized Wee‐1 kinase inhibitor with significant evidence supporting its potential use as anti‐cancer and/or chemosensitizing drug. Working hypothesis proposed for this project was that use of Wee‐1 kinase inhibitors in breast cancer cells can result in profound and significant anticancer and chemosensitizing effects. In order to test this hypothesis, we show previously in a series of dose response experiments using DNA‐Damaging agents or treatments (DNA‐dt: Ex. Cisplatin, 5‐Fluororacil and Doxorubicin) alone and/or in combination with MK‐1775. To continue testing this hypothesis an Immunoblotting bioassay is currently developed for continue monitoring the effects of MK‐1775 in several biochemical markers in triple negative breast cancer cell line. Preliminary results indicated that biochemical marker in triple negative cell line, are time dependent with the different combination of DNA‐dt alone and/or in combination with MK‐1775. Initial preliminary results indicated taken together, our preliminary results are consistent with a potential role of Wee‐1 kinase inhibitors like MK‐17175 as anticancer and/or chemosensitizing agents against triple‐negative or basal‐like breast cancer cells.Support or Funding InformationThe project described was supported by NIGMS/INBRE award P20 GM103475; U.S. Department of Education Title V grant number P031S130068 and Puerto Rico Science Technology and Research Trust. The content is solely the responsibility of the authors and does not necessarily represent the official view of any of the supporting agencies.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Alantolactone induces gastric cancer BGC-823 cell apoptosis by regulating reactive oxygen species generation and the AKT signaling pathway.

Alantolactone (ALT), a natural sesquiterpene lactone, has been suggested to exert anti-cancer activities in various cancer cell lines. However, the effects and mechanisms of action of ALT in human gastric cancer remains to be elucidated. In the present study, the effects of ALT on BGC-823 cells were examined and the underlying molecular mechanisms associated with these effects were investigated. Cell viability was detected by using an MTT assay. Cell cycle, cell apoptosis and the level of reactive oxygen species (ROS) were assessed by flow cytometry, and the expression levels of proteins of interest were analyzed by western blot assay. The results demonstrated that ALT triggered apoptosis and induced G0/G1 phase arrest in a dose-dependent manner. Furthermore, the expression level of the anti-apoptosis protein Bcl-2 was downregulated, and expression of the pro-apoptosis proteins Bax and cleaved PARP were significantly upregulated. The cell cycle-associated proteins cyclin-dependent kinase inhibitor 1 and cyclin-dependent kinase inhibitor 1B were also increased, while cyclin D1 was deceased. In addition, ALT induced apoptosis via the inhibition of RAC-alpha serine/threonine-protein kinase (AKT) signaling and ROS generation, which was effectively inhibited by the ROS scavenger, N-acetyl cysteine. Therefore, the results from the present study indicated that the ROS-mediated inhibition of the AKT signaling pathway serves an important role in ALT-induced apoptosis in BGC-823 cells. In conclusion, the results demonstrated that ALT exerted significant anti-cancer effects against gastric cancer cells in vitro.

Cordycepin suppresses cell proliferation and migration by targeting CLEC2 in human gastric cancer cells via Akt signaling pathway

PurposeGastric cancer is a common malignancy worldwide, and is associated with high morbidity and mortality rates. Cordycepin is a 3′-deoxyadenosine drug with significant anti-cancer effects. The aim of this study was to determine the molecular mechanisms underlying cordycepin action on gastric cancer cell proliferation and migration. MethodsThe human gastric cancer cell lines MGC-803 and HGC-27 were treated with different concentrations of cordycepin (25 μM, 50 μM, 100 μM and 5 μM, 25 μM and 50 μM) for 48 h. Cell proliferation was assessed by MTT and colony formation assays, and in vitro migration by the wound healing and transwell assays. In addition, Flow Cytometry was used to detect the cell cycle and apoptosis. RT-PCR and Western blotting were used to evaluate the expression levels of key factors. ResultsCordycepin significantly inhibited gastric cancer cell proliferation and migration in a dose-dependent manner, in addition to inducing apoptosis and arresting the cell cycle at the G2 phase. Mechanistically, cordycepin targeted the PI3K/Akt signaling pathway by significantly altering the expression levels/activation of several key mediators, and upregulated the anti-metastatic factor CLEC2. ConclusionCordycepin inhibited the proliferation and migration of gastric cancer cells by upregulating CLEC2 via the Akt signaling pathway.

Size-adjustable micelles co-loaded with a chemotherapeutic agent and an autophagy inhibitor for enhancing cancer treatment via increased tumor retention

Autophagy plays a key role in the stress response of tumor cells, which contributes to cancer cell survival and resistance to chemotherapy by degrading cytoplasmic proteins to provide energy and clear the hazardous substances. Therefore, combined treatment of chemotherapeutics and autophagy inhibitors is thought to obtain a desirable antitumor effect. Nanoparticles (NPs) show potential in tumor-targeting drug delivery because of the enhanced permeability and retention (EPR) effect. However, NPs with fixed particle size cannot achieve optimal delivery effect. Herein, a strategy based on Cu (I)-catalyzed click chemistry-triggered aggregation of azide/alkyne-modified micelles was developed for the co-delivery of the chemotherapeutic drug doxorubicin (Dox) and the autophagy inhibitor wortmannin (Wtmn). In vitro experiments showed that the size of micelles increased in a time-dependent manner, which enhanced micelle accumulation in both B16F10 and 4 T1 cells. The fluorescence resonance energy transfer (FRET) experiment and biodistribution study further demonstrated that the aggregation of micelles through click cycloaddition significantly improved the accumulation of drug-loading micelles at the tumor region. Furthermore, the decreased amount of autophagosomes observed by transmission electron microscopy (TEM), the declined expression of LC3-II, and the increased level of p62 by western blotting and immunohistochemistry (IHC) confirmed the obvious inhibition of autophagy induced by Dox/Wtmn co-loaded size-adjustable micelles, which had a synergistic effect in cancer suppression. In addition, the co-loaded size-adjustable micelles showed outstanding cytotoxicity and antitumor effect. Therefore, this strategy effectively suppressed melanoma and breast cancer in mice. Statement of SignificanceThe therapeutic effects of chemotherapy can be limited by autophagy; hence, combined use of autophagy inhibitors with chemotherapeutics achieves desirable anticancer efficacy. In the present study, we designed size-adjustable micelles by modifying the click reaction substrate azide group and the alkyne group on the surface of micelles, and subsequently, the autophagy inhibitor wortmannin and the chemotherapeutic drug doxorubicin were co-loaded. The micelles could aggregate by click reaction at the tumor site when the catalysts were intratumorally injected. The results showed that the size-adjustable micelles achieved efficient drug delivery, penetration, and retention in tumors; through the combined effect of wortmannin-mediated autophagy inhibition and doxorubicin-mediated cytotoxicity, this strategy exerted significant anticancer effect in melanoma and breast cancer treatment.

Morusinol Exhibits Selective and Potent Antitumor Activity Against Human Liver Carcinoma by Inducing Autophagy, G2/M Cell Cycle Arrest, Inhibition of Cell Invasion and Migration, and Targeting of Ras/MEK/ERK Pathway.

BackgroundLiver cancer is one of the most commonly diagnosed cancers across the globe. The treatment is often difficult as it is diagnosed mostly at advanced stages. Moreover, the lack efficacious and less toxic drugs are another problem in the treatment of liver cancer. Against this background, in this study we evaluated the anticancer activity of morusinol against SK-HEP-1 liver cancer cells.Material/MethodsThe proliferation rate of liver cancer cell line was investigated by MTT assay. Autophagy was detected by transmission electron microscopy and cell cycle analysis was performed by flow cytometry. The protein expression was examined by Western blotting.ResultsMorusinol inhibited the proliferation of liver cancer SK-HEP-1 cells, with an IC50 of 20 μM against the SK-HEP-1 liver cancer cells. Further investigations indicated that the antiproliferative effects of morusinol are due to initiation of autophagy and G2/M cell cycle arrest, which was also associated with altered expression of several important proteins. Morusinol also suppressed the migration and invasion of SK-HEP-1 liver cancer cells, and it suppressed the expression of p-MEK and p-ERK, leading to suppression of the Raf/MEK/ERK signalling cascade.ConclusionsWe found that morusinol exerts significant anticancer and autophagic effects on liver cancer cells and our results suggest the potential of morusinol in treatment of liver cancer.

Scaling up of levan yield in Bacillus subtilis M and cytotoxicity study on levan and its derivatives

This study focused on kinetics of levan yield by Bacillus subtilis M, in a 150L stirred tank bioreactor under controlled pH conditions. The optimized production medium was composed of (g/L): commercial sucrose 100.0, yeast extract 2.0, K2HPO4 3.0 and MgSO4⋅7H2O 0.2; an increase in both carbohydrates consumption and cell growth depended on increasing the size of the stirred tank bioreactor from 16L to 150L. The highest levansucrase production (63.4 U/mL) and levan yield of 47g/L was obtained after 24h. Also, the specific levan yield (Yp/x) which reflects the cell productivity increased with the size increase of the stirred tank bioreactor and reached its maximum value of about 29.4g/g cells. These results suggested that B.subtilis M could play an important role in levan yield on a large scale in the future. Chemical modifications of B.subtilis M crude levan (CL) into sulfated (SL), phosphorylated (PL), and carboxymethylated levans (CML) were done. The difference in CL structure and its derivatives was detected by FT-IR transmission spectrum. The cytotoxicity of CL and its derivatives were evaluated by HepGII, Mcf-7 and CaCo-2. In general most tested levans forms had no significant cytotoxicity effect. In fact, the carboxymethylated and phosphrylated forms had a lower anti-cancer effect than CL. On the other hand, SL had the highest cytotoxicity showing SL had a significant anti-cancer effect. The results of cytotoxicity and cell viability were statistically analyzed using three-way ANOVA.

Synthesis and cytotoxicity of selenium nanoparticles stabilized by α-D-glucan from Castanea mollissima Blume.

A 1,6-α-D-glucan (CPA) with a high molecular weight of 2.0 × 103 kDa was isolated from the fruits of Castanea mollissima Blume. CPA showed good water solubility, low side effects on normal cells, and moderate cytotoxicity on cancer cells. Selenium nanoparticles (SeNPs) possess significant anticancer effects, but poor water solubility and dispersity. Therefore, an effective nanocomposite was designed in order to enhance the stability and anticancer effects of SeNPs decorated with CPA. Water soluble and dispersed selenium nanoparticles (CPA-SeNPs) were fabricated using CPA and Na2SeO3 by redox reaction with ascorbic acid. The average diameter of CPA-SeNPs was 53.7 ± 4.0 with a Se content of approximately 171.4 mg/g. CPA-SeNPs showed a significant anti-proliferative effect on HeLa cells in vitro. Since these NPs could induce apoptosis and S phase arrest. The apoptotic pathway triggered by CPA-SeNPs on HeLa cells was also characterized as induced by reactive oxygen species (ROS) overproduction, mitochondrial dysfunction and activation of caspase-3. This study suggested that CPA-SeNPs could be developed as a potential candidate in cancer treatment, especially against human cervical cancer.

GSH-responsive anti-mitotic cell penetrating peptide-linked podophyllotoxin conjugate for improving water solubility and targeted synergistic drug delivery

Podophyllotoxin (PPT) is a chemotherapeutic agent which has shown significant anti-cancer effects through inhibiting microtubule assembly. However, because of the poor water solubility and obvious side effects, PPT cannot be used in clinical cancer therapy. In order to solve these problems, a novel glutathione-responsive PPT conjugate has been synthesized in which PPT was linked to an anti-mitotic cell penetrating peptide (PRA) via a disulfide linkage. In particular, the as-prepared PPT-PRA conjugate can self-assemble into vesicle in water, furthermore, another anti-cancer drug (doxorubicin was chosen as an example) can be loaded in the vesicle for synergistic drug delivery. For better cancer cells targeting, the vesicle was then modified with folic acid (FA). The results indicated that the as-prepared FA modified drug-loaded vesicle not only could overcome the poor water solubility and side effects of PPT but also exhibited targeted toxicity and synergistic therapeutic effect.

Monofunctional supramolecular Pt(II) complexes: Synthesis, single crystal structure, anticancer activity, E. coli growth retardation and DNA interaction study

Two new monofunctional mono-metallic trans-Pt(II)(salicylaldimine)(pyridine)·BF4 (C1) and supramolecular dimetallic trans-(Pt(II)(salicylaldimine))2(4,4-bipyridine)·2BF4 (C2) complexes were designed and synthesized through ancillary chloride ligand exchange strategy and structurally characterized by spectroscopic, spectrophotometric and single crystal X-ray analyses. The solid-state structure analyses revealed interactions between the coordination planes, inter-molecular H-bonding, bonding in the ligand hydrogen and BF4 anions and supramolecular interactions with solvent molecules in crystal packing. The in vitro anticancer effect of these complexes was investigated in breast (MCF-7) and liver (HepG2) cancer cells. Both these complexes showed significant anticancer effect comparable to cisplatin. Similarly, the effect of these complexes on Escherichia coli (E. coli) growth retardation was also analyzed and the results revealed stronger growth retardation effect and elongated morphology of bacterial cells in similar fashion as observed for cisplatin. The DNA interaction of C1 and C2 was investigated by gel electrophoresis using pET28 as target DNA. These complexes retarded migration of DNA across the gel showing their interaction with DNA.

In Vitro Anticancer Activity of Extracellular Vesicles (EVs) Secreted by Gingival Mesenchymal Stromal Cells Primed with Paclitaxel.

Interdental papilla are an interesting source of mesenchymal stromal cells (GinPaMSCs), which are easy to isolate and expand in vitro. In our laboratory, GinPaMSCs were isolated, expanded, and characterized by studying their secretome before and after priming with paclitaxel (PTX). The secretome of GinPaMSCs did not affect the growth of cancer cell lines tested in vitro, whereas the secretome of GinPaMSCs primed with paclitaxel (GinPaMSCs/PTX) exerted a significant anticancer effect. GinPaMSCs were able to uptake and then release paclitaxel in amounts pharmacologically effective against cancer cells, as demonstrated in vitro by the direct activity of GinPaMSCs/PTX and their secretome against both human pancreatic carcinoma and squamous carcinoma cells. PTX was associated with extracellular vesicles (EVs) secreted by cells (EVs/PTX), suggesting that PTX is incorporated into exosomes during their biogenesis. The isolation of mesenchymal stromal cells (MSCs) from gingiva is less invasive than that from other tissues (such as bone marrow and fat), and GinPaMSCs provide an optimal substrate for drug-priming to obtain EVs/PTX having anticancer activity. This research may contribute to develop new strategies of cell-mediated drug delivery by EVs that are easy to store without losing function, and could have a superior safety profile in therapy.

Cancer Cells Treated by Clusters of Copper Oxide Doped Calcium Silicate.

Purpose: Different compositions of copper oxide (CuO)-doped calcium silicate clusters were used to treat the cancer cells. Methods: The influence of CuO content on the morphology, drug delivering ability, physicochemical properties and cytotoxicity was investigated. Results: The microcrystalline structure revealed the decrement of the size from (20-36 nm) to (5-7 nm) depending on the copper content percentages. Drug delivering ability of doxycycline hyclate (Dox) was down regulated from 58% to 28%in the presence of the CuO. The inclusion of CuO and Dox didn’t show any remarkable changes on the physicochemical properties of the CuO-doped calcium silicate nanoparticles. Conclusion: The CuO-doped calcium silicate sample (5 weight %) exhibited great cytotoxicity against the tested cell lines compared to the CuO-free sample. CuO-doped materials displayed significant anticancer effect; this sheds light on its implication in the treatment of cancer.

The anticancer effects and mechanisms of fucoxanthin combined with other drugs.

Fucoxanthin (Fx) is a characteristic carotenoid present in brown seaweed that has been shown to have various benefits, including anticancer effects. In vitro studies demonstrated these various effects, including the suppression of cell viability, the promotion of apoptosis, and antiangiogenic, antiproliferative, and antimetastatic activity. Interestingly, combinations of Fx with other drugs have better effects than either Fx or other drugs alone. Although the antiproliferative and cancer prevention activities of the combination of Fx and other drugs are still unclear, several effects have been discovered, including the induction of apoptosis, cell cycle arrest at G1/G0, enhanced gap junctional intercellular communication, and the induction of autophagy via various mechanisms, such as decreasing P-gp, activating the CYP3A4 promoter, increasing reactive oxygen species and cellular uptake and suppressing the PI3K/Akt/NFκB pathway. In this review, we address the anticancer effects and mechanisms of the combination of Fx and other drugs in different types of cancer. The relevant literature from PubMed and Web of Science databases is reviewed in this article. Fx combined with other drugs could enhance the effect of both Fx and the other drug or reduce the dose without reducing the effect, which may create more effective and less harmful therapeutic strategies. Fx combined with other drugs has significant anticancer effects by various mechanisms and could be a potential therapeutic strategy for different types of cancer.

Delivery of Doxorubicin from Hyaluronic Acid-Modified Glutathione-Responsive Ferrocene Micelles for Combination Cancer Therapy.

A combination of different chemotherapy approaches can obtain the best response for many cancers. However, the greatest challenge is the development of a nanoparticle formulation that can encapsulate different chemotherapeutic agents to achieve the proper synergetic chemotherapy for the tumor. Here, amphiphilic ferrocenium-tetradecyl (Fe-C14) was constructed to form cationic micelles in an aqueous solution via self-assembly. Then, it was coated by hyaluronic acid (HA) through electrostatic interactions to generate HA-Fe-C14 micelles. The HA-Fe-C14 micelles were used to deliver doxorubicin (DOX), and it showed that the DOX could be released rapidly under a high-GSH tumor environment. The HA-Fe-C14/DOX micelles were able to accumulate efficiently in tumor and showed significant anticancer effect both in vitro and in vivo. These results suggest that HA-Fe-C14/DOX micelles are a useful drug delivery system that enhances synergic antitumor treatment effects.

Recent Updates on the Phytochemistry and Pharmacological Properties of Phlomis viscosa Poiret.

Crude ethanolic extracts from Phlomis viscosa Poiret leaves from the Judea region (Israel) are renowned for their remarkable geroprotective properties: anti-inflammatory, anti-diabetic, and anti-cancer. A phytochemical investigation carried out in this study revealed that the tested plant might belong to a particular distinct chemotype because its phytochemicals are different from compounds that were mentioned in the literature. Among the compounds identified by us was diosmin, the synthetic derivatives of which were further obtained and investigated. In particular, activities of the isolated compounds and synthesized diosmin derivatives were assessed. Our results revealed that the following compounds significantly lessened secretion of some pro-inflammatory cytokines: diosmin, himachala-2-diene, and 5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl) chromen-4-one. In addition, diosmin, synthesized diosmin derivatives, and some identified terpenes were found to have anti-diabetic activities. A significant anti-cancer effect of the whole extract on U-87 (human glioblastoma carcinoma cells line) and MCF7 (human breast carcinoma cell line) was also demonstrated, and it was better than that of DOX (doxorubicin). Collectively, the results obtained in the in vitro models suggest a wide spectrum of beneficial bioactivities of the extract and its active compounds.

Oxymatrine Attenuates Tumor Growth and Deactivates STAT5 Signaling in a Lung Cancer Xenograft Model.

Oxymatrine (OMT) is a major alkaloid found in radix Sophorae flavescentis extract and has been reported to exhibit various pharmacological activities. We elucidated the detailed molecular mechanism(s) underlying the therapeutic actions of OMT in non-small cell lung cancer (NSCLC) cells and a xenograft mouse model. Because the STAT5 signaling cascade has a significant role in regulating cell proliferation and survival in tumor cells, we hypothesized that OMT may disrupt this signaling cascade to exert its anticancer effects. We found that OMT can inhibit the constitutive activation of STAT5 by suppressing the activation of JAK1/2 and c-Src, nuclear localization, as well as STAT5 binding to DNA in A549 cells and abrogated IL-6-induced STAT5 phosphorylation in H1299 cells. We also report that a sub-optimal concentration of OMT when used in combination with a low dose of paclitaxel produced significant anti-cancer effects by inhibiting cell proliferation and causing substantial apoptosis. In a preclinical lung cancer mouse model, OMT when used in combination with paclitaxel produced a significant reduction in tumor volume. These results suggest that OMT in combination with paclitaxel can cause an attenuation of lung cancer growth both in vitro and in vivo.

Cytotoxic effects of S-(+)-Carvone on selected human cancer cell lines

S-(+)-Carvone (S-CVN), the main constituent of Caraway seed (Carum carvi L.Umbelliferae), has been reported to show significant anticancer and chemopreventive effects against several cancer types. The current study aimed to evaluate the cytotoxic effects of S-CVN on four different human cancer cell lines: ovarian cancer (SW-626), triple negative breast cancer (BT-20), prostate cancer (PC-3) and lymphoma (RAJI). Using MTS proliferation assay, S-CVN showed significant concentration-dependent anti-proliferative effects against the chosen cancer cell lines, with IC50 values of 147,117,199 and 228?M in SW-626, PC-3, BT-20 and RAJI, respectively. Mechanistically, S-CVN with its ?,?-unsaturated carbonyl functionality has the potential to interact with cellular nucleophilic functional groups through Michael’s addition type of reaction. The covalent interaction may explain the observed anti-proliferative activity. To further understand the mechanism of S-CVN cytotoxicity, glutathione (GSH and GSSG) were added to SW-626 cell line as pre- and co-treatments with S-CVN. According to results, the cell viability was enhanced and the cytotoxic effect of S-CVN was extremely decreased using a range of GSH/GSSG concentrations (50 -1000?M). Moreover, the interaction between GSH and S-CVN was further confirmed by using thin layer chromatography (TLC). This is presumably attributed to the fact that the nucleophilic thiol function in GSH interacts with S-CVN ?,?-unsaturated ketone moiety at ?-C. The obtained data suggests that the reactivity of the electrophilic functionality of S-CVN plays a crucial role in its cytotoxicity.

Repurposing Brigatinib for the Treatment of Colorectal Cancer Based on Inhibition of ER-phagy.

Rationale: The sustained and severe endoplasmic reticulum (ER) stress in cancer cells may contribute to apoptotic cell death, thus representing a potential target for cancer therapy. Brigatinib is an anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of ALK-positive non-small-cell lung cancer (NSCLC). However, it remains unclear if brigatinib has alternative model of action to exert antitumor effect in ALK-negative cancers.Methods: ALK-positive NSCLC cells and various human ALK-negative cancer cells, especially human colorectal cancer (CRC) cells were used to examine the tumor suppression effect of brigatinib alone or in combination with autophagy inhibitors in vitro and in vivo. A variety of biochemical assays were conducted to elucidate the underlying mechanisms of brigatinib in CRC cells.Results: Here, we show the significant anti-cancer effect of brigatinib in CRC through induction of apoptosis by sustained ER stress. Mechanistically, brigatinib induces ER stress via promoting the interaction between ubiquitin-specific peptidase 5 (USP5), a deubiquitinase, and oxysterol-binding protein-related protein 8 (ORP8), leading to ORP8 deubiquitination, accumulation and growth inhibition. Furthermore, we find that brigatinib-mediated ER stress simultaneously induces autophagic response via ER-phagy that acts as a protective mechanism to relieve excessive ER stress. As such, combination of brigatinib with autophagy inhibitors significantly enhances the anti-CRC effect of brigatinib both in vitro and in vivo, supporting the repurposing of brigatinib in CRC, independently of ALK.Conclusion: The unearthed new molecular action of brigatinib suggests that therapeutic modulation of ER stress and autophagy might represent a valid strategy to treat CRC and perhaps other ALK-negative cancers.

Phenethyl Isothiocyanate Inhibits Nasopharyngeal Carcinoma Cell Growth and Invasion

The dietary compound phenethyl isothiocyanate (PEITC), is an active component of cruciferous vegetables and markedly inhibits the growth of a variety of tumors. However, its role in human nasopharyngeal carcinoma (NPC) is obscure. The aim of the present study was to elucidate the possible mechanisms whereby PEITC exhibited anticancer properties in human nasopharyngeal carcinoma NPC-TW01 cells in vitro. The experiment results exhibited that in a dose- and time-dependent manner treatment of NPC-TW01 cells with PEITC significantly inhibited cell proliferation, promoted apoptosis with concurrent G2/M cell cycle arrest and inhibited cell invasion in a dose-dependent manner. These effects were accompanied by significant alterations in the expression levels of key proteins associated with pro-survival signaling pathways, including PI3K, Akt, ERK, NF-κB, Bcl, Bax, cyclin B, CDK4 and CDK6. Significantly, these effects were not reflected in 16HBE normal human bronchial epithelial cells, indicating a safe range of treatment concentrations between 0 and 10 μM PEITC. In conclusion, PEITC exhibited significant anticancer effects against human nasopharyngeal carcinoma cells in vitro with low toxicological impact on normal bronchial epithelial cells. This was achieved through dysregulation of key proteins involved in the occurrence and development of tumors, and this approach may be applied to the clinical treatment of NPC and in drug screening.

Glucose targeted therapy against liver hepatocellular carcinoma: In vivo study

In this study, glucose-targeted and glucose-free micelles composed of a diblock copolymer of poly(ethylene glycol)-b-poly(lactide) that encapsulated superparamagnetic iron oxide (SPIO) and doxorubicin (DOX) in their hydrophobic core were fabricated. Glucose micelles showed 5.01 ± 0.3% drug loading content and 103 ± 4.0 nm size. We also endeavoured to observe the cellular uptake of these targeted and non-targeted micelles. The anticancer efficacy of the targeted, non-targeted micelles and free doxorubicin at the equivalent dose of 32 mg/kg were evaluated on the nude mice bearing tumours. Glucose micelles exhibited significant anticancer effects than free doxorubicin and non-targeted micelles. It was noteworthy that free doxorubicin showed toxicity at the site of injection. H&E staining of targeted micelles demonstrated remarkable changes in tumour architecture, also exerted higher percentage of necrosis (82.5%). Prussian blue staining revealed that tumour tissues with glucose DOX/SPIO micelles displayed much higher iron density than the non-targeted micelles, which could be employed for imaging tumour growth in the future. The data revealed that glucose targeted therapy can inhibit hepatocellular carcinoma when compared to non-targeted micelles. These specialised targeted micelles can serve as a theranostic agent hence, suggesting a useful targeted therapeutic and imaging strategy against liver cancer.

Protein Pump Inhibitors Esomeprazole and Pantoprazole Increase the Chemosensitivity of CML cells against Imatinib

Introduction: Proton pump inhibitors (PPIs) largely used drug to treat gastroesophageal disease such as gastric ulcers. Moreover, in recent years, several studies suggest that PPIs have important anti-cancer effect in monotherapy and or combination with chemotherapy. Objective: The aim of this study was to investigate whether esomeprazole and pantoprazole exhibit anti-cancer effect alone or could enhance chemosensitivity of CML cell line K562 to imatinib. Method: Human chronic myeloid leukemia (CML) cells were cultured and treated with different concentrations of esomeprazole, pantoprazole, and imatinib alone. Also these cells exposed to imatinib + esomeprazole and imatinib + pantoprazole combinations, respectively and incubated 24 h. The antiproliferative activities of the (PPIs) alone or in combination of imatinib was evaluated using the XTT colorimetric assay. Results: According to experimental data, neither PPIs showed any cytotoxic­ity on the K562 cell line at all concentrations except at 500 and 1000 µM. However, when combined with imatinib separately, they were found to have significant anti-cancer effects on K562 cells when compared to cell lines treated with imatinib alone (p<0.05). Conclusions: Taken together, the inhibition of V-ATPase via esomeprazole and pantoprazole might enhance the chemosensitivity of imatinib in CML cells. However, further studies are needed to be able to utilize PPIs in CML.