Chemotherapeutic Effects Research Articles

Gallic Acid Alleviates Methotrexate‐Induced Oxidative Ovarian Damage in Rats

Although methotrexate (MTX) is an effective chemotherapeutic agent in the treatment of cancer, its use is limited due to the occurrence of systemic tissue toxicity, including those affecting the reproductive system. Gallic acid (GAL) is a phenolic compound that has been demonstrated to exert beneficial effects in a number of pathological conditions associated with oxidative stress (OS) in recent years. This study was designed to investigate the therapeutic potential of GAL in the treatment of ovarian damage caused by MTX. Adult female rats (n=30) were randomly allocated to five groups: control, MTX, MTX+GAL (2.5 and 5 mg/kg) and high-dose GAL only (5 mg/kg). In the MTX-containing groups, ovarian toxicity was induced by a single dose MTX (20 mg/kg) injection. In contrast, groups containing GAL received injection treatment for three days, starting on the second day. The levels of OS, inflammation and apoptosis in tissue samples collected on the fifth day of the experiment were quantified using spectrophotometric methods. The results showed that GAL treatment reduced the level of ovarian lipid peroxidation, inflammation, and apoptosis and promoted the ovarian antioxidant system in rats subjected to MTX. The results of this study indicate that GAL may have the potential to ameliorate MTX-associated oxidative and inflammatory ovarian damage. It is recommended that this ovoprotective effect of GAL be confirmed by more comprehensive preclinical studies.

Capturing Hydrophilic Chemotherapeutics Agents Into siRNA-Encapsulated Vesicle-Like Nanoparticles for Convenient ICB-Chemo Combination Therapy.

Clinical evidence has demonstrated that combining immune checkpoint blockade (ICB) therapy with chemotherapy significantly improves response rates to ICB therapy and therapeutic efficacy in various tumor types. However, a convenient method for achieving synergistic ICB therapy and chemotherapy with precise co-delivery of both agents is still highly desirable. In this study, a strategy for co-delivering small interfering RNA (siRNA) encapsulated in vesicle-like nanoparticles (VNPsiRNA) and chemotherapeutic drugs is aimed to develop. It is discovered that the hydrophilic chemotherapeutic drug mitoxantrone hydrochloride (MTO·2HCl) can be captured into VNPsiRNA. The resulting VNPsiRNACpMTO can simultaneously block immune checkpoints via RNA silencing and induce chemotherapeutic effects on tumor cells. The mechanism of MTO·2HCl is elucidates, captures, and demonstrates the superior therapeutic effect of VNPsiRNACpMTO through chemo-immunotherapy. This strategy can also be extended to deliver other hydrochloride anticancer drugs, such as doxorubicin hydrochloride (DOX·HCl), for achieving synergistic combination therapy. This study provides a facile strategy for enhancing combined ICB and chemotherapy via co-delivering siRNA and chemotherapeutic drugs, offering a promising approach to cancer treatment.

1,3,4-Oxadiazole: An Emerging Scaffold to Inhibit the Thymidine Phosphorylase as an Anticancer Agent.

Thymidine phosphorylase (TP), also referred to as "platelet-derived endothelial cell growth factor" is crucial to the pyrimidine salvage pathway. TP reversibly transforms thymidine into thymine and 2-deoxy-D-ribose-1-phosphate (dRib-1-P), which further degraded to 2-Deoxy-D-ribose (2DDR), which has both angiogenic and chemotactic activity. In several types of human cancer such as breast and colorectal malignancies, TP is abundantly expressed in response to biological disturbances like hypoxia, acidosis, chemotherapy, and radiation therapy. TP overexpression is highly associated with angiogenic factors such as vascular endothelial growth factor (VEGF), interleukins (ILs), matrix metalloproteases (MMPs), etc., which accelerate tumorigenesis, invasion, metastasis, immune response evasion, and resistant to apoptosis. Hence, TP is recognized as a key target for the development of new anticancer drugs. Heterocycles are the primary structural element of most chemotherapeutics. Even 75% of nitrogen-containing heterocyclic compounds are contributing to the pharmaceutical world. To create the bioactive molecule, medicinal chemists are concentrating on nitrogen-containing heterocyclic compounds such as pyrrole, pyrrolidine, pyridine, imidazole, pyrimidines, pyrazole, indole, quinoline, oxadiazole, benzimidazole, etc. The Oxadiazole motif stands out among all of them due to its enormous significance in medicinal chemistry. The main thrust area of this review is to explore the synthesis, SAR, and the significant role of 1,3,4-oxadiazole derivatives as a TP inhibitor for their chemotherapeutic effects.

Mesenchymal Stem Cells Target Gastric Cancer and Deliver Epirubicin via Tunneling Nanotubes for Enhanced Chemotherapy.

A reduced effective local concentration significantly contributes to the unsatisfactory therapeutic results of epirubicin in gastric cancer. Mesenchymal stem cells exhibit targeted chemotaxis towards solid tumors and form tunneling nanotubes with tumor cells, facilitating the delivery of various substances. This study demonstrates the novelty of mesenchymal stem cells in releasing epirubicin into gastric cancer cells through tunneling nanotubes. Epirubicin delivery to gastric cancer cells using mesenchymal stem cells. In vitro transwell migration assays, live cell tracking, and in vivo targeting assays were used to demonstrate the chemotaxis of mesenchymal stem cells towards gastric cancer. We verified the targeted chemotaxis of mesenchymal stem cells towards gastric cancer cells and the epirubicin loading ability using a high-content imaging system (Equipment type:Operetta CLS). Additionally, tunneling nanotube formation and the targeted release of epirubicin-loaded mesenchymal stem cells co-cultured with gastric cancer cells through mesenchymal stem cell-tunneling nanotubes into gastric cancer cells was observed using Operetta CLS. Mesenchymal stem cells demonstrated targeted chemotaxis towards gastric cancer, with effective epirubicin loading and tolerance. Co-culturing induced tunneling nanotube formation between these cells. Epirubicin-loaded mesenchymal stem cells were released into gastric cancer cells through tunneling nanotubes, significantly increasing their non-viability compared to the negative control group (p < 0.05). We identified a novel approach for precisely targeting epirubicin release in gastric cancer cells. Therefore, mesenchymal stem cell-tunneling nanotubes could serve as a potential tool for targeted delivery of drugs, enhancing their chemotherapeutic effects in cancer cells.

Intra-arterial chemoembolization as a component of neoadjuvant treatment of rectal cancer. Literature review

Interventional oncology is a rapidly evolving field of cancer treatment. Minimally invasive techniques, such as transarterial embolization with chemotherapeutic and radioactive agents, are common treatments and are found in many guidelines for the treatment of primary and metastatic liver lesions. It is known that the growth and development of a malignant neoplasm is primarily determined by angiogenesis. Rapid growth is ensured where the formation is directly related to the arterial bed. Therefore, when the drug is injected into the target vessel and providing tissue ischemia, it is possible to achieve a high degree of tumor pathomorphosis. This technique has an advantage for patients who, in some cases, cannot be treated surgically, and also increases the effectiveness of the chemotherapeutic effect. With the advent of necessary equipment in hospitals and the accumulation of experience in the use of minimally invasive interventions, it became possible to implement a new method of treating tumors of various localizations. In this review, we consider the results of domestic and foreign authors on the topic of intra-arterial chemoembolization before surgical treatment in patients with rectal cancer. It is noted that the analysis of the literature revealed a small number of works devoted to the chosen topic, despite the relevance of this problem for modern oncology.

Pyroptosis is not likely to play a major role in anthracycline-induced cytotoxicity in H9c2 cardiomyocytes and human cardiac endothelial cells

Abstract Background Although anthracyclines are widely used as effective chemotherapeutic agents, anthracycline-induced cardiotoxicity (AIC) causes significant morbidity and mortality. The precise mechanism of AIC remains elusive, although apoptosis may be involved. Recent research suggests pyroptosis, a programmed lytic cell death pathway, might also contribute to AIC. Although studies have focused on AIC in the myocardium, emerging evidence suggests that AIC may also affect vascular cells. Furthermore, the cytotoxicity of doxorubicin (DOX) or its supposed active metabolite, doxorubicinol (DOXOL), has not been widely investigated in cardiac vascular cells. Purpose This study examines the hypothesis that pyroptosis plays a role in DOX and DOXOL cytotoxicity in H9c2 immortalised rat cardiac myoblasts and two types of human cardiac endothelial cells. Methods In vitro experiments were conducted to ascertain dose-dependent toxicity in H9c2, and cardiac endothelial cells following treatment with DOX or DOXOL. The type of cell death was determined by assessing cell morphology and fluorescent staining with markers of apoptosis (Annexin V) and lytic cell death (Propidium Iodide PI) following DOX or DOXOL treatment in comparison to known inducers of pyroptosis (LPS &amp; Nigericin). Western blot experiments were conducted to study the expression of GSDMD (involved in pyroptosis), and caspase 3 (involved in apoptosis), following DOX or DOXOL. A human monocytic acute myeloid leukaemia cell line (THP-1 cells) was used as a positive control for pyroptosis. Results Dose-dependent cell death following DOX treatment was higher than with DOXOL in both H9c2 and cardiac endothelial cells. DOX caused apoptotic changes in all cell types. In contrast, DOXOL had weaker effects, inducing early apoptosis. No cleavage (activation) of GSDMD or caspase 3 was detected after DOX or DOXOL. Interestingly, in THP-1 cells, DOX induced predominantly apoptotic cell death, whereas DOXOL induced predominantly pyroptotic cell death, assessed both morphologically and by caspase 3 and GSDMD cleavage. Conclusion DOX and DOXOL primarily induce apoptotic cell death in H9c2 cardiomyocytes and cardiac endothelial cells. Interestingly, DOXOL, supposedly the active metabolite, was less cytotoxic than DOX. THP-1 cells undergo apoptotic or pyroptotic cell death with DOX or DOXOL, respectively. In conclusion, anthracycline-induced cytotoxicity is likely to be due to apoptotic injury rather than pyroptosis.

A Machine Learning-Optimized System for Pulsatile, Photo- and Chemotherapeutic Treatment Using Near-Infrared Responsive MoS2-Based Microparticles in a Breast Cancer Model.

Multimodal cancer therapies are often required for progressive cancers due to the high persistence and mortality of the disease and the negative systemic side effects of traditional therapeutic methods. Thus, the development of less invasive modalities for recurring treatment cycles is of clinical significance. Herein, a light-activatable microparticle system was developed for localized, pulsatile delivery of anticancer drugs with simultaneous thermal ablation by applying controlled ON-OFF thermal cycles using near-infrared laser irradiation. The system is composed of poly(caprolactone) microparticles of 200 μm size containing molybdenum disulfide (MoS2) nanosheets as the photothermal agent and hydrophilic doxorubicin or hydrophobic violacein, as model drugs. Upon irradiation, the nanosheets heat up to ≥50 °C leading to polymer softening and release of the drug. MoS2 nanosheets exhibit high photothermal conversion efficiency and require low-power laser irradiation. A machine learning algorithm was applied to acquire the optimal laser operation conditions. In a mouse subcutaneous model of 4T1 triple-negative breast cancer, 25 microparticles were intratumorally administered, and after 3-cycle laser treatment, the system conferred synergistic phototherapeutic and chemotherapeutic effects. Our on-demand, pulsatile synergistic treatment resulted in increased median survival up to 39 days post start of treatment compared to untreated mice, with complete eradication of the tumors at the primary site. Such a system is therapeutically relevant for patients in need of recurring cycles of treatment on small tumors, since it provides precise localization and low invasiveness and is not cross-resistant with other treatments.

Dual-Action Gemcitabine Delivery: Chitosan–Magnetite–Zeolite Capsules for Targeted Cancer Therapy and Antibacterial Defense

Cancer and infectious diseases are two of the world’s major public health problems. Gemcitabine (GEM) is an effective chemotherapeutic agent against several types of cancer. In this study, we developed macrocapsules incorporating GEM into a chitosan matrix blended with magnetite and zeolite by ionic gelation. Physicochemical characterization was performed using HRTEM-ED, XRD, FESEM–EDS, FT-IR, TGA, encapsulation efficiency (%E.E.), and release profiles at pHs 7.4 and 5.0. Cell viability tests against A549 and H1299 cell lines, and microbiological properties against staphylococcal strains were performed. Our results revealed the successful production of hemispherical capsules with an average diameter of 1.22 mm, a rough surface, and characteristic FT-IR material interaction bands. The macrocapsules showed a high GEM encapsulation efficiency of over 86% and controlled release over 24 h. Cell viability assays revealed that similar cytotoxic effects to free GEM were achieved with a 45-fold lower GEM concentration, suggesting reduced dosing requirements and potentially fewer side effects. Additionally, the macrocapsules demonstrated potent antimicrobial activity, reducing Staphylococcus epidermidis growth by over 90%. These results highlight the macrocapsules dual role as a chemotherapeutic and antimicrobial agent, offering a promising strategy for treating lung cancer in patients at risk of infectious diseases or who are immunosuppressed.

Targeting the 3D genome by anthracyclines for chemotherapeutic effects.

The chromatins are folded into three-dimensional (3D) structures inside cells, which coordinates the regulation of gene transcription by the non-coding regulatory elements. Aberrant chromatin 3D folding has been shown in many diseases, such as acute myeloid leukemia (AML), and may contribute to tumorigenesis. The anthracycline topoisomerase II inhibitors can induce histone eviction and DNA damage. We performed genome-wide high-resolution mapping of the chemotherapeutic effects of various clinically used anthracycline drugs. ATAC-seq was used to profile the histone eviction effects of different anthracyclines. TOP2A ChIP-seq was used to profile the potential DNA damage regions. Integrated analyses show that different anthracyclines have distinct target selectivity on epigenomic regions, based on their respective ATAC-seq and ChIP-seq profiles. We identified the underlying molecular mechanism that unique anthracycline variants selectively target chromatin looping anchors via disrupting CTCF binding, suggesting an additional potential therapeutic effect on the 3D genome. We further performed Hi-C experiments, and data from K562 cells treated with the selective anthracycline drugs indicate that the 3D chromatin organization is disrupted. Furthermore, AML patients receiving anthracycline drugs showed altered chromatin structures around potential looping anchors, which linked to distinct clinical outcomes. Our data indicate that anthracyclines are potent and selective epigenomic targeting drugs and can target the 3D genome for anticancer therapy, which could be used for personalized medicine to treat tumors with aberrant 3D chromatin structures.

Eradication of Large Tumors by Nanoscale Drug Self-Assembly.

Most patients with cancer are first diagnosed at an advanced disease stage, when tumors are already large and/or metastases are present. This circumstance has a negative impact on the prognosis and therapeutic effect of anticancer drugs. In this study, it is demonstrated that photosensitizer chlorin e6 and the photochemotherapy drug mitoxantrone self-assemble into relatively stable nanoassemblies (CM NAs) through hydrogen-bonding effect, π-π stacking, and hydrophobic interactions. Administration of CM NAs in combination with 660nm laser irradiation shows chemotherapeutic, photothermal, and photodynamic effects, causing tumor cell apoptosis and pyroptosis and enabling noninvasive tumor ablation without compromising the surrounding normal tissue. More importantly, treatment with CM NAs increases tumor immunogenicity, leading to a strong and long-term antitumor immune response that eradicates large tumors and provides long-term protection against tumor recurrence on various tumor models.

Identification and validation of an m7G-related lncRNAs signature for predicting prognosis, immune response and therapy landscapes in ovarian cancer.

Ovarian cancer is the most mortality malignancy in gynecology. N7-methylguanosine (m7G) is one of the most prevalent RNA modifications in the development and progression of cancer. The aim of this study is to investigate the effect of m7G-related lncRNA on ovarian cancer in terms of instruction prognosis and immunotherapy. After integrating and processing the RNA expression profiles with the clinical sample information in the TCGA database, we initially screened to the m7G-related lncRNAs by Spearman correlation analysis, and subsequently obtained a prognostic model constructed by five m7G-related lncRNAs with Univariate Cox analysis, LASSO regression analysis, and Multivariate Cox regression analysis, after which we further evaluated and validated the prognostic value of the model using Kaplan-Meier survival analysis, Principal component analysis, Nomogram, and ROC curve. In addition, based on this risk model, we explored the differentially enriched pathways and functions of the high and low risk groups, and characterized the immune cells, immune functions, gene mutations, and drug sensitivity between the two groups. After a series of rigorous filtering, we finally attained a prognostic risk model consisting of KRT7-AS, USP30-AS1, ZFHX4-AS1, ACAP2-IT1, and TWSG1-DT which is excellent in predicting the prognostic survival of ovarian cancer patients as well as existing as an independent prognostic factor. Moreover, the model has certain relevance in the immune cells and functions between high and low risk groups, and simultaneously, the signature has the role of guiding the option of immunotherapy and chemotherapeutic drugs. Altogether, our study established a tight connection between m7G-associated lncRNAs and ovarian cancer, with potential that the prognostic patterns contribute to steering the prognosis of ovarian cancer patients, measuring the efficacy of immunotherapeutic approaches, and detecting effective chemotherapeutic agents.

Sensitization of melanoma cells to standard chemotherapy: G-quadruplex binders as synergistic agents.

The use of chemotherapeutics has achieved considerable success in cancer therapy; however, their toxicity can severely impact patients' health. In this study, aiming to reduce the doses and potential side effects of traditional chemotherapeutics, we systematically treated A375MM human melanoma cells with seven clinically approved antineoplastic drugs, in combination with three well-characterized G-quadruplex (G4) ligands, using either simultaneous or sequential dosing schedules. Interestingly, the G4binders synergized with most of the investigated anticancer drugs, with the degree of synergism being strictly dependent on both the treatment schedule and the drug sequence employed. Notably, some of the synergistic combinations showed selective toxicity towardmelanoma cells over nontumorigenic human keratinocytes. Furthermore, immunofluorescence experiments highlighted the potential implication of G4 structures in the molecular mechanisms driving the synergistic interaction between some chemotherapeutics and G4 binders. Overall, our systematic study supports the combination of G4-interacting molecules with standard antineoplastic drugs as a promising antitumor strategy.

Design of Bionanomaterial of Chitosan Carbohydrate Polymer Composited with Broccoli Extract and Zinc Oxide Nanoparticles: Anticancer Activity in Human Osteosarcoma.

In the current research, a chitosan/broccoli extract/ZnO nanoparticle (CH/BE/ZnO) bionanocomposite was created. The physicochemical properties of CH/BE/ZnO bionanocomposite were investigated using a variety of methods, including field emission scanning electron microscopy (FESEM), elemental analysis (CHN-O), X-ray diffraction (XRD), Fourier transform infrared spectrum (FTIR), Brunauer-Emmett-Teller (BET), and transmission electron microscopy (TEM). The CH/BE/ZnO bionanocomposite's biological activity was assessed by examining its cytotoxicity capabilities against a bone cancer cell line (MG63). The total pore volume and specific surface area of CH/BE/ZnO are 0.134 cm3/g and 16.99 m2/g, respectively. The IC50 results for CH/BE/ZnO bionanocomposite in bone cancer investigations using the MTT test against the MG63 cell line was 115μg/mL. The results indicate that the CH/BE/ZnO bionanocomposite is an effective chemotherapeutic agent against human osteosarcoma. The CH/BE/ZnO bionanocomposite showed high performance and structure, which means innovating nanomaterial agents for biological applications in the future.

In Vivo Chemosuppressive Effects of Kolaviron on 7,12-Dimethylbenzanthracene-Induced Mammary Lesions are Associated with Changes in Levels of Estrogen Receptor-α, CYP 1A1, Proinflammatory Cytokines, and Alterations to Metabolic Pathways Implicated in Mammary Carcinogenesis.

Garcinia kola is a medicinal food commonly consumed in Sub-Sahara Africa, for which Kolaviron (KV) is the active portion. As a follow-up to our earlier chemopreventive studies, we investigated the chemotherapeutic effects of KV on experimentally induced mammary carcinogenesis in female Wistar rats. Mammary carcinogenesis was induced using 80 mg/kg of 7,12-dimethylbenzanthracene (DMBA) administered by oral gavage. One hundred-fifty days post-DMBA induction, estrogen receptor-α (ER-α) levels were determined in the experimental rats before treatment with KV commenced. Treatment was done using 50, 100, and 200 mg/kg KV thrice a week for 4 weeks, after which the experiment was terminated. Significantly higher levels of estrogen receptor-α, CYP 1A1, malondialdehyde, formation of lobular neoplastic cells, epithelial hyperplasia, lymphocyte infiltration, and increased cytokine (interleukin-6 and tumor necrosis factor-α) activity were observed in DMBA-induced rats, which were attenuated in KV-treated rats. Tyrosine metabolism was exclusively enriched in DMBA-induced rats in contrast to KV-treated rats. Collectively, the results point to the chemotherapeutic potential of KV.

Polydopamine-functionalized calcium-deficient hydroxyapatite 3D-printed scaffold with sustained doxorubicin release for synergistic chemo-photothermal therapy of osteosarcoma and accelerated bone regeneration

Interior bone-tissue regeneration and rapid tumor recurrence post-resection are critical challenges in osteosarcoma and other bone cancers. Conventional bone tissue engineering scaffolds lack inhibitory effects on bone tumor recurrence. Herein, multifunctional scaffolds (named DOX/PDA@CDHA) were designed through the spontaneous polymerization of Dopamine (PDA) on the surface of Calcium Deficient Hydroxyapatite (CDHA) scaffolds, followed by in situ loading of the chemotherapeutic drug Doxorubicin (DOX). The PDA coating endowed the scaffolds with significant photothermal properties, while the gradual release of DOX provided an effective chemotherapeutic effect. The on-demand release of DOX at tumor sites, triggered by dual stimulation (near-infrared (NIR) light and the acidic pH typical of tumor microenvironments), specifically targets cancer cells, thereby mitigating systemic side effects. These unique characteristics facilitated effective osteosarcoma eradication both in vitro and in vivo. Moreover, the scaffold's composition, which mimics the mineral phase of natural bone and is enhanced by PDA's biocompatibility, promotes critical osteogenic and angiogenic processes. This facilitates not only tumor eradication but also the regeneration of healthy bone tissue. Collectively, this study presents a potent candidate for the regeneration of bone defects induced by osteosarcoma.

Abstract C026: Analyzing the effect of annonacin on diverse breast cancer cell lines as a potential therapeutic agent for triple negative breast cancer

Abstract Triple negative breast cancer (TNBC) grows and spreads faster than most invasive breast cancer. Additionally, available treatment options and prognosis are poor. Due to limited available treatment options, finding the appropriate and effective chemotherapeutic agents for TNBC patients is a key research effort. Importantly, differential therapeutic response reported between ethnic and racial groups has prompted a need for better treatment modalities. In previous studies, Annonacin (Annona Muricata-a plant with anti-inflammatory properties) has been tested and shown to have cytotoxic effects on various cancer cell lines. The objective of this study is to analyze the effects of Annonacin across racial backgrounds. For this study, we used two TNBC cell lines; MDA-MB-468 (derived from a 51-year old African American female) and MDA-MB-231 (derived from a 40-year old Caucasian American female). Our hypothesis is that Annonacin will inhibit cell proliferation in both TNBC cell lines, potentially giving rise to a beneficial therapeutic agent that will address health disparity. To assess the efficacy of Annonacin, cell viability was measured using a MTT assay providing IC50 values for each cell line. The 50% inhibitory concentrations were 8.5 uM and 15 uM for MDA-MB-468 and MDA-MB-231, respectively. Cell cycle analysis was performed using flow cytometry to assess the effect of Annonacin on the induction of cell cycle arrest. MDA-MB-231 was arrested at the G2 phase in a dose-dependent manner. MDA-MB-468 was arrested at the G2 phase at 7.5 uM. Induction of apoptosis was at 15 uM (MDA-MB-468) and 30uM (MDA-MB-231). In addition, protein expression for both cell lines, as determined by western blotting analysis, showed an increase of the cell cycle regulatory proteins cyclin B1 and CDK1 and the apoptotic protein caspase-3. Results for this small sample size demonstrate efficacy of treatment for both racial populations. Further studies analyzing the effect of Annonacin on additional diverse TNBC cell lines, organoids, and patient derived xenografts will advance the progression of alternative treatments for all patients with TNBC. Citation Format: Jennifer Hernandez-Torres, Kelly Argueta Guzman. Analyzing the effect of annonacin on diverse breast cancer cell lines as a potential therapeutic agent for triple negative breast cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C026.

Potential Chemotherapeutic Effect of Coenzyme Q10 Against Liver Injury in a Leukemia Rat Model by 7,12-Dimethylbenz[a]anthracene

Potential Chemotherapeutic Effect of Coenzyme Q10 Against Liver Injury in a Leukemia Rat Model by 7,12-Dimethylbenz[a]anthracene

Decorating Delivery Vehicles Using Hyaluronic Acid Oligosaccharides Enables Active Targeting Toward Cancer and Minimizes Adverse Effect of Chemotherapeutics.

The major drawback of conventional chemotherapeutic treatment is the non-specificity or inability to ascertain and target cancerous cells directly. In this study, an active targeting strategy that is poised to carry the anticancer agents to the desired sites for therapeutic action while avoiding toxicity to normal organs is provided. The active targeting of delivery vehicles is achieved by ligand-receptor interactions, in particular the specific binding between hyaluronic acid oligosaccharides (oHAs) and CD44 receptors. This study first prepares oHAs by the size-exclusion chromatography and utilizes them to decorate chitosan (CTS) as basic materials (oHAs-CTS) for drug delivery, then fabricates oHAs-CTS into micro/nanoscale carriers to encapsulate agents for cancer chemotherapy. The oHAs-CTS micro/nanocarriers exhibit high drug encapsulation efficiency (58-87%), and the drug releases present a sustained behavior. Notably, oHAs-CTS delivery vehicles display an enhanced active targeting toward cancers and alleviate the cytotoxic effects on normal cells. Additionally, in vivo results show that drug-laden oHAs-CTS nanocarriers demonstrate a significant inhibitory effect on 4 T1 tumors without any toxicity to the major organs. Taken together, the findings highlight the potential of oHAs-CTS micro/nanospheres as delivery vehicles with enhanced active targeted capability toward cancers and minimized adverse effects of chemotherapeutic agents for cancer treatment.

Metal Oxide Nanoparticles Exhibit Anti-Acanthamoeba castellanii Properties by Inducing Necrotic Cell Death.

The treatment of amoebic infections is often problematic, largely due to delayed diagnosis, amoebae transformation into resistant cyst form, and lack of availability of effective chemotherapeutic agents. Herein, we determined anti-Acanthamoeba castellanii properties ofthree metal oxide nanoparticles (TiO2, ZrO2, and Al2O3). Amoebicidal assays were performed to determine whether metal oxide nanoparticles inhibit amoebae viability. Encystation assays were performed to test whether metal oxide nanoparticles inhibit cyst formation. By measuring lactate dehydrogenase release, cytotoxicity assays were performed to determine human cell damage. Hoechst 33342/PI staining was performed to determine programmed cell death (apoptosis) and necrosis in A. castellanii. TiO2-NPs significantly inhibited amoebae viability as observed through amoebicidal assays, as well as inhibited their phenotypic transformation as evident using encystation assays, and showed limited human cell damage as observed by measuring lactate dehydrogenase assays. Furthermore, TiO2-NPs altered parasite membranes and resulted in necrotic cell death as determined using double staining cell death assays with Hoechst33342/Propidium iodide (PI) observed through chromatin condensation. These findings suggest that TiO2-NPs offers a potential viable avenue in the rationaledevelopment oftherapeutic interventions against Acanthamoeba infections.

Icariin inhibits cisplatin-induced ovarian toxicity via modulating NF-κB and PTEN/AKT/mTOR/AMPK axis.

Cisplatin (CP) is a highly effective broad-spectrum chemotherapeutic agent for several solid tumors. However, its clinical use is associated with ovarian toxicity. Icariin (ICA) is a bioactive flavonoid of Epimedium brevicornum with reported protective activities against inflammation, oxidative stress and ovarian failure. This study aimed to explore the protective effects of ICA against CP-associated ovarian toxicity in rats. Rats were randomized into five groups and treated for 17 days: control, ICA (10 mg/kg/day, for 17 days. p.o.), CP (6 mg/kg, i.p. on days 7 and 14), CP + ICA (CP 6 mg/kg i.p. on days 7 and 14 and ICA 5 mg/kg p.o. daily), and CP + ICA (CP 6 mg/kg i.p. on days 7 and 14 and ICA 10 mg/kg p.o. daily). Our results indicated that ICA effectively improved ovarian reserve as indicated by attenuating CP-induced histolopathological changes and enhancing serum anti-müllerian hormone (AMH). Furthermore, co-administration of ICA with CP showed restoration of the oxidant-anti-oxidant balance in ovarian tissues, evidenced by decreased malondialdehyde (MDA) concentrations and elevated superoxide dismutase (SOD) and catalase (CAT) activities. Also, ICA suppressed ovarian inflammation as evidenced by down-regulation of the expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and nuclear factor kappa B (NF-κB). ICA inhibited ovarian apoptosis in CP-treated rats by down-regulation of CASP3 and Bax and up-regulation of Bcl-2 mRNA expression. Further, ICA enhanced PTEN, p-AKT, p-mTOR, and p-AMPKα expression. In conclusion, ICA possesses a protective activity against CP-induced ovarian toxicity in rats by exhibiting antioxidant, antiinflammatory, anti-apoptotic activities and modulating NF-κB expression and PTEN/AKT/mTOR/AMPK axis in ovarian tissues.