Antineoplastic Effects Research Articles

Maraviroc/cisplatin combination inhibits gastric cancer tumoroid growth and improves mice survival

BackgroundGastric cancer (GC) is a significant cancer-related cause of death worldwide. GC’s most used chemotherapeutic regimen is based on platinum drugs such as cisplatin (CDDP). However, CDDP chemoresistance reduces the survival rate of advanced GC. The immune C-C chemokine receptor type 5 (CCR5) have been proposed as a pivotal factor in cancer progression since its blockade has been linked with antineoplastic effects on tumor cell proliferation; nevertheless, its role in the chemoresistance of GC has not been elucidated. This study aimed to determine the effects induced by the CCR5 using Maraviroc (MVC), a highly selective CCR5 antagonist, on CDDP-resistant AGS cells (AGS R-CDDP), tumoroids (3D tumor spheroids), and animal models.ResultsThe combined CDDP and MVC treatment reduced cell viability and inhibited tumoroid formation in AGS R-CDDP cells. The effects of the MVC/CDDP combination on apoptosis and cell cycle progression were correlated with the increase in CDDP (dose-dependent). The mRNA levels of C-C Motif Chemokine Ligand 5 (CCL5), the main ligand for CCR5, decreased significantly in cells treated with the MVC/CDDP combination. MVC in the MVC/CDDP combination improved the survival rate and biochemical parameters of CDDP-treated mice by reducing the side effects of CDDP alone.ConclusionsThis finding suggests that MVC/CDDP combination could be a potential complementary therapy for GC.

Pharmacodynamic characterization and evaluation of oxidative stress effects of digitoxigenin derivatives on HeLa cells.

Cancer is a leading cause of death worldwide and its treatment is hampered by the lack of specificity and side effects of current drugs. Cardiotonic steroids (CTS) interact with Na+/K+-ATPase (NKA) and induce antineoplastic effects, but their narrow therapeutic window is key limiting factor. The synthesis of digitoxigenin derivatives with glycosidic unit modifications is a promising approach to develop more selective and effective antitumor agents. This study aimed to compare the pharmacological properties as well as the cytotoxic effects of digitoxigenin-α-L-amiceto-pyranoside and digitoxigenin-α-L-rhamno-pyranoside and to evaluate the mechanism of these derivatives in oxidative conditions in HeLa cells. The rhamnose derivative increased the binding affinity and inhibitory effect of digitoxigenin by approximately 5-15 times, unlike the amicetose derivative. Despite this difference, both compounds similarly increased H2O2 levels, induced membrane lipid peroxidation, and reduced GSH levels and SOD activity at nanomolar concentrations. This study highlights the importance of the sugar moiety in CTS structure for NKA binding and demonstrates that a primary mechanism of cytotoxicity of digitoxigenin derivatives may involve cellular oxidative stress, underscoring their potential as therapeutic agents for cancer treatment.

Combination of oxabicycloheptene sulfonate (OBHS) and antidiabetic drugs synergistically inhibits proliferation in human breast cancer cells

Abstract Objectives Oxabicycloheptene sulfonate (OBHS), a selective estrogen receptor modulator (SERM), demonstrates the potential to exert antineoplastic effects and modulate abnormal glycometabolism in BC cells. However, mono-chemotherapy therapy doesn’t always achieve full anticancer effects. Therefore, the present study aimed to evaluate the effect of combining OBHS with 2-deoxy-d-glucose (2-DG) or metformin on BC in an attempt to establish effective new combinations. Methods Impacts of OBHS alone and the combinations on cell cycle progression, cell viability, mitochondrial function, apoptosis, epithelial-mesenchymal transition (EMT)-associated gene levels, and the concentrations of glucose, lactate, and seven glycolysis kinases. Results Our findings demonstrate that both combinations involving OBHS significantly reduced BC cell viability and proliferation. Besides, the synergy of their combinations in MCF-7 cells (10 μmol/L OBHS and 20 μmol/L 2-DG or 10 μmol/L metformin) and T47D cells (30 μmol/L OBHS and 25 μmol/L 2-DG or 20 μmol/L metformin) on the loss of cell mitochondrial integrity, the triggering of mitochondria-mediated cell apoptosis, and potentially metabolic regulation were shown compared to each drug alone. Furthermore, in regulating tumor cell metastasis, the combination of OBHS and two antidiabetic drugs synergistically suppressed the expression of mesenchymal cell markers within BC cells in comparison with monotherapy. Conclusions Based on the findings, the synergistic effect of OBHS and 2-DG/metformin on cytotoxicity may be mediated through intrinsic mitochondria-mediated cell apoptosis to inhibit cell proliferation and reprogram the glycometabolism, which achieved the possible anticancer effect. This is an indication that OBHS combined with 2-DG/metformin was a potentially effective treatment strategy for estrogen receptor (ER)-positive BC.

Levetiracetam and valproic acid in glioma: antiseizure and potential antineoplastic effects.

Seizures are a frequent complication in glioma. Incidence of brain tumor-related epilepsy (BTRE) in high-grade glioma (HGG) is an estimated > 25% and in low-grade glioma (LGG) is approximately 72%. Two first-line antiseizure medications (ASMs) for BTRE include levetiracetam (LEV) and valproic acid (VPA). Use of VPA has decreased because of a broader side effect profile, potential interaction with chemotherapeutic drugs, and availability of newer generation agents. In refractory BTRE, LEV and VPA may be prescribed together to enhance seizure control. VPA and LEV have gained attention for their purported antineoplastic effects and synergistic role with temozolomide. VPA is suggested to modulate anticancer activity in vitro through multiple mechanisms. In addition, retrospective studies indicate increased overall survival in patients with epileptogenic HGGs who are managed with LEV or VPA rather than other ASMs. However, these studies have numerous limitations. It is also reported that patients with glioma and a seizure history have a longer survival. This extended survival, if one exists, may be only observed in certain gliomas with corresponding patient characteristics. We provide a brief overview of the management of BTRE, VPA and LEV as anticonvulsants and antineoplastics, and the factors that may be associated with survival in epileptogenic glioma.

Smart release injectable hydrogel co-loaded with liposomal combretastatin A4 and doxorubicin nanogel for local combinational drug delivery: A preclinical study.

Surgical resection and postoperative adjuvant chemotherapy have enhanced the outlook for breast cancer patients. However, tumor relapse and serious side effects of chemotherapy continue to impact patients' quality of life. Designing injectable composite hydrogel made of biodegradable polymers providing sustained release of antiangiogenic and chemotherapeutic agents might play a vital role in elimination of cancer cells. In this regard, we developed dextran based composite hydrogel incorporating doxorubicin-loaded dual-sensitive pH-redox nanogels (DOX-DSNG) and combretastatin A4 (CA4) loaded liposomes which undergo rapid disassembly in cancer cells. CA4 prevents tubulin polymerization and thus inhibits angiogenesis by binding to vascular endothelial tubulin. The results showed that DOX-DSNGs were negatively charged and 144.8±0.85nm in size. Besides, the size of CA4 loaded liposomes were 102.35±4.22nm and were negatively charged. Encapsulation efficiency of DOX-DSNGs and CA4 loaded liposomes were 100% and 89%, respectively. After loading into the hydrogel structure, doxorubicin and CA4 were gradually released from the composite hydrogel for up to 21days. DOX-DSNGs and CA4 loaded liposomes showed a dose-dependent cytotoxic effect against 4T1 breast cancer cells. Thereafter, the anti-neoplastic effect and survival study of the composite hydrogel was evaluated in vivo in tumor-bearing mice. The composite hydrogel significantly reduced tumor volume (from 116mm3 to 38mm3) with negligible organ damage, while showed lower cardiotoxicity in 28days. In conclusion, our results revealed that injectable composite dextran-based hydrogel incorporated with DOX-DSNG and CA4 loaded liposomes could be used as an efficient delivery platform for combination therapies in treatment of solid tumors.

Collective total synthesis of chartreusin derivatives and bioactivity investigations.

Capitalizing on Hauser annulation and Yu glycosylation, the chemical synthesis of chartreusin-type aromatic polycyclic polyketide glycosides has been investigated, culminating in the successful establishment of chemical approaches toward chartreusin derivatives with intricate chemical structures but promising bioactivities. Based on the chemical synthesis strategy, the first and collective chemical syntheses of chartreusin, D329C, and elsamicins A and B have been accomplished. The chemical strategy was featured by two complementary routes to secure chartarin 10-O-monosaccharide glycosides, the key intermediates in chartreusin derivative synthesis, as well as the highly stereoselective construction of the difficult glycosidic linkages. Through the synthetic investigations, viable donors and acceptors of 3-C-methyl-branched sugars were determined for the first time. Moreover, facilitated by the established chemical synthetic strategy, the cytotoxic activities of chartreusin derivatives against human cancer cell lines were assessed and profound antineoplastic effects for chartreusin and elsamicins A and B were recorded. Based on RNA-seq analysis, the underlying working mechanisms against ES-2 cells were investigated, and the appended sugar chain-determined function mechanisms were disclosed.

<i>In vivo</i> antitumor effects of bis-benzimidazole derivatives in mouse melanoma and lung cancer models

BACKGROUND: The development of new antitumor agents on the basis of benzimidazoles opens new opportunities for treatment of the malignant tumors, including those refractory to conventional therapies. The benzimidazole derivatives demonstrate wide spectrum of biological activities, specifically antineoplastic effects, and high-level cytotoxicity toward human’s tumor cell lines. The exploration of antineoplastic effects of new synthetic benzimidazole derivatives in in vivo models of tumor growth will help the development of the effective doses and cancer treatment regimens with the use of such compounds. AIM: To assess the antineoplastic effects of the benzimidazole derivatives — monomeric compound MB2Py(Ac) and dimeric compound DB2Py(3) — in the continuous cellular models of Lewis lung carcinoma (LLC) and melanoma B16 in mice. MATERIALS AND METHODS: In vivo assessment of antineoplastic effects was performed in the continuous mouse models of Lewis lung carcinoma (LLC) and B16 melanoma after a single intravenous injection of MB2Py(Ac) and DB2Py(3). Irinotecan was used as a comparator drug. Antitumor effects were measured via standard parameters, such as tumor growth inhibition (TGI%) and tumor growth rate (TGR). RESULTS: The study compounds DB2Py(3) and MB2Py(Ac) used in the study doses and regimen demonstrated mild antitumor effect in the model of murine solid tumors (TGI 50%). In melanoma B16 model, the maximum tumor growth inhibition was 15% and 38.5%, respectively, for MB2Py(Ac) and DB2Py(3). In the lung carcinoma model, the mild effect was observed, e.g. 8% for MB2Py(Ac) and 23.4% for DB2Py(3). The effect of the comparator drug, irinotecan, was more expressive, although short-term. In particular, TGI achieved 52.5% for melanoma B16 and 34.5% for Lewis lung carcinoma (LLC). In general, melanoma B16 was more sensitive to the effects of both bis-benzimidazoles and irinotecan, compared to the lung carcinoma LLC. CONCLUSION: This study shows that the dimeric compound DB2Py(3) was the most promising among three study substances in the models of melanoma and lung carcinoma in mice. Nevertheless, its high toxicity imposes the necessity of further optimization for the clinical use. The substance MB2Py(Ac) demonstrated lowest efficacy, although it may be also explored in the modified treatment regimens.

Photoprotective effects of quercetin on photoaging-induced rats

Purpose Photoaging is characterised by cutaneous changes caused by exposure to ultraviolet light over time. Quercetin is a bioflavanoid with antioxidant, antineoplastic, and anti-inflammatory effects. This study investigated the therapeutic effects of topical quercetin on photoaging, a phenomenon not previously studied in ultraviolet A (UVA)-induced photoaging. Methods A total of 40 rats were randomly categorised into 5 groups, each comprising 8 rats. A photoaging model was induced by applying UVA to the dorsal region of all rats, except for the negative control group. Topical 0.1% retinoic acid was applied to one UVA group, topical 0.3% quercetin to another UVA group, and both agents were applied in combination to yet another UVA group 5 days a week for 8 weeks. Subsequently, wrinkle values were measured, reactive oxygen species (ROS) and matrix metalloproteinase-1 (MMP-1) levels were analysed, and histopathological parameters were examined. Results The wrinkle value of the UVA group was found to be significantly higher than that of the UVA + Quercetin group. Collagen damage was lower in the UVA + Quercetin group than in the UVA group, although this difference was not statistically significant. Compared with the UVA + Retinoic Acid group, the UVA + Quercetin group exhibited a more significant decrease in inflammation. MMP-1 values were considerably higher in the UVA + Retinoic Acid and UVA + Quercetin + Retinoic Acid groups as well as in the UVA + Quercetin group compared with the control and UVA groups. Conclusion The present study showed that quercetin can be utilised in the treatment of photoaging, especially when combined with retinoic acid.

Tropisetron-Induced Apoptosis: A Study on SKOV3 Cell Viability and Gene Expression

Background: Ovarian tumors account for 1% of all childhood neoplasms and are the most common genital neoplasm in children. Considering the role of serotonin in the promotion of tumor growth and metastasis in some cancers, tropisetron as a 5-hydroxytryptamine (5-HT3) receptor antagonist can exert anti-neoplastic effects. The current study seeks to determine the association between the use of tropisetron and ovarian cancer­cell lines (SKOV3) by evaluating apoptotic regulators. Materials and Methods: In this experimental study, after the addition of tropisetron to SKOV3 cancer cells at the concentrations of 1, 10, and 100 μM, the MTT assay was employed to assess the cell viability percentage within 24, 48, and 72 hours. The level of expression of Bcl2 and Bax genes after 24 hours were determined by Real Time-PCR, and Caspase 3 enzyme activity was measured by the ELISA method. Differences between groups were statistically analyzed by one-way analysis of variance (ANOVA). A p-value less than 0.05 is considered to be statistically significant. Results: Based on the MTT test, tropisetron significantly decreased the viability of SKOV3 cancer cells. It decreased the levels of Bcl2 expression according to real-time PCR results (P =0.0015) but increased the expression levels of Bax (P = 0.011) in SKOV3 cells. Both caspase-3 enzyme activity and the ratio of Bax to Bcl2 expression (Bax/Bcl2) were increased (P = 0.008 and P = 0.011, respectively). Conclusion: Tropisetron could inhibit tumor cell growth via apoptosis induction and exert proapoptotic effects in an ovarian cancer ¬cell line. Therefore, it seems that it can be considered as a possible chemotherapy drug for ovarian cancer. However, more studies should be conducted in this regard.

Anticarcinogenic effects of ursodeoxycholic acid in pancreatic adenocarcinoma cell models.

Changes to the composition of the microbiome in neoplasia, is termed oncobiosis, may affect tumor behavior through the changes to the secretion of bacterial metabolites. In this study we show, that ursodeoxycholic acid (UDCA), a bacterial metabolite, has cytostatic properties in pancreatic adenocarcinoma cell (PDAC) models. UDCA in concentrations corresponding to the human serum reference range suppressed PDAC cell proliferation. UDCA inhibited the expression of epithelial mesenchymal transition (EMT)-related markers and invasion capacity of PDAC cells. UDCA treatment increased oxidative/nitrosative stress by reducing the expression of nuclear factor, erythroid 2-like 2 (NRF2), inducing inducible nitric oxide synthase (iNOS) and nitrotyrosine levels and enhancing lipid peroxidation. Furthermore, UDCA reduced the expression of cancer stem cell markers and the proportion of cancer stem cells. Suppression of oxidative stress by antioxidants, blunted the UDCA-induced reduction in cancer stemness. Finally, we showed that UDCA induced mitochondrial oxidative metabolism. UDCA did not modulate the effectiveness of chemotherapy agents used in the chemotherapy treatment of pancreatic adenocarcinoma. The antineoplastic effects of UDCA, observed here, may contribute to the induction of cytostasis in PDAC cell models by providing a more oxidative/nitrosative environment.

The Skin-Lightening Power of Tirbanibulin 1% Ointment.

Tirbanibulin 1% ointment has been licensed to treat non-hyperkeratotic actinic keratosis (AK) on the face and scalp in adults. Recent evidence suggests that, besides the antineoplastic effect, tirbanibulin may also confer substantial cosmetic benefits to patients. We report a single-center retrospective study of patients affected by solar lentigines (SLs) and AKs in the context of field cancerization treated with tirbanibulin 1% ointment. Among 42 patients, 35% (n = 15) experienced complete clearance of SLs, while partial clearance was observed in 50% (n = 21) of patients. Regarding AKs, complete and partial clearance were observed in 52% (n = 22) and 40% (n = 17) of patients, respectively. Major study limitations are the small sample size and the absence of a control group. Our results suggest that tirbanibulin 1% ointment may offer the dual benefit of treating AKs while simultaneously lightening aesthetically bothersome and difficult-to-treat lesions like SLs with just 5 days of application.

An in-silico approach to target Breast cancer with novel phytochemicals

Aging leads to the manifestation of various diseases. Cancer being one of the major illness that is associated with the age. Breast cancer is still a relatively global health concern as the leading cancer cause of death among women. The current study also utilizes an in-silico approach to discover and characterize new phytochemicals as potential therapeutic agents to breast cancer. Here, we explore the molecular basis driving the makeup of breast cancer, with an emphasis on the PI3K/AKT/mTOR pathway, a well-known signaling cascade implicated in cell growth and therapy response. Two candidates (Thalidasine (-8.80 Kcal/mol) and 7-Epiclusianone (-8.62 Kcal/mol)) were found to be promising leads displaying high binding affinity and therapeutic potential through screening a diverse library of phytochemicals against key breast cancer target proteins. These phytochemicals exhibit diverse antineoplastic effects as cell proliferation, angiogenesis, and metastasis inhibitors, and/or as inducers of apoptosis. Besides, their ability to specifically target breast cancer stem cells and to increase sensitivity to traditional therapies make them an appealing option for breast cancer adjuvant therapy. Taken together our data suggest that these phytochemicals should be further studied alone and in novel nano formulations that enhance bioavailability and reduce toxicity. This study adds to the evidence for the potential role of natural products in breast cancer and the role of lifestyle in cancer prevention.

Exploring the therapeutic potency of cryptotanshinone in cervical cancer: a multi-omics and network pharmacology approach.

Cervical cancer remains a significant challenge in oncology with an escalating demand for novel therapeutic strategies that can navigate the complexities of its pathophysiology. This study elucidated the antineoplastic effects of cryptotanshinone, a derivative of danshen (Salvia miltiorrhiza), a herb widely utilized in traditional Chinese medicine practices. Employing a comprehensive multi-omics approach, including transcriptomic, proteomic, and bioinformatics analyses, we investigated the potential effects of cryptotanshinone on cervical cancer through data mining and computational analysis. Our results demonstrated that the potential of cryptotanshinone to disrupted cancer cell proliferation and induced apoptosis may be ascribed to its modulation of gene expression and interaction with specific protein networks. Furthermore, network pharmacology and pathway enrichment analyses identified critical hubs and signaling pathways, suggesting a multi-targeted mechanism of action. Furthermore, the establishment of a prognostic model, which is founded upon differentially expressed genes linked to cryptotanshinone treatment, underscores its promising role as both a prognostic biomarker and a therapeutic agent. These insights pave the way for the integration of cryptotanshinone into therapeutic regimens, offering a promising avenue for enhancing the efficacy of cervical cancer treatment and patient outcomes.

Theoretical-Cheminformatic Study of Four Indolylphytoquinones, Prospective Anticancer Candidates.

Background/Objectives: Breast cancer is a disease with a high mortality rate worldwide; consequently, urgent achievements are required to design new greener drugs, leaving natural products and their derivatives as good options. A constant antineoplastic effect has been observed when the phytoproduct contains an indole fragment. Methods: Therefore, the objective of this work was to carry out a thoughtful computational study to perform an appropriate evaluation of four novel molecules of the class of the 3-indolylquinones as phytodrug candidates for antineoplastic activity: thymoquinone (TQ), 2,6-dimethoxy-1,4-benzoquinone (DMQ), 2,3-dimethoxy-5-methyl-1,4-benzoquinone (DMMQ), and 2,5-dihydroxy-1,4-benzoquinone (DHQ). It is important to highlight that the obtained computational results of the target compounds were compared-correlated with the theoretical and experimental literature data previously reported of several indolylquinones: indolylperezone, indolylisoperezone, indolylmenadione, and indolylplumbagin (IE-IH, respectively). Results: The results revealed that the studied structures possibly presented antineoplastic activity, in addition to the fact that the reactivity parameters showed that two of the evaluated compounds have the option to present IC50 values lower than or similar to 25 mg/mL, activity like that of indolylisoperezone; moreover, they show molecular coupling to PARP-1. Finally, the prediction of the calculated physicochemical parameters coincides with the Lipinski and Veber rules, indicating that the adsorption, metabolism, and toxicity parameters are acceptable for the studied compounds, obtaining high drug score values. Conclusions: Finally, a comparison between the proposed molecules and others previously synthesized was appropriately performed, establishing that the synthesis of the studied compounds and the determination of their pharmacological properties in an experimental manner are of interest.

Antineoplastic effect of doxorubizen in vitro in continuous and primary human anaplastic thyroid cancer cells.

New drugs are needed for the therapy of anaplastic thyroid cancer (ATC). This study aims to investigate doxorubizen (a dual-action structural hybrid (chimera) of doxorubicin (Dox) and DNA methylating drug temozolomide), in comparison with Dox, and alone or in combination with lenvatinib in ATC 8305C cells, and in primary human ATC cell cultures (pATC). We have investigated doxorubizen, Dox, and lenvatinib on 5 different pATC and in continuous 8305C cell line in vitro, evaluating their effect on cells proliferation by WST-1, apoptosis (Hoechst ad Annexin V assays) and migration (Chemicon QCM™ 96-well Migration Assay). The results have demonstrated: (1) a significant antiproliferative and proapoptotic effect of doxorubizen in 8305C and in pATC; (2) a significant antiproliferative and proapoptotic effect of Dox in pATC, and in 8305C; (3) the antineoplastic effect of lenvatinib in 8305C and in pATC; (4) a stronger antiproliferative and proapoptotic effect of doxorubizen than that of Dox, or lenvatinib; (5) that doxorubizen induced an inhibition of migration in pATC stronger than that of Dox, or lenvatinib; (6) that doxorubizen is able to synergize in vitro with lenvatinib increasing the antiproliferative effect, while doxorubizen alone is the primary factor that promotes the proapoptotic impact. We have first shown that doxorubizen has a potent antineoplastic effect in vitro in 8305C and in 5 different pATC, and that can synergize with lenvatinib. These results open the way to a future evaluation of the antineoplastic effect of doxorubizen in ATC patients.

Nanoengineering of Phosphate/Phosphonate Drugs via Competitive Replacement with Metal-Phenolic Networks to Overcome Breast Tumor with Lung and Bone Metastasis.

Phosphate and phosphonate drugs are vital in building organisms, regulating physiological processes, and exhibiting diverse biological activities, including antiviral, antibacterial, antineoplastic, and enzyme-inhibitory effects. However, their therapeutic potential is limited by the lack of advanced nanoengineering technologies. Herein, a competitive coordination strategy for nanoengineering phosphate/phosphonate drugs is introduced. By leveraging the difference in coordination capabilities between polyphenols and phosphates/phosphonates with metal ions, various phosphate/phosphonate-based nanodrugs using metal-phenolic networks (MPNs) as templates and phosphate/phosphonate drugs as competitive agents are constructed. The dynamic nature of these coordination bonds imparts stimuli-responsiveness to the nanodrugs, allowing for targeted release and therapy. As a proof of concept, Fe3+ and galangin are used to form the MPN template, zoledronic acid and cGAMP as competitive agents, and DOX as the loaded drug to construct DOX@Fe-galangin@Fe-zoledronic acid-cGAMP nanodrugs. The results demonstrate that, by triggering pyroptosis and activating the cGAS-STING pathway, the nanodrugs exhibit potent cytotoxicity and accurate selectivity in eradicating orthotopic breast tumors, and activate an antitumor immune response against lung and bone metastases. Because the competitive coordination strategy is applicable to a variety of phosphate/phosphonate agents, it holds significant potential for enhancing the clinical efficacy of phosphate/phosphonate drugs and advancing nanodrug development for complex therapeutic applications.

Extraction, characterization, and antineoplastic effect of Macadamia nut extracts against cutaneous melanoma cells: a comprehensive study focused on SK-MEL-28 cells

In this study the potential of macadamia nut extracts against cutaneous melanoma cells was evaluated. The extracts were obtained through ultrasound-assisted extraction (UAE), where the effects of solid–liquid ratio, irradiation power, and temperature were assessed. Additionally, pressurized ethanol extraction (PEE) was performed, focusing on the impact of pressure, flow rate, and temperature. In both methods, a gas chromatography was used to characterize the extracts in terms of fatty acids. To evaluate the antineoplastic effect, SK-MEL-28 cells were treated with different concentrations of extracts (0.01–10 mg.mL−1) for 24 h. The MTT assay was used to assess cell viability. Furthermore, mitochondrial transmembrane potential and apoptotic bodies formation were evaluated. The highest global yield value obtained by UAE and PEE was 52.73 % and 38.84 %, respectively. The chemical characterization indicated that the main fatty acids were the methyl cis-9 oleate followed by methyl palmitoleate, methyl palmitate. With respect to the antineoplastic effect, both macadamia extracts significantly reduced melanoma cell viability, lowered mitochondrial transmembrane potential, and induced the formation of apoptotic bodies. Extract from UAE had superior antineoplastic effect than extract PEE. This fact is based on the influence of extraction techniques on the concentration of extracted compounds. The results suggest that macadamia extracts have potential to be used as adjuvant therapy in melanoma context.

1,5- diaryl pyrazole-loaded chitosan nanoparticles as COX-2 inhibitors, mitigate neoplastic growth by regulating NF-κB pathway in-vivo zebrafish model

Non-steroidal anti-inflammatory drugs (NSAIDs) have been researched for their capacity to reduce cancer incidence, primarily due to their COX-2 inhibition properties. However, concerns have arisen regarding the precision of their targeting abilities. Nanoparticle approaches are revolutionizing cancer treatment by enabling targeted drug delivery, which enhances the efficacy and reduces the toxicity of chemotherapy. Particularly, chitosan-based nanoparticles are noteworthy for their biocompatibility, biodegradability, and ability to improve drug delivery. In this study, we synthesized folic acid-conjugated, 1,5-diaryl pyrazole-loaded chitosan (FA-CS-DP) nanoparticles using the ionic gelation method. The bioavailability and anti-neoplastic effects in a 7,12-dimethylbenzanthracene (DMBA)-exposed zebrafish model was investigated. MTT assay showed dose-dependent cytotoxicity of FA-CS-DP nanoparticles against MCF-7 breast cancer. The nanoparticles showed no toxicity to zebrafish embryos up to 100 μg/mL. The nanoparticle reduced oxidative stress and enhanced apoptosis in zebrafish exposed to DMBA. The morphological examination suggests that tumor growth was prevented in the zebrafish's surface and internal regions. The gene expression analysis confirmed the decrease in the expression of anti-inflammatory genes, such as cox-2 and nf-κb, and apoptosis inhibitor genes, such as bcl-2 and mdm2. By regulating the anti-inflammatory and apoptosis inhibitor genes, FA-CS-DP nanoparticle prevents neoplastic growth in the zebrafish model.

Hyperthermia reduces cancer cell invasion and combats chemoresistance and immune evasion in human bladder cancer.

Bladder cancer (BC) is a common malignancy and its most prevalent type is urothelial carcinoma, which accounts for ~90% of all cases of BC. The current treatment options for BC are limited, which necessitates the development of alternative treatment strategies. Hyperthermia (HT), as an adjuvant cancer therapy, is known to improve the efficacy of chemotherapy or radiotherapy. The present study aimed to investigate the anti‑tumor effects of HT on cell survival, invasiveness, chemoresistance and immune evasion in human BC cell lines (5637, T24 and UMUC3). Calcein AM staining was performed to analyze the cytotoxicity of natural killer (NK) cells against human BC cells following HT treatment. Cell migration and invasion affected by HT were analyzed using Transwell migration and invasion assays. It was found that HT inhibited the proliferation of BC cells by downregulating the phosphorylation of protein kinase B. Moreover, HT effectively enhanced the sensitivity of BC cells to the chemotherapy drug cisplatin (DDP) and reduced the chemoresistance of DDP‑resistant cells by downregulating the expression of cadherin‑11. It was further demonstrated that HT inhibited the migration and invasion of BC cells and enhanced the cytotoxic effects of NK cells. In summary, the antineoplastic effects of HT were mediated through three main mechanisms: Enhancement of the chemosensitivity of BC cells and mitigation of DDP‑induced chemoresistance, suppression of the invasive potential of BC cells and reinforcement of the anticancer response of NK cells. Thus, HT appears to be a promising adjunctive therapy for human BC.

Three Birds with One Stone: Copper Ions Assisted Synergistic Cuproptosis/Chemodynamic/Photothermal Therapy by a Three-Pronged Approach.

Copper is indispensable to organisms, while its homeostatic imbalance may interference normal cellular physiological processes and even induce cell death. Artificially regulating cellular copper content provides a viable strategy to activate antineoplastic effect. In light of this, a copper ions homeostasis perturbator (CuP-CL) with cinnamaldehyde (Cin) packaging and thermosensitive liposome coating is reported. Following laser exposure, the doping of Cu2+ in polydopamine initiates enhanced photothermal therapy (PTT) and unlocks the outer layer of liposome, leading to the release of copper ions and Cin in tumor microenvironment with mild acidity and high glutathione (GSH) levels. The liberative Cu2+ can evoke cuproptosis and chemodynamic therapy (CDT). Meanwhile, leveraging the merits of H2O2 supply and GSH consumption, Cin serves as a tumor microenvironment regulator to amplify Cu2+ mediated cuproptosis and CDT. Additionally, the positive feedback effects of "laser-triggered PTT, PTT accelerates reactive oxygen species (ROS) generation, ROS amplifies lipid peroxide (LPO) accumulation, LPO mediates heat shock proteins (HSPs) clearance, down-regulated HSPs promote PTT" entailed the overall benefit to therapeutic outcomes. Both in vitro and in vivo results corroborate the remarkable antineoplastic performance of CuP-CL by the synergy of cuproptosis/CDT/PTT. Collectively, based on the three-pronged approach, this work plots a viable multimodal regimen for cancer therapy.