Anticancer Effects Research Articles

Piperine inhibits the proliferation of colorectal adenocarcinoma by regulating ARL3-mediated endoplasmic reticulum stress.

Colorectal adenocarcinoma (COAD) is a significant cause of cancer-related mortality worldwide, necessitating the identification of novel therapeutic targets and treatments. This research aimed to investigate the role of ARL3 in COAD progression and to explore the effects of Piperine on ARL3 expression, cell proliferation, epithelial-mesenchymal transition (EMT), and endoplasmic reticulum (ER) stress. Bioinformatics analysis of The Cancer Genome Atlas (TCGA)-COAD, GSE39582, and GSE44861 datasets assessed ARL3 expression levels. Immunohistochemical data from the Human Protein Atlas (HPA) database confirmed ARL3 overexpression in COAD. The association of ARL3 with COAD clinical parameters and prognosis was also examined. COAD cells were treated with Piperine, and in vitro assays evaluated cell proliferation, apoptosis, EMT marker expression, and ER stress responses. ARL3 overexpression in COAD correlated with poor prognosis and varied across pathological stages. Piperine treatment inhibited COAD cell proliferation in a concentration- and time-dependent manner, as indicated by reduced Ki-67 levels and decreased colony-forming ability. Piperine induced S-phase cell cycle arrest and facilitated apoptosis in COAD cells, evidenced by changes in Bax, Bcl-2, cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase (PARP) levels. Moreover, Piperine downregulated ARL3 expression in COAD cells, thereby suppressing transforming growth factor beta (TGF-β)-induced EMT. Additionally, Piperine attenuated the ARL3-mediated ER stress response, significantly reducing binding immunoglobulin protein (BiP), inositol-requiring enzyme 1 alpha (p-IRE1α), activating transcription factor 6 (ATF6), and C/EBP homologousprotein (CHOP) levels. Piperine exerted anti-cancer effects in COAD by modulating ARL3 expression, disrupting cell cycle progression, inhibiting the EMT pathway, and regulating ER stress. These findings suggest that Piperine holds promise as a therapeutic agent for COAD through its targeting of ARL3.

Investigating the Anticancer Effects of Pleurotus Ostreatus Polysaccharide on G0/G1 Cell Cycle Arrest and Apoptosis in Ehrlich Ascites Carcinoma Cells.

Cancer is one of the leading causes of mortality worldwide. Despite the advancement of cancer treatment by various means including surgery, chemotherapy, etc., cancer is still a challenging disease to manage. This study was undertaken to investigate extraction, purification, structural elucidation, and the potential anti-cancer effects of Pleurotus ostreatuspolysaccharide (POP). The anti-cancer activities were performed on the Ehrlich Ascites Carcinoma Cell Line. The results demonstrated that the MW of POP was154649.8 Da with homopolysaccharide composed of D-glucose units, featuring (1→6)-α-D-Glcp backbone with O-6 branches and T-α-D-Glcp terminations. and the yield was 6.27%. was 6.27%, The antitumor activity assessment demonstrated significant cytotoxicity of POP against Ehrlich Ascites Carcinoma (EAC) cells, with an IC50 of 121.801 µg/mL, supported by LDH release analysis. POP inhibited cell migration, invasion, and colony formation, indicating its potential as an anti-cancer agent. POP elicited the apoptotic activity with the upregulation of Caspase-9 and Bax, and downregulation of Bcl-2. The DNA fragmentation assay further confirmed apoptosis-mediated DNA degradations. Additionally, POP-induced cell cycle arrest at the G0/G1 phase, by altering the expression of p53, Cyclin D, and Cdk4 proteins.So, Pleurotus ostreatus polysaccharide (POP) showedsignificant cytotoxicity on Ehrlich Ascites Carcinoma cells, indicating potential as an anti-cancer agent.

Enhanced anticancer activity of silver doped zinc oxide magnetic nanocarrier loaded with sorafenib for hepatocellular carcinoma treatment

Drug delivery is the process or method of delivering a pharmacological product to have therapeutic effects on humans or animals. The use of nanoparticles to deliver medications to cells is driving the present surge in interest in improving human health. Green nanodrug delivery methods are based on chemical processes that are acceptable for the environment or that use natural biomaterials such as plant extracts and microorganisms. In this study, zinc oxide-superparamagnetic iron oxide-silver nanocomposite was synthesized via green synthesis method using Fusarium oxysporum fungi mycelia then loaded with sorafenib drug. The synthesized nanocomposites were characterized by UV-visibile spectroscopy, FTIR, TEM and SEM techniques. Sorafenib is a cancer treatment and is also known by its brand name, Nexavar. Sorafenib is the only systemic medication available in the world to treat hepatocellular carcinoma. Sorafenib, like many other chemotherapeutics, has side effects that restrict its effectiveness, including toxicity, nausea, mucositis, hypertension, alopecia, and hand-foot skin reaction. In our study, 40 male albino rats were given a single dose of diethyl nitrosamine (DEN) 60 mg/kg b.wt., followed by carbon tetrachloride 2 ml/kg b.wt. twice a week for one month. The aim of our study is using the zinc oxide-superparamagnetic iron oxide-silver nanocomposite that was synthesized by Fusarium oxysporum fungi mycelia as nanocarrier for enhancement the sorafenib anticancer effect.

Antibody-Decorated Nanoplatform to Reprogram Macrophage and Block Immune Checkpoint LSECtin for Effective Cancer Immunotherapy.

Repolarizing tumor-associated macrophages (TAMs) into tumor-inhibiting M1 macrophages has been considered a promising strategy for enhanced cancer immunotherapy. However, several immunosuppressive ligands (e.g., LSECtin) can still be highly expressed on M1 macrophages, inducing unsatisfactory therapeutic outcomes. We herein developed an antibody-decorated nanoplatform composed of PEGylated iron oxide nanoparticles (IONPs) and LSECtin antibody conjugated onto the surface of IONPs via the hydrazone bond for enhanced cancer immunotherapy. After intravenous administration, the tumor microenvironment (TME) pH could trigger the hydrazone bond breakage and induce the disassociation of the nanoplatform into free LSECtin antibodies and IONPs. Consequently, the IONPs could repolarize TAMs into M1 macrophages to remodel immunosuppressive TME and provide an additional anticancer effect via secreting tumoricidal factors (e.g., interlukin-12). Meanwhile, the LSECtin antibody could further block the activity of LSECtin expressed on M1 macrophages and relieve its immunosuppressive effect on CD8+ T cells, ultimately leading to significant inhibition of tumor growth.

KLHL21 suppresses gastric tumourigenesis via maintaining STAT3 signalling equilibrium in stomach homoeostasis

ObjectivePrecancerous metaplasia transition to dysplasia poses a risk for subsequent intestinal-type gastric adenocarcinoma. However, the molecular basis underlying the transformation from metaplastic to cancerous cells remains poorly understood.DesignAn integrated analysis...

Erdafitinib Promotes Ferroptosis in Human Uveal Melanoma by Inducing Ferritinophagy and Lysosome Biogenesis via Modulating the FGFR1/mTORC1/TFEB Signaling Axis

Uveal melanoma (UM) is a rare yet lethal primary intraocular malignancy affecting adults. Analysis of data from The Cancer Genome Atlas (TCGA) database revealed that FGFR1 expression was increased in UM tumor tissues and was linked to aggressive behavior and a poor prognosis. This study assessed the anti-tumor effects of Erdafitinib, a selective pan-FGFR inhibitor, in both in vitro and in vivo UM models. Erdafitinib exhibited a robust anti-cancer activity in UM through inducing ferroptosis in the FGFR1-dependent manner. Transcriptomic data revealed that Erdafitinib mediated its anti-cancer effects via modulating the ferritinophagy/lysosome biogenesis. Subsequent research revealed that Erdafitinib exerted its effects by reducing the expression of FGFR1 and inhibiting the activity of mTORC1 in UM cells. Concurrently, it enhanced the dephosphorylation, nuclear translocation, and transcriptional activity of TFEB. The aggregation of TFEB in nucleus triggered FTH1-dependent ferritinophagy, leading to lysosomal activation and iron overload. Conversely, the overexpression of FGFR1 served to mitigate the effects of Erdafitinib on ferritinophagy, lysosome biogenesis, and the activation of the mTORC1/TFEB signaling pathway. In vivo experiments have convincingly shown that Erdafitinib markedly curtails tumor growth in an UM xenograft mouse model, an effect that is closely correlated with a decrease in FGFR1 expression levels. The present study is the first to demonstrate that Erdafitinib powerfully induces ferroptosis in UM by orchestrating the ferritinophagy and lysosome biogenesis via modulating the FGFR1/mTORC1/TFEB signaling. Consequently, Erdafitinib emerges as a strong candidate for clinical trial investigation, and FGFR1 emerges as a novel and promising therapeutic target in the treatment of UM.

In vitro study on the anticancer effects of oxalipalladium against PC3 human prostate carcinoma cells

Prostate cancer is a common type of cancer in men with high incidence and mortality. Our aim was to investigate the effects of oxalipalladium (ox-Pd) on metastatic human prostate cancer PC3 cells and compare them with the effects of oxaliplatin (ox-Pt) (as an approved cancer drug). We synthesized ox-Pd through a new chemical method and used FT-IR, 1H NMR, 13C NMR, and MS analyzes to characterize it. The effects of ox-Pd on PC3 cells viability, apoptosis, cell cycle, migration, and gene expression were examined. Inhibition of topoisomerase IIα activity was investigated by pHOT1 plasmid relaxation and kDNA decatenation assays. Chemical tests showed ox-Pd with the correct composition and structure. For the first time, the exact fragmentation pathway of ox-Pd and its difference with ox-Pt was obtained by MS analysis. Ox-Pd significantly decreased PC3 cell viability with less/no toxicity effect on MHFB-1 normal skin fibroblasts. Wound scratch assay confirmed the strong anti-migratory activity of ox-Pd. According to flow cytometry analysis, this drug increased the number of PC3 cells in late apoptosis and decreased DNA replication and mitosis. Furthermore, pHOT1 plasmid relaxation and kDNA decatenation assays showed that ox-Pd strongly inhibited the catalytic activity of topoisomerase IIα. The expression of topoisomerase IIα, Bcl-2, P21, and survivin was decreased while the expression of Bax and p53 was increased under ox-Pd treatment. We provide the first evidence that ox-Pd exhibits more selective anticancer effects on PC3 cells compared to ox-Pt. Taken together, these data strongly suggest a therapeutic window for ox-Pd in cancer.

Long Noncoding RNA CRNDE Promotes Gastric Cancer Progression through Targeting miR-136-5p/MIEN1.

Background: Long noncoding RNAs (lncRNAs) contribute to the initiation and progression of gastric cancer (GC). The purpose of this study is to examine the potential role of lncRNA colorectal neoplasia differentially expressed (CRNDE)in modulating the expression of migration and invasion enhancer 1 (MIEN1) through the suppression of miR-136-5p in GC. Methods: The biological roles of CRNDE, miR-136-5p, and MIEN1 in GC were assessed both in laboratory settings and through the examination of clinical samples. Results: CRNDEwas found to be significantly increased in GC tissues, and this upregulation was associated with an unfavorable prognosis of GC patients. In vitro experiments showed that inhibiting cell growth and migration, along with promoting apoptosis in GC cells, could be achieved by either disabling CRNDEor MIEN1, or by increasing the expression of miR-136-5p. MIEN1 is a specific recipient of miR-136-5p, and the anticancer effects of miR-136-5p can be counteracted by the increased expression of MIEN1. Through the examination of clinical specimens, it has been observed that there is a significant positive correlation between the expression of MIEN1 and CRNDE. In contrast, miR-136-5p expression in GC tissues shows a negative correlation. Conclusion: A previously unexplored therapeutic target for GC involves the CRNDE/miR-136-5p/MIEN1 signal transduction cascade.

Selective anticancer effects of plasma-activated saline in 3D tumor model co-culturing of normal cells and cancer cells

Selective anticancer effects of plasma-activated saline in 3D tumor model co-culturing of normal cells and cancer cells

Phytochemical-mediated modulation of autophagy and endoplasmic reticulum stress as a cancer therapeutic approach.

Autophagy and endoplasmic reticulum (ER) stress are conserved processes that generally promote survival, but can induce cell death when physiological thresholds are crossed. The pro-survival aspects of these processes are exploited by cancer cells for tumor development and progression. Therefore, anticancer drugs targeting autophagy or ER stress to induce cell death and/or block the pro-survival aspects are being investigated extensively. Consistently, several phytochemicals have been reported to exert their anticancer effects by modulating autophagy and/or ER stress. Various phytochemicals (e.g., celastrol, curcumin, emodin, resveratrol, among others) activate the unfolded protein response to induce ER stress-mediated apoptosis through different pathways. Similarly, various phytochemicals induce autophagy through different mechanisms (namely mechanistic target of Rapamycin [mTOR] inhibition). However, phytochemical-induced autophagy can function either as a cytoprotective mechanism or as programmed cell death type II. Interestingly, at times, the same phytochemical (e.g., 6-gingerol, emodin, shikonin, among others) can induce cytoprotective autophagy or programmed cell death type II depending on cellular contexts, such as cancer type. Although there is well-documented mechanistic interplay between autophagy and ER stress, only a one-way modulation was noted with some phytochemicals (carnosol, capsaicin, cryptotanshinone, guangsangon E, kaempferol, and δ-tocotrienol): ER stress-dependent autophagy. Plant extracts are sources of potent phytochemicals and while numerous phytochemicals have been investigated in preclinical and clinical studies, the search for novel phytochemicals with anticancer effects is ongoing from plant extracts used in traditional medicine (e.g., Origanum majorana). Nonetheless, the clinical translation of phytochemicals, a promising avenue for cancer therapeutics, is hindered by several limitations that need to be addressed in future studies.

The Recent Development of Luteolin-loaded Nanocarrier in Targeting Cancer.

Luteolin (LUT), a naturally occurring flavonoid found in vegetables, fruits, and herbal medicines, has been extensively studied for its pharmacological activities, including anti-proliferative and anticancer effects on various cancer lines. It also exhibits potent antioxidant properties and pro-apoptotic activities against human cancers. However, its therapeutic potential is hindered by its poor solubility in water (5 μg/ml at 45°C) and low bioavailability. This research on the development of luteolin-loaded nanocarrier aims to overcome these limitations, thereby opening up new possibilities in cancer treatment. This paper covers several nanoformulations studied to increase the solubility and bioavailability of LUT. The physicochemical characteristics of the nanoformulation that influence luteolin's solubility and bioavailability have been the subject of more in-depth investigation. Furthermore, it examines how LUT's anti-inflammatory and antioxidant properties aid in lessening the side effects of chemotherapy. Most nanoformulations, including phytosomes, lipid nanoparticles, liposomes, protein nanoparticles, polymer micelles, nanoemulsions, and metal nanoparticles, have shown promising results in improving the solubility and bioavailability of LUT. This is a significant step forward in enhancing the therapeutic potential of LUT in cancer treatment. Furthermore, the study found that LUT's ability to scavenge free radicals can significantly reduce the side effects of cancer treatment, further highlighting its potential to improve patient outcomes. Nanoformulations, because of their unique surface and physiochemical properties, improve the solubility and bioavailability of LUT. However, poor in-vitro and in-vivo correlation and scalability of nanoformulations need to be addressed to achieve good clinical performance of LUT in oncology.

Assessing the antioxidant properties of Naringin and Rutin and investigating their oxidative DNA damage effects in breast cancer

This work examines the capacity of Naringin and Rutin to influence the DNA damage response (DDR) pathway by investigating their interactions with key DDR proteins, including PARP-1, ATM, ATR, CHK1, and WEE1. Through a combination of in silico molecular docking and in vitro evaluations, we investigated the cytotoxic and genotoxic effects of these compounds on MDA-MB-231 cells, comparing them to normal human fibroblast cells (2DD) and quiescent fibroblast cells (QFC). The research found that Naringin and Rutin had strong affinities for DDR pathway proteins, indicating their capacity to specifically regulate DDR pathways in cancer cells. Both compounds exhibited preferential cytotoxicity towards cancer cells while preserving the vitality of normal 2DD fibroblast cells, as demonstrated by cytotoxicity experiments conducted at a dose of 10 µM. The comet experiments performed particularly on QFC cells provide valuable information on the genotoxic impact of Naringin and Rutin, highlighting the targeted initiation of DNA damage in cancer cells. The need to use precise cell models to appropriately evaluate toxicity and genotoxicity is emphasized by this discrepancy. In addition, ADMET and drug-likeness investigations have emphasized the pharmacological potential of these compounds; however, they have also pointed out the necessity for optimization to improve their therapeutic profiles. The antioxidant capabilities of Naringin and Rutin were assessed using DPPH and free radical scavenging assays at a concentration of 10 µM. The results confirmed that both compounds have a role in reducing oxidative stress, hence enhancing their anticancer effects. Overall, Naringin and Rutin show potential as medicines for modulating the DDR in cancer treatment. They exhibit selective toxicity towards cancer cells while sparing normal cells and possess strong antioxidant properties. This analysis enhances our understanding of the therapeutic uses of natural chemicals in cancer treatment, supporting the need for more research on their mechanisms of action and clinical effectiveness.

Molecular pathway of anticancer effect of next-generation HSP90 inhibitors XL-888 and Debio0932 in neuroblastoma cell line

Neuroblastoma is a common nervous system tumor in childhood, and current treatments are not adequate. HSP90 is a molecular chaperone protein that plays a critical role in the regulation of cancer-related proteins. HSP90 inhibition may exert anticancer effects by targeting cancer-related processes such as tumor growth, cell proliferation, metastasis, and apoptosis. Therefore, HSP90 inhibition is a promising strategy in the treatment of various types of cancer, and the development of next-generation inhibitors could potentially lead to more effective and safer treatments. XL-888 and Debio0932 is a next-generation HSP90 inhibitor and can inhibit the correct folding and stabilization of client proteins that cancer-associated HSP90 helps to fold correctly. In this study, we aimed to investigate the comprehensive molecular pathways of the anticancer activity of XL-888 and Debio0932 in human neuroblastoma cells SH-SY5Y. The cytotoxic effects of XL-888 and Debio0932 on the neuroblastoma cell line SH-SY5Y cells were evaluated by MTT assay. Then, the effect of these HSP90 inhibitors on the expression of important genes in cancer was revealed by Quantitative Real Time Polymerase Chain Reaction (qRT-PCR) method. The qRT-PCR data were evaluated using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) biological process tools. Finally, the effect of HSP90 inhibitors on HSP27, HSP70 and HSP90 protein expression was investigated by Western blotting analysis. The results revealed that XL-888 and Debio0932 had a role in regulating many cancer-related pathways such as migration, invasion, metastasis, angiogenesis, and apoptosis in SH-SY5Y cells. In conclusion, it shows that HSP90 inhibitors can be considered as a promising candidate in the treatment of neuroblastoma and resistance to chemotherapy.

P-373 Melatonin and chemotherapy: does the proposed fertoprotective agent impair the anti-tumor effects of cancer therapy?

Abstract Study question Does the proposed fertoprotective agent melatonin interfere with the anti-cancer activity of imatinib chemotherapy in a chronic myelogenous leukemia (CML) cell line? Summary answer At low concentrations, melatonin demonstrates mild inhibition of imatinib activity, however this is overcome at therapeutic concentrations. Melatonin also shows anti-tumor activity against CML. What is known already A harmful consequence of cancer therapy is a resultant loss of fertility. Pharmacologic interventions that reduce radiation or chemotherapy-induced gonadotoxicity are a major unmet medical need. Several ‘fertoprotective’ agents have shown promise in protecting the gonads from injury during treatment, including melatonin. However, melatonin is not currently applied in humans for this purpose. Key safety and efficacy data are needed to move potential fertoprotective agents into clinical trials. Study design, size, duration We evaluated the interaction of varying combined concentrations of melatonin and imatinib, a tyrosine kinase inhibitor, within an in-vitro matrix experiment. The interaction was be evaluated within K562, a cell line derived from human chronic myelogenous leukemia (CML). This chemotherapy and cell line were selected due to CML’s dependence on BCR-ABL for survival, which is inhibited by imatinib, permitting direct evaluation of melatonin-imatinib cross-interaction. Participants/materials, setting, methods K562 were seeded in 384-well plates into which increasing concentrations of imantinib and melatonin were progressively dispensed. The cells were cultured for 48 hours. Viable cell concentrations were then determined using a cell luminescent assay. Drug interaction was then determined using drug synergy analysis software.The expected drug combination responses were calculated based on ZIP reference model using SynergyFinder 3.0. Deviations between observed and expected responses with positive and negative values denote synergy and antagonism respectively. Main results and the role of chance Melatonin demonstrated toxicity to K562 CML cell lines independent of imatinib, with a mean inhibition of cell growth of 74.7% at 1uM, CI [69.6%, 79.7%]. This anti-tumor activity was progressively seen at concentrations >0.1 uM. At low imatinib concentrations (<0.2 uM), melatonin decreased the anti-cancer potency of imatinib. This effect was overcome at higher concentrations of imatinib. The overall mean synergy score was -5.87, CI [-7.145, -4.588]. Limitations, reasons for caution These experiments were carried out in an in-vitro setting in a tightly controlled environment. In a clinical setting, the complexity of potential interactions between melatonin and chemotherapy will increase (i.e. metabolism, distribution), thus animal models will be a necessary next step of evaluation before clinical safety trials may proceed. Wider implications of the findings Melatonin may serve as an inexpensive, well-tolerated adjuvant to help protect the gonad from chemotherapy, while additionally exhibiting its own anti-cancer effects in certain settings. Our preliminary data suggests that the risk of melatonin to impair active imatinib treatment may be low, however continued investigation is necessary. Trial registration number Not applicable

Exploring Bioactive Compounds in Underutilized Fruit Crops of Arid and Semi-Arid Regions: A Comprehensive Review

Exploring the bioactive compounds in underutilized fruit crops of arid regions reveals a wealth of phytochemicals, including polyphenols, vitamins, polyunsaturated fatty acids, amino acids, and carotenoids. These compounds exhibit significant health benefits, evidenced through both in vitro and in vivo studies, demonstrating antioxidant, anti-inflammatory, antimicrobial, hypolipidemic and neuroactive properties. This review delves into the bioactive compounds found in fruits of arid and semi-arid regions, highlighting their phytochemical compositions and their potential in preventing chronic diseases, thereby enhancing human health. Underutilized fruit crops, typically grown and consumed locally rather than being commercially cultivated or widely traded, offer several advantages. They are easier to grow, more resilient to climate change, and exceptionally rich in phytochemicals with medicinal properties. These fruits, such as Indian jujube, Indian gooseberry, bael, and tamarind, among others, are valuable for their high nutritional content and potential to meet the dietary needs of rural populations in arid regions. Local knowledge attests to their nutritional and medicinal benefits, necessitating rigorous study for conservation and nutritional characterization to broaden future food options and enhance functional and nutritional values. This review outlines the ethnobotany, medicinal and nutritional values, biodiversity conservation, and utilization strategies for significant underutilized fruit crops from arid and semi-arid regions. These fruits are rich in diverse phytochemical compounds like flavonoids, tannins, terpenoids, saponins, glycosides, and alkaloids, which are utilized to treat various health conditions in humans and livestock. Their extracts demonstrate a range of activities, including antipyretic, analgesic, anti-inflammatory, anticancer, antimicrobial, antiplasmodial and antinociceptive effects. Highlighting the current research on the nutritional profiling, chemical composition, and potential applications of these fruits, this chapter addresses the knowledge gap concerning the health benefits of consuming arid and semi-arid fruits. This is particularly relevant given the growing interest in "superfoods" and the need for evidence-based public health guidelines to inform consumers about the benefits of polyphenol-rich plant foods in preventing chronic diseases such as cardiovascular disease and cancer.

Characterization and anticancer evaluation of zirconia nanoparticles synthesized via green route using sophora flavescens roots extract

The emergence of drug resistance in cancer cells has impeded recent progress in cancer therapy, leading to the investigation of novel anticancer drugs. The fabrication of metal and ZrO2 nanoparticles is a promising path with prospective applications across diverse technological domains. The present study investigates the potential anticancer effects of ZrO2 NPs obtained from the root extract of Sophora flavescens on MCF-7 breast cancer cells. The structural and chemical features of these nanoparticles are analyzed using several techniques such as flow cytometry, SEM, TEM, FTIR, and UV–vis spectroscopy. The examination of XRD and TEM images demonstrates the significant contribution of plant root extract in enhancing the efficiency of nanoparticles, leading to the formation of nearly tetragonal crystal structures with an average size of 8 nm. The MTT experiment verifies the nanoparticles' anticancer activity, which depends on the dosage. The IC50 value of 253 μg/mL indicates the half-maximal inhibitory concentration. The optical microscope reveals an unusual sight: MCF-7 cells appear more spherical and less dense at higher concentrations. This research also investigates the antibacterial properties of ZrO2 nanoparticles against harmful bacteria, particularly those resistant to multiple drugs. The diffusion disk assay indicates that the nanoparticles are active against drug-resistant isolates, with zones of inhibition ranging from 31 to 55 millimeters. Additionally, the researchers noted a positive correlation between nanoparticle concentration and the size of the inhibition zone. Overall, the data indicates the potential of ZrO2 NPs to aid in cancer therapy as well as in combating infections.

Molecular Evidence of the Bio-activities of Traditional Home Medicine Ingredients.

For many centuries, traditional medicine has played an essential role in health care. The treatment of many illnesses, including cancer, has greatly benefited from using herbal remedies derived from traditional medicine. The bioactive compounds, such as curcumin, silibinin, berberine, ginseng, and others present in traditional medicine have shown a wide range of properties, such as anti-inflammatory, antimicrobial, anti-oxidant as well as potent anti-cancer properties both in laboratory studies and animal experiments (in vitro and in vivo). In this review, we mainly emphasized the anticancer role of bioactive compounds present in traditional medicine, such as curcumin, cardamonin, piperine, berberine, ginseng, silibinin, epigallocatechin gallate, and asafoetida. We also discussed molecular evidence of these compounds in chemoprevention and anticancer effects. These compounds have the potential to interfere with cancer growth, proliferation, metastasis, and angiogenesis and induce apoptosis by targeting different pathways and the cell cycle. This review article also focuses on how these compounds can help overcome drug resistance and enhance the availability of other clinically approved drugs. The usage of these compounds synergistically with other forms of treatment is also of great fascination to new and upcoming research. Finally, we have discussed the bioavailability of these compounds and strategies employed to improve them so their full potential can be exploited.

An optimal combination of four active components in Huangqin decoction for the synergistic sensitization of irinotecan against colorectal cancer

BackgroundIrinotecan (CPT-11) is a first-line treatment for advanced colorectal cancer (CRC). Four components (baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from Huangqin Decoction (HQD) have been proven to enhance the anticancer activity of CPT-11 in our previous study.ObjectiveThis study aimed to determine the optimal combination of the four components for sensitizing CPT-11 as well as to explore the underlying mechanism.MethodsThe orthogonal design method was applied to obtain candidate combinations (Cmb1-9) of the four components. The influence of different combinations on the anticancer effect of CPT-11 was first evaluated in vitro by cell viability, wound healing ability, cloning formation, apoptosis, and cell cycle arrest. Then, a CRC xenograft mice model was constructed to evaluate the anticancer effect of the optimal combination in vivo. Potential mechanisms of the optimal combination exerting a sensitization effect combined with CPT-11 against CRC were analyzed by targeted metabolomics.ResultsIn vitro experiments determined that Cmb8 comprised of baicalin, baicalein, wogonin, and glycyrrhizic acid at the concentrations of 17 μM, 47 μM, 46.5 μM and 9.8 μM respectively was the most effective combination. Importantly, the cell viability assay showed that Cmb8 exhibited synergistic anticancer activity in combination with CPT-11. In in vivo experiments, this combination (15 mg/kg of baicalin, 24 mg/kg of baicalein, 24 mg/kg of wogonin, and 15 mg/kg of glycyrrhizic acid) also showed a synergistic anticancer effect. Meanwhile, inflammatory factors and pathological examination of the colon showed that Cmb8 could alleviate the gastrointestinal damage induced by CPT-11. Metabolic profiling of the tumors suggested that the synergistic anticancer effect of Cmb8 might be related to the regulation of fatty acid metabolism.ConclusionThe optimal combination of four components derived from HQD for the synergistic sensitization of CPT-11 against CRC was identified.

Synergistic Antitumor and Apoptotic Activity of Sitagliptin or Linagliptin Plus Cisplatin Against A549 Lung Cancer Cells (an Invitro Study)

Objective: Lung cancer (LC) has the highest mortality rate globally. Most chemotherapeutic medicines now in use are cytotoxic, prompting the search for novel compounds with anticancer properties and improved safety profiles for normal cells. Dipeptidyl peptidase-4 inhibitors have demonstrated anticancer effects and apoptotic properties by specifically inhibiting dipeptidyl peptidase -4, a glycoprotein found in various organs that support the spread of cancer and tumor formation. Based on that, this study aimed to evaluate the cytotoxicity and apoptotic activity of sitagliptin (SITA) and linagliptin (LINA) against the lung cancer cell line (A549) alone and in combination with cisplatin (CP). Methods: A549 cells were categorized into six groups: control (untreated cells), CP-treated cells, SITA-treated cells, LINA-treated cells, CP plus SITA treated cells (1:1 ratio), and CP plus LINA treated cells (1:1 ratio). After 72 hours of incubation, cell viability (or cytotoxicity) and concentration required to inhibit 50% of cell viability (IC50) for each group were determined using an MTT assay. This method is safe and easy to use, has more reproducibility, and is commonly used for cell viability and cytotoxicity tests. Later, A549 cells were cultured in six flasks and exposed to the IC50 for 36 hours. Afterward, the cells were harvested and centrifuged, and the supernatant was removed. The remaining cell pellets were collected and lysed using a lysis buffer to measure B-cell lymphoma type 2 (BCL-2) levels with ELISA test kits. The data was collected and subjected to statistical analysis techniques. Results: MTT assay results determined that SITA and LINA significantly increased A549 cell cytotoxicity compared to the control group (P<0.0001). Moreover, combining SITA or LINA with CP showed markedly increased antitumor efficacy and more significant cytotoxicity directed toward A549 cells. Additionally, these combinations highly reduced IC50 in comparison to monotherapy. Considerably, both drugs showed remarkable apoptotic activity on A549 cells when used alone or combined with CP by decreasing BCL2 levels. Consequently, it potentiates apoptotic effects and cytotoxicity of CP against cancer cells. Interestingly, Lina was more potent than Sita regarding cytotoxicity and apoptotic activity on A549 cells. Conclusion: SITA and Lina exhibited significant cytotoxic and apoptotic effects against A549 cells through the induction of apoptosis. Notably, the results suggest a potential synergistic anticancer impact on CP.

Moringa oleifera seed methanol extract with consolidated antimicrobial, antioxidant, anti-inflammatory, and anticancer activities.

The wide biological activity of the Moringa oleifera represents a potential opportunity for developing selective cancer treatment drugs. The bioactive phytochemicals in Moringa seed extract (MSE) indicated large numbers of phytochemicals (21 compounds) with dominant abundance for cycloisolongifolene, 8,9-dehydro-9-vinyl, and chamazulene accounting for 12.7% and 12.19% of the total detected compounds. The MSE showed a potent anticancer effect toward Caco-2, MDA, and HepG-2 cells with half-maximal inhibitory concentration (IC50) values of 9.15±1.18, 4.85±0.11, and 7.36±0.22µg/mL, respectively, with higher safety (≥31-folds) toward normal human cells (IC50 of 150.7±11.11µg/mL). It appears that MSE stimulates selective-dose-dependent cell shrinkage, and nuclear condensation in the tumor cells, which finally induces the apoptosis pathway to increase its anticancer action. Additionally, MSE showed a potent capability to stimulate cell cycle arrest in both main checkpoint phases (G0/G1 and G2/M) of cell population growth. The apoptotic death stimulation was confirmed through upregulation of tumor protein p53 (p53) and cyclin-dependent kinase inhibitor p21 (p21) expression by more than three- to sixfold and downregulation of B-cell lymphoma 2 expression (threefold) in MSE-treated cells compared to 5-fluorouracil (5-FU)-treated tumor cells. Furthermore, the MSE revealed strong anti-inflammatory activity with significant antioxidant activity by lowering nitric oxide levels and enhancing the superoxide dismutase activity. On the other hand, the MSE revealed broad-spectrum antibacterial activity in a dose-dependent manner against Staphylococcus aureus minimum inhibitory concentration (MIC of 1.25mg/mL), followed by Salmonella typhimurium (MIC of 1.23mg/mL), whereas Escherichia coli was the least sensitive to MSE activity (MIC of 22.5mg/mL) with significant antibiofilm activity against sensitive pathogens.