Anticancer Research Articles

Flavonoid-metal ion Complexes as Potent Anticancer metallodrugs: A comprehensive Review.

Flavonoids and their analogous are mainly found in pink lady apples, green and black tea (catechins), celery and red peppers, onions, broccoli and spinach, berries, cherries, soybean, citrus fruits, and fungi. The different derivatives of flavonoids belonging to polyphenolic compounds such as 3,4',5,7-Tetrahydroxyflavylium (pelargonidin), 2-(3,4-Dihydroxyphenyl)chromenylium-3,5,7-triol (cyanidin), 3,3',4',5,5',7-Hexahydroxyflavylium (delphinidin), 3,3',4',5,7-Pentahydroxy-5'-methoxyflavylium (petunidin), and 3,4',5,7-Tetrahydroxy-3',5'-dimethoxyflavylium (malvidin) can act as good chelating agents for metal-chelate complex formation. These flavonoid-metal complexes have been reported to have various biomedical and pharmacological activities. Flavonoid-metal ion complexes display a broad spectrum of biological properties such as antioxidant, anti-inflammatory, anti-allergic, antiviral, anticarcinogenic, and cytotoxic activity. The literature survey showed that flavonoid metal complexes have potential therapeutic properties against various cancerous cells. The objective is to gain insight into the current perspective and development of novel anticancer metallodrug drugs. The flavonoid-metal ion complexes can be prepared by reacting flavonoid ligand with appropriate metal salt in aqueous or alcoholic reaction medium under stirring or refluxing conditions. In this review article, the various reported methods for the synthesis of flavonoid-metal complexes have been included. The utility of synthetic methods for flavonoid-metal complexes will support the discovery of novel therapeutic drugs. In this review study, short libraries of flavonoid-metal ion complexes were studied as potential anticancer agents against various human cancer cell lines. The review report reveals that metal ions such as Fe, Co, Ni, Cu, Zn, Rh, Ru, Ga, Ba, Sn etc., when binding to flavonoid ligands, enhance the anticancer activity compared to free ligands. This review study covered some important literature surveys for the last two decades. It has been concluded that flavonoid metal complexes have been associated with a wide range of biological properties that could be noteworthy in the medicinal field. Therefore, to develop a new anticancer drug, it is essential to determine the primordial interaction drug with DNA under physiological or anatomical conditions. The study of numerous flavonoid metal complexes mentioned in this paper could be the future treatment against various cancerous diseases.

List prices and clinical value of anticancer drugs in China, Japan, and South Korea: a retrospective comparative study

High prices of anticancer drugs have raised concerns due to their financial impact on patients and healthcare systems. This study aimed to assess the initial and latest list prices and clinical value of reimbursed anticancer drugs in China, Japan, and South Korea. We identified anticancer drugs newly approved by the National Medical Products Administration of China from January 2012 to June 2022, and by the Pharmaceuticals and Medical Devices Agency of Japan and the Ministry of Food and Drug Safety of South Korea up until June 2022. We compared initial and latest treatment prices between countries and assessed clinical value using patients' survival, quality of life (QoL), and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). We calculated Spearman rank correlation coefficients of treatment prices with clinical value for individual countries and employed regression analyses to investigate whether the relationship between prices and clinical value was modified by the country setting. Our cohort included 91 anticancer drug indications, with 60 listed for reimbursement in China, 91 in Japan, and 87 in South Korea. Median treatment prices were highest in Japan, followed by South Korea, and lowest in China, both for initial prices (US$64082 vs. US$45529 vs. US$19144, p<0.0001) and latest prices (US$50859 vs. US$31611 vs. US$18666, p<0.0001). Over time, China (β=-0.047, p<0.0001) and South Korea (β=-0.049, p<0.0001) witnessed more significant price reductions compared to Japan (β=-0.013, p=0.011). The correlations between both initial and latest treatment prices and clinical value (QoL and ESMO-MCBS) were more significant and stronger in China and South Korea than in Japan, although Japan exhibited slightly stronger correlations in terms of survival compared to China and South Korea. The relationship between clinical value and treatment prices may not be modified by the country setting. In comparison, South Korea's list prices and their correlations with clinical value appear reasonable. Policymakers in Japan could enhance efficiency by controlling prices and aligning them with clinical value, while China would need to take substantial steps to expand anticancer drug coverage. National Natural Science Foundation of China (72374149 and 72074163), and China Center for South Asian Studies, Sichuan University.

Clamp for Safety: Improving Intravesical Chemotherapy Practices.

Processes for intravesical chemotherapy after transurethral resection of nonmuscle invasive bladder tumors may lack standardization. In 2019, at a large health care system in Los Angeles, California, five incident reports involving chemotherapeutic agent spills from urinary catheters after bladder tumor procedures necessitated a quality improvement project. The project lead determined that a cost-effective alternative device for securing the chemotherapeutic agent in the bladder was needed at four surgical locations of the health care system. In addition, a review of the literature and an observational assessment revealed lack of adherence to standard and recommended processes for using personal protective equipment (PPE) when handling hazardous medications. After revising existing processes, acquiring a cost-effective clamp and recommended chemotherapy PPE, instructing personnel on the clamping process and use of PPE, and implementing use of the clamp, there have been no spills associated with intravesical chemotherapy across the four surgical locations.

Ethnopharmacological Survey of Medicinal Plants Used by Local Herbalists and Traditional Healers for the Treatment of Cancer in Jordan

Background: As many Jordanians include herbs in their treatment, an ethnopharmacological survey was conducted to identify the most prescribed plants for the treatment of cancer by local herbalists and traditional healers in Jordan, aiming to encourage the prescription that is based on scientific evidence, to tackle some important practices in traditional healing, and to provide candidates for the isolation of new anticancer agents. Methods: Thirty-two Jordanian herbalists and traditional healers were interviewed. Both the use value and frequency of citation were implemented as quantitative methods to demonstrate the relative importance of a chosen species for the treatment of cancer. Furthermore, literature was screened for evidences that supported or opposed the use of the plants of interest Results: It was revealed that 31 plants are currently used in Jordan for the treatment of cancer, with Curcuma longa and Ephedra foeminea being the most used ones. Conclusions: It was noticed that the use of many prescribed plants could be rationalised by in vitro and/or in vivo studies. However, more attention should be paid by practitioners to some important aspects, such as the method of use and preparation of plants, their interaction with chemotherapeutic agents and the differences in their efficacy against different cancer types.

Systemic hypertension with VEGFR inhibitor (axitinib) therapy in cancer patients: A meta-analysis and systematic review of randomized controlled trials

Vascular endothelial growth factor receptor inhibitors (VEGFRi), namely axitinib, are commonly used chemotherapeutic agents in patients with cancer; however, this medication has a significant cardiovascular side effect profile, such as high-grade hypertension. We performed this updated meta-analysis of RCTs to compile cardiovascular adverse events, such as all-grade and high-grade (>3) hypertension, the risk for thrombosis (DVT and PE), and peripheral edema. A systematic search was performed on PubMed, Cochrane, and Embase from inception until October 2023 for studies using axitinib to treat various cancers. Trials with patients randomly allocated for VEGFRi drug therapy with axitinib and reported all-grade hypertension as an outcome were included. Statistical analysis was performed using Cochrane Review Manager to calculate pooled proportions of odds ratios (OR) with a 95 % confidence interval (CI) using the random-effects model, Mantel−Haenszel method. A total of 8 RCTs and 2502 patients were included in the review. Compared with the placebo group, the VEGFRi (Axitinib) therapy group was associated with a higher risk of all-grade and high-grade hypertension, hand–foot syndrome, and fatigue. Furthermore, there was no increased risk of thromboembolism (DVT/PE) or hypothyroidism. However, a lower risk of peripheral edema was noted between the two groups. Screening for patients with preexisting hypertension, identifying risk factors for cardiovascular diseases before the initiation of VEGFRi therapy, and careful monitoring of high-risk patients during VEGFRi therapy, as well as prompt treatment with antihypertensive drugs, will help mitigate the adverse effects. Further evaluation using prospective designs is required to study the clinical significance and develop mitigation strategies.

Chemobrain: Insight the possible mechanisms of action induced by chemotherapeutic agents.

Chemobrain: Insight the possible mechanisms of action induced by chemotherapeutic agents.

DFT, Molecular Docking, Bioactivity and ADME Analyses of Vic-dioxim Ligand Containing Hydrazone Group and its Zn(II) Complex.

Cancer is one of the diseases affecting a large population worldwide and resulting in death. Finding new anti-cancer drugs that are target-focused and have low toxicity is of great importance. This study aimed to investigate the effects of vic-dioxime derivatives carrying hydrazone group and its Zn(II) complex on cancer using molecular docking, bioactivity and quantum chemical calculations. Molecular docking studies were performed on epidermal growth factor receptor and vascular endothelial growth factor receptor 2 target proteins. Furthermore, molecular geometry was performed, and the frontier molecular orbitals, Mulliken charges and molecular electron density distribution were evaluated using density functional theory. Also, the bioactivity parameters of the compounds were evaluated, and ADME analysis was performed using web-based tools. Higher binding affinity was observed for Zn(II) complex with target proteins vascular endothelial growth factor receptor 2 and against epidermal growth factor receptor when compared with LH2. Only the Zn(II) complex against the epidermal growth factor receptor had ligand efficiency and fit quality in the valid range. Furthermore, LH2 has the most potent electrophilic ability (acceptor) among other compounds. Moreover, both LH2 and Zn(II) complexes strongly satisfy Lipinski's rule of five. In conclusion, these novel compounds, especially Zn(II) complex, can be new candidates for anticancer drug development studies which are target-focused and have low toxicity.

A Scoping Review on Recent Progress on Purpurin and its Derivatives

Background: Purpurin is being used as a red dye for many decades. But recently, due to its pharmacological properties, purpurin and its derivatives have attracted a lot of researchers for the treatment of various ailments, such as cancer, Alzheimer’s disease, depression, etc. Objectives: The objective of this study is to provide an overview of its pharmacological properties, pharmacokinetic studies, synthesis, isolation, quality assurance, and patent studies. Method: A systemic scoping review was undertaken. Three databases (Pubmed, Scopus, and Google Scholar) and patent websites were searched using relevant words (e.g., purpurin, purpurin derivatives, anticancer, toxicity, etc.). All outcomes for studies that met the inclusion criteria were included in the review. Extracted data were accumulated using tables, figures, and accompanying narrative descriptive summaries. The review was reported using the preferred reporting items for scoping review (PRISMAScR) guidelines. Sixty-eight studies and eighty-six patents met the inclusion criteria, mostly preclinical (in vitro, in vivo, and in silico) studies performed in rats, mice, dogs, and zebrafish, followed by one clinical trial study. Results: The potent antioxidant nature of purpurin is the main reason behind its vast pharmacological properties. It acts by decreasing mitochondrial stress and by acting on the endoplasmic reticulum. It also crosses the BBB barrier, has high GI absorption, and follows the Lipinski rule, which makes it a good drug for various neurodegenerative disorders. It inhibits various CYP-450, CYP 1A2, and CYP 3A4 enzymes, which are responsible for causing mutations. It gets photosensitized by UV light and causes ROSdependent apoptosis in cancer cells. Conclusion: This scoping review highlights purpurin and its derivatives as highly prized moieties in the treatment of various neurological conditions and cancer. The unique nature of purpurin is responsible for its pharmacological properties, which are due to the presence of hydroxyl and keto groups at specific positions. It gets photosensitized by UV and laser light and acts as an anticancer drug. But the lack of robust evaluation in clinical studies is another major concern. Purpurin can be seen in the prescription in the future, although a lot of work still needs to be done.

Curcumin-Enclosed Nanoparticles for Cancer Therapy

Abstract: Cancer is the greatest cause of mortality worldwide, and it is distinguished by the unrestrained proliferation of a group of aberrant cells, the random division of cells, and the invasiveness of genetically organized cells. At present, there are various strategies for curing of cancer-based on the type &amp; severity. In the earlier two decades, curcumin has received huge attention in pharmacological, biological, and nutraceutical research. In addition to triggering apoptosis in cancer cells, curcumin also inhibits cancer cell invasion and proliferation by stifling cellular signaling pathways. The lower water solubility of curcumin decreases the oral bioavailability, absorption into the systemic circulation, and chemical stability and finally bound the activity of curcumin as an anticancer agent. The pharmacology of curcumin, as well as its derivatives with relation to its anticancer potential, primary modes of action, &amp; cellular target, has been summarised in this article along with a list of the numerous curcumin enclosing nanoformulations. Multiple methods of administration have been developed for curcumin to boost its specificity. Encapsulation and other formulation processing techniques have been found to enhance both the solubility and bioavailability of curcumin. The nanoparticles' size, shape, surface characteristics, and targeting ligand are all factors that nanoformulation designers must think about when working to increase the efficacy and cellular targeting of anticancer treatments.

Advances in non-Hydroxamate based Histone Deacetylase Inhibitors as Anticancer Agents

Advances in non-Hydroxamate based Histone Deacetylase Inhibitors as Anticancer Agents

Immunotherapy in Colorectal Cancer - Finding the Achilles' Heel.

AbstractColorectal cancer treatment has evolved considerably in the last decade with the development of immunotherapies. Immune checkpoint inhibitor therapies have brisk and durable responses in patients with advanced microsatellite instability-high colorectal cancer, both surgically resectable and unresectable; however, patients with microsatellite stable colorectal cancer in general do not respond to the same therapy. Emerging evidence shows that immune checkpoint inhibitors may elicit responses in subsets of patients with microsatellite stable colorectal cancer, especially when combined with other anticancer agents that can modulate the tumor microenvironment. Therefore, rationally designed therapeutic combinations involving immune checkpoint inhibitors, as well as the development of predictive biomarkers for optimal patient selection, have emerged as two key areas of active research. In addition, other immunotherapeutic agents such as cell-based therapies and bispecific T-cell engagers are beginning to be studied in preclinical and early-phase settings. Although by no means a universal treatment strategy, immunotherapy can elicit responses in microsatellite stable colorectal cancer and further research is needed to extend their benefit to patients with microsatellite stable colorectal cancer. Here, we review the current state of immunotherapeutic regimens for microsatellite stable colorectal cancer.

In-vitro Antioxidant, In-vitro and In-silico Ovarian Anticancer Activity (Ovarian Cancer Cells-PA1) and Phytochemical Analysis of Cissus quadrangularis L. Ethanolic Extract.

Cissus quadrangularis is a valuable natural source of traditional medicines. An in vitro investigation was performed to determine whether the ethanolic extract from the whole portions of C. quadrangularis had anticancer and free radical scavenging activities against ovarian cancer cells-PA1. C. quadrangularis is a herb collected from rural areas in Andhra Pradesh, India. C. quadrangularis was air-dried and crushed, and the powder and ethanol (0.5 kg) were used in a Soxhlet device for continuous extraction. Phytochemical analysis of the extracts was performed using a standard procedure. The antioxidant activity of the ethanolic extract of C. quadrangularis was evaluated using DPPH. An in vitro anticancer study used an ethanolic extract against the PA1 cell line. Apoptosis of ovarian cancer cells was studied using DAPI and carboxy-H2DCFDA staining. From LC-MS analysis, quercetin-3-O-alpha-Lrhamnopyranoside and erucic acid were docked with the threonine tyrosine kinase (TTK) enzyme using auto docking. The ethanolic extract of C. quadrangularis demonstrated significant dose-dependent antioxidant activity compared to ascorbic acid. The ethanolic extract of C. quadrangularis was found to have high anticancer activity against ovarian cancer cell lines (PA1), with an IC50 value of 482.057 ± 113.857 μg/ml. DAPI and carboxy-H2DCFDA staining confirmed that C. quadrangularis ethanolic extract induced apoptosis in ovarian cancer cells (p < .001). Molecular docking studies helped identify the binding affinities between the protein and ligand complexes, such as Quercetin-3-O-alpha-Lrhamnopyranoside binding sites of target proteins 5N7V (MET602, GLN672) and erucic acid 5N7V (GLY354). Quercetin-3-O-alpha-L-rhamnopyranoside was reported to bind with 5N7V by hydrogen bonding at MET602 and GLN672 amino acids with 2.02, 2.99 Å bonding length distance and binding affinity of -7.9 kcal/mol. Erucic acid was reported to bind with 5N7V by hydrogen bonding at GLY354 amino acid with 3.18, 2.93 Å bonding length (Å) distance and binding affinity of -4.3 kcal/mol. The current analysis showed that the ethanolic extracts of C. quadrangularis L. exhibited antioxidant and anticancer properties against ovarian PA1 cells. The experimental results confirmed that C. quadrangularis L. is a promising, safe chemotherapeutic plant for ovarian cancer PA1 cells. The docking results demonstrated that Quercetin-3-O-alpha-L-rhamnopyranoside strongly binds threonine tyrosine kinase at the MET602 and GLN672 positions. This study showed that the C. quadrangularis ethanolic extract has Quercetin-3-O-alpha-L-rhamnopyranoside, which can be used as an anticancer agent.

Synthesis of Novel Fluoro Phenyl Triazoles Via Click Chemistry with or without Microwave Irradiation and their Evaluation as Anti-proliferative Agents in SiHa Cells.

Perform the synthesis of novel fluoro phenyl triazoles via click chemistry with or without microwave irradiation and their evaluation as anti-proliferative agents in SiHa cells. Triazoles are heterocyclic compounds containing a five-member ring with two carbon and three nitrogen atoms. They are of great importance since many of them have shown to have biological activity as antifungal, antiviral, antibacterial, anti-HIV, anti-tuberculosis, vasodilator, and anticancer agents. Synthesize novel fluoro phenyl triazoles via click chemistry and evaluate their antiproliferative activity. First, several fluorophenyl azides were prepared. Reacting these aryl azides with phenylacetylene in the presence of Cu(I) catalyst, the corresponding fluoro phenyl triazoles were obtained by two methodologies, stirring at room temperature and under microwave irradiation at 40ºC. In addition, their antiproliferative activity was evaluated in cervical cancer SiHa cells. Fluoro phenyl triazoles were obtained within minutes by means of microwave irradiation. The compound 3f, containing two fluorine atoms next to the carbon connected to the triazole ring, was the most potent among the fluoro phenyl triazoles tested in this study. Interestingly, the addition of a fluorine atom to the phenyl triazole structure in a specific site increases its antiproliferative effect as compared to parent phenyl triazole 3a without a fluorine atom. Several fluoro phenyl triazoles were obtained by reacting fluoro phenyl azides with phenylacetylene in the presence of copper sulphate, sodium ascorbate and phenanthroline. Preparation of these triazoles with MW irradiation represents a better methodology since they are obtained within minutes and higher yields of cleaner compounds are obtained. In terms of biological studies, the proximity between fluorine atom and triazole ring increases its biological activity.

Synergistic Effects of Neratinib in Combination With Palbociclib or Miransertib in Brain Cancer Cells.

Aberrant expression and activation of epidermal growth factor receptor (EGFR) resulted in approval of several forms of EGFR inhibitors in the treatment of patients with a wide range of epithelial cancers. However, no EGFR inhibitor has yet been approved for the treatment of patients with brain cancer, indicating that targeting EGFR alone may not be sufficient in some patients. In this study, we investigated the role of all members of the EGFR family, other growth factor receptors, cell-cycle proteins, and downstream cell signaling pathways (e.g., mitogen-activated protein kinase (MAPK), serine/threonine protein kinase (AKT), signal transducer and activator of transcription (STAT3), Src, Abelson murine leukemia viral oncogene homolog (Abl)) on the growth of a panel of human brain cancer cell lines (HBCCLs). We examined the growth response of HBCCLs to treatment with 17 targeted agents compared to two cytotoxic drugs. Of the targeted agents, the irreversible pan-human epidermal growth factor receptor (HER) inhibitors neratinib and afatinib were more effective than erlotinib and lapatinib at inhibiting the growth of all HBCCLs, and the cyclin-dependent kinase (CDK)1/2/5/9 inhibitor dinaciclib was the most potent targeted agent. We found that treatment with Src/Abl/c-kit inhibitor dasatinib, signal transducer and activator of transcription (STAT3) inhibitor stattic, Abl/platelet-derived growth factor receptor (PDGFR)α/vascular endothelial growth factor (VEGFR)2/fibroblast growth factor receptor (FGFR)1 inhibitor ponatinib, and the tropomyosin receptor kinase (TRK)/ROS proto-oncogene 1 receptor tyrosine kinase (ROS)/anaplastic lymphoma kinase (ALK) inhibitor entrectinib, also inhibited the growth of all HBCCLs. Interestingly, these agents were more effective in inhibiting growth of HBCCLs when proliferating at a slower rate. In addition to inhibiting the proliferation of HBCCLs, treatment with neratinib, dinaciclib, dasatinib, stattic and trametinib inhibited the migration of brain tumor cell line A172. Notably, we found that treatment with neratinib in combination with palbociclib (CDK4/6 inhibitor), or miransertib (AKT1/2/3 inhibitor) resulted in synergistic growth inhibition of all HBCCLs. Our results support that repurposing drugs like neratinib in combination with the palbociclib or miransertib may be of therapeutic potential in brain cancer and warrants further investigations.

Identification of Cancer Stem Cell-related Gene by Single-cell and Machine Learning Predicts Immune Status, Chemotherapy Drug, and Prognosis in Lung Adenocarcinoma.

This study aimed to identify the molecular type and prognostic model of lung adenocarcinoma (LUAD) based on cancer stem cell-related genes. Studies have shown that cancer stem cells (CSC) are involved in the development, recurrence, metastasis, and drug resistance of tumors. The clinical information and RNA-seq of LUAD were obtained from the TCGA database. scRNA dataset GSE131907 and 5 GSE datasets were downloaded from the GEO database. Molecular subtypes were identified by ConsensusClusterPlus. A CSC-related prognostic signature was then constructed via univariate Cox and LASSO Cox-regression analysis. A scRNA-seq GSE131907 dataset was employed to obtain 11 cell clusters, among which, 173 differentially expressed genes in CSC were identified. Moreover, the CSC score and mRNAsi were higher in tumor samples. 18 of 173 genes were survival time-associated genes in both the TCGA-LUDA dataset and the GSE dataset. Next, two molecular subtypes (namely, CSC1 and CSC2) were identified based on 18 survival-related CSC genes with distinct immune profiles and noticeably different prognoses as well as differences in the sensitivity of chemotherapy drugs. 8 genes were used to build a prognostic model in the TCGA-LUAD dataset. High-risk patients faced worse survival than those with a low risk. The robust predictive ability of the risk score was validated by the time-dependent ROC curve revealed as well as the GSE dataset. TIDE analysis showed a higher sensitivity of patients in the low group to immunotherapy. This study has revealed the effect of CSC on the heterogeneity of LUAD, and created an 8 genes prognosis model that can be potentially valuable for predicting the prognosis of LUAD and response to immunotherapy.

A mathematical model to study low-dose metronomic scheduling for chemotherapy

Metronomic chemotherapy refers to the frequent administration of chemotherapeutic agents at a lower dose and presents an attractive alternative to conventional chemotherapy with encouraging response rates. However, the schedule of the therapy, including the dosage of the drug, is usually based on empiricism. The confounding effects of tumor-endothelial-immune interactions during metronomic administration of drugs have not yet been explored in detail, resulting in an incomplete assessment of drug dose and frequency evaluations. The present study aimed to gain a mechanistic understanding of different actions of metronomic chemotherapy using a mathematical model. We have established an analytical condition for determining the dosage and frequency of the drug depending on its clearance rate for complete tumor elimination. The model also brings forward the immune-mediated clearance of the tumor during the metronomic administration of the chemotherapeutic agent. The results from the global sensitivity analysis showed an increase in the sensitivity of drug and immune-mediated killing factors toward the tumor population during metronomic scheduling. Our results emphasize metronomic scheduling over the maximum tolerated dose (MTD) and define a model-based approach for approximating the optimal schedule of drug administration to eliminate tumors while minimizing harm to the immune cells and the patient’s body.

Pleurotus pulmonarius polysaccharides inhibit glioma growth through the Hippo signaling pathway and regulate the structure of gut microbiota

Pleurotus pulmonarius (Fr.) is an edible and medicinal fungus. Here, we isolated polysaccharides from P. pulmonarius and evaluated their physicochemical properties, anti-tumor activity, and gut microbiota regulation. Freeze-dried powder of P. pulmonarius fruiting body polysaccharide (PFP) is a heteropolysaccharide, mainly composed of galactose (295.52 μg/mg). PFP significantly inhibited glioma cell survival in vitro and U251 glioma cell tumor growth in nude mice (inhibition rate, 53.70%). PFP inhibited YAP1 and TAZ protein expression levels, upregulated those of MST1 and LAST1, regulated Hippo signaling, stimulated E-cadherin, and downregulated N-cadherin proteins, inhibiting tumor migration. PFP downregulated Bcl-2 protein expression, upregulated that of Cleaved Caspase 3, and induced tumor cell apoptosis. PFP regulated gut microbiota structure in tumor-bearing nude mice and increased the relative abundance of beneficial bacteria. In summary, PFP is a natural, safe, and non-toxic anti-cancer drug, and a potential probiotic. Our data provide theoretical guidance for the treatment of glioma.

Green Approach Toward Triazole Forming Reactions for Developing Anticancer Drugs.

Compounds containing triazole have many significant applications in the dye and ink industry, corrosion inhibitors, polymers, and pharmaceutical industries. These compounds possess many antimicrobial, antioxidant, anticancer, antiviral, anti-HIV, antitubercular, and anticancer activities. Several synthetic methods have been reported for reducing time, minimizing synthetic steps, and utilizing less hazardous and toxic solvents and reagents to improve the yield of triazoles and their analogues synthesis. Among the improvement in methods, green approaches towards triazole forming biologically active compounds, especially anticancer compounds, would be very important for pharmaceutical industries as well as global research community. In this article, we have reviewed the last five years of green chemistry approaches on click reaction between alkyl azide and alkynes to install 1,2,3-triazole moiety in natural products and synthetic drug-like molecules, such as in colchicine, flavanone cardanol, bisphosphonates, thiabendazoles, piperazine, prostanoid, flavonoid, quinoxalines, C-azanucleoside, dibenzylamine, and aryl-azotriazole. The cytotoxicity of triazole hybrid analogues was evaluated against a panel of cancer cell lines, including multidrug-resistant cell lines.

Two-dimensional MXene-based nano-prodrug for synergistic chemo-photothermal therapy on cancer treatment

In cancer treatment, although prodrugs have been developed to overcome obstacles such as undesirable pharmacokinetic performance and serious off-target toxicity of most chemotherapeutics, the combination of prodrugs with nanotechnology could be used to overcome the shortcomings of conventional prodrug strategies and facilitate more efficient drug delivery and accumulation of anticancer prodrugs at specific sites/tissues. Phototherapy is a method that uses near-infrared (NIR) light to achieve local and non-invasive tumor therapy. The combination of chemotherapy and phototherapy has shown many therapeutic advantages, including synergistic therapeutic effects and the reduction of toxic and side effects of drugs through dose reduction. In this work, a hydrazone linkage was reported to conjugate Ti3C2Tx MXene nanosheets with doxorubicin hydrochloride (DOX) and methoxy poly(ethylene glycol) benzaldehyde (mPEG-CHO) through a chemical surface modification to form a two-dimensional (2D) nano-prodrug Ti3C2Tx-DOX/PEG (TDP) for synergistic chemo-photothermal therapy. First, hydrazide functionalized Ti3C2Tx was obtained. Then, the carbonyl group of DOX and the aldehyde group of mPEG-CHO can form a pH-responsive hydrazone bond with hydrazide-functionalized Ti3C2Tx. The high surface area of Ti3C2Tx could overcome the reduced drug loading caused by conjugation. Aqueous stability and biocompatibility were enhanced by the introduction of PEG, making the material capable of prolonged circulation in the body’s bloodstream. By achieving excellent antitumor results with this nano-prodrug, we have added another brick to the edifice of Ti3C2Tx MXene as an anticancer drug carrier, and given new vitality to the study of anticancer prodrugs combined with nanotechnology.

Evaluation of Doxorubicin-loaded Echogenic Macroemulsion for Targeted Drug Delivery.

The latest technology trend in targeted drug delivery highlights stimuliresponsive particles that can release an anticancer drug in a solid tumor by responding to external stimuli. This study aims to design, fabricate, and evaluate an ultrasound-responsive drug delivery vehicle for an ultrasound-mediated drug delivery system. The drug-containing echogenic macroemulsion (eME) was fabricated by an emulsification method using the three phases (aqueous lipid solution as a shell, doxorubicin (DOX) contained oil, and perfluorohexane (PFH) as an ultrasound-responsive agent). The morphological structure of eMEs was investigated using fluorescence microscopy, and the size distribution was analyzed by using DLS. The echogenicity of eME was measured using a contrast-enhanced ultrasound device. The cytotoxicity was evaluated using a breast cancer cell (MDA-MB-231) via an in vitro cell experiment. The obtained eME showed an ideal morphological structure that contained both DOX and PFH in a single particle and indicated a suitable size for enhancing ultrasound response and avoiding complications in the blood vessel. The echogenicity of eME was demonstrated via an in vitro experiment, with results showcasing the potential for targeted drug delivery. Compared to free DOX, enhanced cytotoxicity and improved drug delivery efficiency in a cancer cell were proven by using DOX-loaded eMEs and ultrasound. This study established a platform technology to fabricate the ultrasound-responsive vehicle. The designed drug-loaded eME could be a promising platform with ultrasound technology for targeted drug delivery.