Silvestrol, a potent anticancer agent with unfavourable pharmacokinetics: Current knowledge on its pharmacological properties and future directions for the development of novel drugs.

Cancer remains a leading cause of death, with increasing incidence. Conventional treatments offer limited efficacy and cause significant side effects, hence novel drugs with improved pharmacological properties and safety are required. Silvestrol (SLV) is a flavagline derived from some plants of the Aglaia genus that has shown potent anticancer effects, warranting further study. Despite its efficacy in inhibiting the growth of several types of cancer cells, SLV is characterized by an unfavorable pharmacokinetics that hamper its use as a drug. A consistent research over the recent years has led to develop novel SLV derivatives with comparable pharmacodynamics and an ameliorated pharmacokinetic profile, demonstrating potential applications in the clinical management of cancer. This comprehensive review aims to highlight the most recent data available on SLV and its synthetic derivatives, addressing their pharmacological profile and therapeutic potential in cancer treatment. A systematic literature review of both in vitro and in vivo studies focusing on anticancer effects, pharmacodynamics, and pharmacokinetics of these compounds is presented. Overall, literature data highlight that rationale chemical modifications of SLV are critical for the development of novel drugs with high efficacy on a broad variety of cancers and improved bioavailability in vivo. Nevertheless, SLV analogues need to be further studied to better understand their mechanisms of action, which can be partially different to SLV. Furthermore, clinical research is still required to assess their efficacy in humans and their safety.

Unlocking the Power of Human Ferritin: Enhanced Drug Delivery of Aurothiomalate in A2780 Ovarian Cancer Cells.

Aurothiomalate (AuTM) is an FDA-approved antiarthritic gold drug with unique anticancer properties. To enhance its anticancer activity, we prepared a bioconjugate with human apoferritin (HuHf) by attaching some AuTM moieties to surface protein residues. The reaction of apoferritin with excess AuTM yielded a single adduct, that was characterized by ESI MS and ICP-OES analysis, using three mutant ferritins and trypsinization experiments. The adduct contains ~3 gold atoms per ferritin subunit, arranged in a small cluster bound to Cys90 and Cys102. MD simulations provide a plausible structural model for the cluster. The adduct was evaluated for its pharmacological properties and was found to be significantly more cytotoxic than free AuTM against A2780 cancer cells mainly due to higher gold uptake. NMR-metabolomics showed that AuTM bound to HuHf and free AuTM induced qualitatively similar changes in treated cancer cells, indicating that the effects on cell metabolism are approximately the same, in agreement with independent biochemical experiments. In conclusion, we have demonstrated here that a molecularly precise bioconjugate formed between AuTM and HuHf exhibits anticancer properties far superior to the free drug, while retaining its key mechanistic features. Evidence is provided that human ferritin can serve as an excellent carrier for this metallodrug.

Successful treatment and remission of advanced testicular cancer after COVID-19 infection during induction chemotherapy.

Introduction: We report a case of advanced testicular cancer cured by early and appropriate resumption of chemotherapy even after COVID-19 infection during induction chemotherapy. Case presentation: The patient was a healthy 36-year-old male. The diagnosis was a stage IIIB nonseminoma (pT2N2M1a). On day 14 of the first chemotherapy cycle, the patient was diagnosed with mild COVID-19. The second chemotherapy cycle was initiated with a 1-day delay (on day 10 after the COVID-19 diagnosis). The patient achieved remission with minimal postponement of chemotherapy. Conclusion: Only a few case reports have described the resumption of anticancer chemotherapy in patients with COVID-19. In deciding when to resume chemotherapy after COVID-19 infection, it is essential to consider factors such as cancer type, progression, and severity of COVID-19 and should be tailored to individual patient needs.

Pistacia and its Combination with Cisplatin: A Potential Anticancer Candidate by Modulating Apoptotic Genes.

INTRODUCTION: Many bioactive phytochemicals have essential significance for handling various diseases and developing new drugs. The aim was to investigate the anti-tumor activity and the underlying mechanisms of pistachio pericarp extract (PPE) and pistachio kernel extract (PKE) alone and combined with cisplatin (CP) in the treatment of prostate cancer. METHODS: The effects of the PPE, PKE, and CP alone and PPE and PKE in combination with CP (PPE+CP and PKE+CP) on the proliferation of PC-3 cells were determined using the MTT assay. The fold changes of BAX, BCL-2, P53, KLK2, TNF, TGF, and NANOG expression against ß-actin were determined by real-time technique. Data were analyzed by two-way ANOVA and repeated measure tests. RESULTS: These research results indicated that a greater anti-proliferative effect of the PPE and PKE was shown in combination with CP compared with treatments using the PPE and PKE or CP alone. The extracts and Cisplatin in vitro had good synergistic effects on the inhibition of the proliferation of PC-3 cells. The IC50 values of PKE+CP were 4.141, 2.140, and 0.884 ug/mL, and PPE+CP were 2.754, 2.061, and 0.753 ug/mL after 24h, 48 h, and 72h treatment, respectively. Also, this result presented that the mRNA expression of BAX and P53 increased, and BCL-2, KLK2, TNF, TGF, and NANOG decreased in PC-3 cells. CONCLUSIONS: The finding of this research showed for the first time the anti-carcinogenesis effects of separately and in the combination of PPE, PKE, and CP on the PC-3 prostate cancer cells via modulating some genes and that it may be nominated for the herbal anti-cancer medications.

Molecular Targets of Plant-based Alkaloids and Polyphenolics in Liver and Breast Cancer- An Insight into Anticancer Drug Development.

Liver and Breast cancer are ranked as the most prevailing cancers that cause high cancer-related mortality. As cancer is a life-threatening disease that affects the human population globally, there is a need to develop novel therapies. Among the available treatment options include radiotherapy, chemotherapy, surgery, and immunotherapy. The most superlative modern method is the use of plant-derived anticancer drugs that target the cancerous cells and inhibit their proliferation. Plant-derived compounds are generally considered safer than synthetic drugs/traditional therapies and could serve as potential novel targets to treat liver and breast cancer to revolutionize cancer treatment. Alkaloids and Polyphenols have been shown to act as anticancer agents through molecular approaches. They disrupt various cellular mechanisms, inhibit the production of cyclins and CDKs to arrest the cell cycle, and activate the DNA repairing mechanism by upregulating p53, p21, and p38 expression. In severe cases, when no repair is possible, they induce apoptosis in liver and breast cancer cells by activating caspase-3, 8, and 9 and increasing the Bax/Bcl-2 ratio. They also deactivate several signaling pathways, such as PI3K/AKT/mTOR, STAT3, NF-kB, Shh, MAPK/ERK, and Wnt/ß-catenin pathways, to control cancer cell progression and metastasis. The highlights of this review are the regulation of specific protein expressions that are crucial in cancer, such as in HER2 over-expressing breast cancer cells; alkaloids and polyphenols have been reported to reduce HER2 as well as MMP expression. This study reviewed more than 40 of the plant-based alkaloids and polyphenols with specific molecular targets against liver and breast cancer. Among them, Oxymatrine, Hirsutine, Piperine, Solamargine, and Brucine are currently under clinical trials by qualifying as potent anticancer agents due to lesser side effects. As a lot of research is there on anticancer compounds, there is a desideratum to compile data to move towards clinical trials phase 4 and control the prevalence of liver and breast cancer.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Preparation of poly(vinyl alcohol) nanofibers containing disulfiram-copper complex by electrospinning: a potential delivery system against melanoma.

BACKGROUND: Melanoma poses a significant threat to human health, making the development of a safe and effective treatment a crucial challenge. Disulfiram (DS) is a proven anticancer drug that has shown effectiveness when used in combination with copper (DS-Cu complex). OBJECTIVES: This study focuses on encapsulation of DS-copper complex into nanofiber scaffold from polyvinyl alcohol (PVA) (DS-Cu@PVA). In order to increase bioavailability towards melanoma cell lines and decrease its toxicity. METHODS: The scaffold was fabricated through an electrospinning process using an aqueous solution, and subsequently analyzed using ART-Fourier transform infrared spectroscopy (ART-FTIR), scanning electron microscopy (SEM), and energy dispersive X-ray analysis (EDX). Additionally, cellular cytotoxicity, flow cytometry analysis, and determination of caspase 3 activity were conducted to further characterize the scaffold. RESULTS: The results confirmed that encapsulation of DS-Cu complex into PVA was successful via different characterization. The scanning electron microscopy (SEM) analysis revealed that the diameter of the nanofibers remained consistent despite the addition of DS-Cu. Additionally, ATR-FTIR confirmed that the incorporation of DS-Cu into PVA did not significantly alter the characteristic peaks of PVA. Furthermore, the cytotoxicity assessment of the DS-Cu@PVA nanofibrous scaffold using human normal skin cells (HFB4) demonstrated its superior biocompatibility compared to DS-Cu-free counterparts. Notably, the presence of DS-Cu maintained its effectiveness in promoting apoptosis by increasing cellular reactive oxygen species, proapoptotic gene expression, and caspase 3 activity, while simultaneously reducing glutathione levels and oncogene expression in human and mouse melanoma cell lines (A375 and B16F10, respectively). Overall, these findings suggest that the addition of DS-Cu to PVA nanofibers enhances their biocompatibility and cytotoxic effects on melanoma cells, making them a promising candidate for biomedical applications. CONCLUSION: The findings indicate that the targeted delivery of DS-Cu onto a PVA nanofiber scaffold holds potential approach to enhance the efficacy of DS-Cu in combating melanoma.

Green, facile synthesis and evaluation of unsymmetrical carbamide derivatives as antimicrobial and anticancer agents with mechanistic insights.

A very practical method for the synthesis of unsymmetrical carbamide derivatives in good to excellent yield was presented, without the need for any catalyst and at room temperature. Using a facile and robust protocol, fifteen unsymmetrical carbamide derivatives (9-23) bearing different aliphatic amine moieties were designed and synthesized by the reaction of secondary aliphatic amines with isocyanate derivatives in the presence of acetonitrile as an appropriate solvent in good to excellent yields. Trusted instruments like IR, mass spectrometry, NMR spectra, and elemental analyses were employed to validate the purity and chemical structures of the synthesized compounds. All the synthesized compounds were tested as antimicrobial agents against some clinically bacterial pathogens such as Salmonella typhimurium, Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. Compounds 15, 16, 17, 19 and 22 showed potent antimicrobial activity with promising MIC values compared to the positive controls. Moreover, compounds 15 and 22 provide a potent lipid peroxidation (LPO) of the bacterial cell wall. On the other hand, we investigated the anti-proliferative activity of compounds 9-23 against selected human cancerous cell lines of breast (MCF-7), colon (HCT-116), and lung (A549) relative to healthy noncancerous control skin fibroblast cells (BJ-1). The mechanism of their cytotoxic activity has been also examined by immunoassaying the levels of key anti- and pro-apoptotic protein markers. The results of MTT assay revealed that compounds 10, 13, 21, 22 and 23 possessed highly cytotoxic effects. Out of these, three synthesized compounds 13, 21 and 22 showed cytotoxicity with IC50 values (13, IC50 = 62.4 ± 0.128 and 22, IC50 = 91.6 ± 0.112 µM, respectively, on MCF-7), (13, IC50 = 43.5 ± 0.15 and 21, IC50 = 38.5 ± 0.17 µM, respectively, on HCT-116). Cell cycle and apoptosis/necrosis assays demonstrated that compounds 13 and 22 induced S and G2/M phase cell cycle arrest in MCF-7 cells, while only compound 13 had this effect on HCT-116 cells. Furthermore, compound 13 exhibited the greatest potency in inducing apoptosis in both cell lines compared to compounds 21 and 22. Docking studies indicated that compounds 10, 13, 21 and 23 could potentially inhibit enzymes and exert promising antimicrobial effects, as evidenced by their lower binding energies and various types of interactions observed at the active sites of key enzymes such as Sterol 14-demethylase of C. albicans, Dihydropteroate synthase of S. aureus, LasR of P. aeruginosa, Glucosamine-6-phosphate synthase of K. pneumenia and Gyrase B of B. subtilis. Moreover, 13, 21, and 22 demonstrated minimal binding energy and favorable affinity towards the active pocket of anticancer receptor proteins, including CDK2, EGFR, Erα, Topoisomerase II and VEGFFR. Physicochemical properties, drug-likeness, and ADME (absorption, distribution, metabolism, excretion, and toxicity) parameters of the selected compounds were also computed.

Exploring chromone-2-carboxamide derivatives for triple-negative breast cancer targeting EGFR, FGFR3, and VEGF pathways: Design, synthesis, and preclinical insights.

Chromone-based compounds have established cytotoxic, antiproliferative, antimetastatic, and antiangiogenic effects on various cancer cell types via modulating different molecular targets. Herein, 17 novel chromone-2-carboxamide derivatives were synthesized and evaluated for their in vitro anticancer activity against 15 human cancer cell lines. Among the tested cell lines, MDA-MB-231, the triple-negative breast cancer cell line, was found to be the most sensitive, where the N-(2-furylmethylene) (15) and the α-methylated N-benzyl (17) derivatives demonstrated the highest growth inhibition with GI50 values of 14.8 and 17.1 µM, respectively. In vitro mechanistic studies confirmed the significant roles of compounds 15 and 17 in the induction of apoptosis and suppression of EGFR, FGFR3, and VEGF protein levels in MDA-MB-231 cancer cells. Moreover, compound 15 exerted cell cycle arrest at both the G0-G1 and G2-M phases. The in vivo efficacy of compound 15 as an antitumor agent was further investigated in female mice bearing Solid Ehrlich Carcinoma. Notably, administration of compound 15 resulted in a marked decrease in both tumor weight and volume, accompanied by improvements in biochemical, hematological, histological, and immunohistochemical parameters that verified the repression of both angiogenesis and inflammation as additional Anticancer mechanisms. Moreover, the binding interactions of compounds 15 and 17 within the binding sites of all three target receptors (EGFR, FGFR3, and VEGF) were clearly illustrated using molecular docking.

Cardiovascular disease burden in patients with urological cancers: The new discipline of uro-cardio-oncology.

Cancer remains a major cause of mortality worldwide, and urological cancers are the most common cancers among men. Several therapeutic agents have been used to treat urological cancer, leading to improved survival for patients. However, this has been accompanied by an increase in the frequency of survivors with cardiovascular complications caused by anticancer medications. Here, we propose the novel discipline of uro-cardio-oncology, an evolving subspecialty focused on the complex interactions between cardiovascular disease and urological cancer. In this comprehensive review, we discuss the various cardiovascular toxicities induced by different classes of antineoplastic agents used to treat urological cancers, including androgen deprivation therapy, vascular endothelial growth factor receptor tyrosine kinase inhibitors, immune checkpoint inhibitors, and chemotherapeutics. In addition, we discuss possible mechanisms underlying the cardiovascular toxicity associated with anticancer therapy and outline strategies for the surveillance, diagnosis, and effective management of cardiovascular complications. Finally, we provide an analysis of future perspectives in this emerging specialty, identifying areas in need of further research.

Microbiome-driven anticancer therapy: A step forward from natural products.

Human microbiomes, considered as a new emerging and enabling cancer hallmark, are increasingly recognized as critical effectors in cancer development and progression. Manipulation of microbiome revitalizing anticancer therapy from natural products shows promise toward improving cancer outcomes. Herein, we summarize our current understanding of the human microbiome-driven molecular mechanisms impacting cancer progression and anticancer therapy. We highlight the potential translational and clinical implications of natural products for cancer prevention and treatment by developing targeted therapeutic strategies as adjuvants for chemotherapy and immunotherapy against tumorigenesis. The challenges and opportunities for future investigations using modulation of the microbiome for cancer treatment are further discussed in this review.

Biosynthesis of zinc oxide nanoparticles via neem extract and their anticancer and antibacterial activities.

In the present study, zinc oxide nanoparticles (ZnO-NPs) were synthesized using neem leaf aqueous extracts and characterized using transmission electron microscopy (TEM), ultraviolet visible spectroscopy (UV-Vis), and dynamic light scattering (DLS). Then compare its efficacy as anticancer and antibacterial agents with chemically synthesized ZnO-NPs and the neem leaf extract used for the green synthesis of ZnO-NPs. The TEM, UV-vis, and particle size confirmed that the developed ZnO-NPs are nanoscale. The chemically and greenly synthesized ZnO-NPs showed their optical absorbance at 328 nm and 380 nm, respectively, and were observed as spherical particles with a size of about 85 nm and 62.5 nm, respectively. HPLC and GC-MS were utilized to identify the bioactive components in the neem leaf aqueous extract employed for the eco-friendly production of ZnO-NPs. The HPLC analysis revealed that the aqueous extract of neem leaf contains 19 phenolic component fractions. The GC-MS analysis revealed the existence of 21 bioactive compounds. The antiproliferative effect of green ZnO-NPs was observed at different concentrations (31.25 µg/mL-1000 µg/mL) on Hct 116 and A 549 cancer cells, with an IC50 value of 111 µg/mL for A 549 and 118 µg/mL for Hct 116. On the other hand, the antibacterial activity against gram-positive and gram-negative bacteria was estimated. The antibacterial result showed that the MIC of green synthesized ZnO-NPs against gram-positive and gram-negative bacteria were 5, and 1 µg/mL. Hence, they could be utilized as effective antibacterial and antiproliferative agents.

Antioxidant and antiproliferative activity of enzymatic hydrolysates from red tilapia (Oreochromis spp.) viscera.

The antioxidant and antiproliferative activity of red tilapia (Oreochromis spp.) viscera hydrolysates (RTVH) was evaluated. For that, the hydrolysates was applied to three cancer cell lines (HepG2, Huh7 and SW480) and the control (CCD-18Co). Finally, the line on which the hydrolysate had the greatest effect (SW480) and the control (CCD-18Co) were subjected to the ApoTox-Glo Triplex Assay to determine apoptosis, toxicity, and cell viability. The result showed that hydrolysate had a dose-dependent cytotoxic effect selective on the three cancer cell lines, compared to the control cells. There is a relationship between the antioxidant capacity of RTVHs and their antiproliferative capacity on cancer cells evaluated, which achieved cell viability by action of RTVH of 34.68 and 41.58 and 25.41 %, to HepG2, Huh7 and SW480, respectively. The action of RTVH on cancer cell line SW480 is not due to the induction of apoptosis but to the rupture of the cell membrane.

Investigating the potential of monocyclic B9N9 and C18 rings for the electrochemical sensing, and adsorption of carbazole-based anti-cancer drug derivatives: DFT-based first-principle study.

CONTEXT: For the first time, the use of monocyclic rings C18 and B9N9 as sensors for the sensing of carbazole-based anti-cancer drugs, such as tetrahydrocarbazole (THC), mukonal (MKN), murrayanine (MRY), and ellipticine (EPT), is described using DFT simulations and computational characterization. The geometries, electronic properties, stability studies, sensitivity, and adsorption capabilities of C18 and B9N9 counterparts towards the selected compounds confirm that the analytes interact through active cavities of the C18 and B9N9 rings of the complexes. METHODS: Based on the interaction energies, the sensitivity of surfaces towards EPT, MKN, MRY, and THC analytes is observed. The interaction energy of EPT@B9N9, MKN@B9N9, MRY@B9N9, and THC@B9N9 complexes are observed - 20.40, - 19.49, - 20.07, and - 18.27 kcal/mol respectively which is more exothermic than EPT@C18, MKN@C18, MRY@C18, and THC@C18 complexes are - 16.37, - 13.97, - 13.96, and - 11.39 kcal/mol respectively. According to findings from the quantum theory of atoms in molecules (QTAIM) and the reduced density gradient (RDG), dispersion forces play a significant role in maintaining the stability of these complexes. The electronic properties including FMOs, density of states (DOS), natural bond orbitals (NBO), charge transfer, and absorption studies are carried out. In comparison of B9N9 and C18, the analyte recovery time for C18 is much shorter (9.91 × 10-11 for THC@C18) than that for B9N9 shorter recovery time value of 3.75 × 10-9 for EPT@B9N9. These results suggest that our reported sensors B9N9 and C18 make it faster to detect adsorbed molecules at room temperature. The sensor response is more prominent in B9N9 due to its fine energy gap and high adsorption energy. Consequently, it is possible to think of these monocyclic systems as a potential material for sensor applications.

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.

A Lipid-Sensitive Spider Peptide Toxin Exhibits Selective Anti-Leukemia Efficacy through Multimodal Mechanisms.

Anti-cancer peptides (ACPs) represent a promising potential for cancer treatment, although their mechanisms need to be further elucidated to improve their application in cancer therapy. Lycosin-I, a linear amphipathic peptide isolated from the venom of Lycosa singorensis, shows significant anticancer potential. Herein, it is found that Lycosin-I, which can self-assemble into a nanosphere structure, has a multimodal mechanism of action involving lipid binding for the selective and effective treatment of leukemia. Mechanistically, Lycosin-I selectively binds to the K562 cell membrane, likely due to its preferential interaction with negatively charged phosphatidylserine, and rapidly triggers membrane lysis, particularly at high concentrations. In addition, Lycosin-I induces apoptosis, cell cycle arrest in the G1 phase and ferroptosis in K562 cells by suppressing the PI3K-AKT-mTOR signaling pathway and activating cell autophagy at low concentrations. Furthermore, intraperitoneal injection of Lycosin-I inhibits tumor growth of K562 cells in a nude mouse xenograft model without causing side effects. Collectively, the multimodal effect of Lycosin-I can provide new insights into the mechanism of ACPs, and Lycosin-I, which is characterized by high potency and specificity, can be a promising lead for the development of anti-leukemia drugs.

Antibody-drug conjugates combinations in cancer treatment.

Antibody-drug conjugates (ADCs) have emerged as a promising class of anticancer agents. Currently, the Food and Drug Administration has granted approval to 12 compounds, with 2 later undergoing withdrawal. Moreover, several other compounds are currently under clinical development at different stages. Despite substantial antitumoral activity observed among different tumor types, adverse events and the development of resistance represent significant challenges in their use. Over the last years, an increasing number of clinical trials have been testing these drugs in different combinations with other anticancer agents, such as traditional chemotherapy, immune checkpoint inhibitors, monoclonal antibodies, and small targeted agents, reporting promising results based on possible synergistic effects and a potential for improved treatment outcomes among different tumor types. Here we will review combinations of ADCs with other antitumor agents aiming at describing the current state of the art and future directions.

Advancements and recent explorations of anti-cancer activity of chrysin: from molecular targets to therapeutic perspective.

In recent times, there have been notable advancements in comprehending the potential anti-cancer effects of chrysin (CH), a naturally occurring flavonoid compound found abundantly in various plant sources like honey, propolis, and certain fruits and vegetables. This active compound has garnered significant attention due to its promising therapeutic qualities and minimal toxicity. CH's ability to combat cancer arises from its multifaceted mechanisms of action, including the initiation of apoptosis and the inhibition of proliferation, angiogenesis, metastasis, and cell cycle progression. CH also displays potent antioxidant and anti-inflammatory properties, effectively counteracting the harmful molecules that contribute to DNA damage and the development of cancer. Furthermore, CH has exhibited the potential to sensitize cancer cells to traditional chemotherapy and radiotherapy, amplifying the effectiveness of these treatments while reducing their negative impact on healthy cells. Hence, in this current review, the composition, chemistry, mechanisms of action, safety concerns of CH, along with the feasibility of its nanoformulations. To conclude, the recent investigations into CH's anti-cancer effects present a compelling glimpse into the potential of this natural compound as a complementary therapeutic element in the array of anti-cancer approaches, providing a safer and more comprehensive method of combating this devastating ailment.

Diospyros rhodocalyx Kurz induces mitochondrial-mediated apoptosis via BAX, Bcl-2, and caspase-3 pathways in LNCaP human prostate cancer cell line.

Background: Prostate cancer (PCa) is one of the causes of death in men worldwide. Although treatment strategies have been developed, the recurrence of the disease and consequential side effects remain an essential concern. Diospyros rhodocalyx Kurz, a traditional Thai medicine, exhibits diverse therapeutic properties, including anti-cancer activity. However, its anti-cancer activity against prostate cancer has not been thoroughly explored. This study aims to evaluate the anti-cancer activity and underlying mechanisms of the ethyl acetate extract of D. rhodocalyx Kurz (EADR) related to apoptosis induction in the LNCaP human prostate cancer cell line. Methods: Ethyl acetate was employed to extract the dried bark of D. rhodocalyx Kurz. The cytotoxicity of EADR on both LNCaP and WPMY-1 cells (normal human prostatic myofibroblast cell line) was evaluated using MTS assay. The effect of EADR on the cell cycle, apoptosis induction, and alteration in mitochondrial membrane potential (MMP) was assessed by the staining with propidium iodide (PI), Annexin V-FITC/PI, and JC-1 dye, respectively. Subsequent analysis was conducted using flow cytometry. The expression of cleaved caspase-3, BAX, and Bcl-2 was examined by Western blotting. The phytochemical profiling of the EADR was performed using gas chromatography-mass spectrometry (GC-MS). Results: EADR exhibited a dose-dependent manner cytotoxic effect on LNCaP cells, with IC50 values of 15.43 and 12.35 µg/mL after 24 and 48 h, respectively. Although it also exhibited a cytotoxic effect on WPMY-1 cells, the effect was comparatively lower, with the IC50 values of 34.61 and 19.93 µg/mL after 24 and 48 h of exposure, respectively. Cell cycle analysis demonstrated that EADR did not induce cell cycle arrest in either LNCaP or WPMY-1 cells. However, it significantly increased the sub-G1 population in LNCaP cells, indicating a potential induction of apoptosis. The Annexin V-FITC/PI staining indicated that EADR significantly induced apoptosis in LNCaP cells. Subsequent investigation into the underlying mechanism of EADR-induced apoptosis revealed a reduction in MMP as evidenced by JC-1 staining. Moreover, Western blotting demonstrated that EADR treatment resulted in the upregulation of BAX, downregulation of BCL-2, and elevation of caspase-3 cleavage in LNCaP cells. Notably, the epilupeol was a prominent compound in EADR as identified by GC-MS. Conclusion: The EADR exhibits anti-cancer activity against the LNCaP human prostate cancer cell line by inducing cytotoxicity and apoptosis. Our findings suggest that EADR promotes apoptosis by upregulating pro-apoptotic BAX, whereas downregulation of anti-apoptotic Bcl-2 results in the reduction of MMP and the activation of caspase-3. Of particular interest is the presence of epilupeol, a major compound identified in EADR, which may hold promise as a candidate for the development of therapeutic agents for prostate cancer.

Facile Fabrication of Titanium Carbide (Ti3C2)-Bismuth Vanadate (BiVO4) Nano-Coupled Oxides for Anti-cancer Activity.

Background MXene is a newly discovered substance consisting of 2D transition metal carbides or nitrides, produced through the disintegration and etching of aluminum layers. It possesses numerous properties, including a high surface area, conductivity, strength, stiffness, negative zeta potential, and excellent volumetric capacitance. MXene is utilized in detecting anti-cancer medicine, while bismuth vanadate (BiVO4) is synthesized to form an optimized material for anti-cancer activity applications. BiVO4 exhibits visible light absorption, strong chemical stability, and non-toxic properties. However, when loaded onto target stem cells, it can cause skin and respiratory irritation. Aim This study aimed to evaluate the facile fabrication of titanium carbide (Ti3C2)-BiVO4 nanomaterials coupled with oxides for anti-cancer activity. Moreover, it aimed to create Ti3C2-BiVO4 nanomaterials in combination with oxides using X-ray diffraction (XRD) and scanning electron microscopy (SEM) to assess their potential as efficient and targeted anti-cancer agents. Methods and materials To prepare the 2D Ti3C2 MXene, 2.5 g of titanium aluminum carbide (Ti3AlC2) powder was dissolved in 60 mL of a 40% hydrofluoric acid (HF) solution in a polytetrafluoroethylene(PTFE) container. The etching process was made more efficient and completed in 24 hours by using a magnetic stirring system to keep the mixture stirred and heated continuously. The centrifugation was performed at 4000 rpm for five minutes. Subsequently, deionized water was used to wash the solution many times until its pH reached around 7. The appropriate Ti3C2 powder was made by vacuum drying the acquired sediment at 80°C for 24 hours. Monoclinic BiVO4 samples were synthesized via a hydrothermal method. Typically, 10 mmol of Bi(NO3)3.5H2O was dissolved in 100 mL of a 2 mol/L HNO3 solution and stirred uniformly. Subsequently, 10 mmol of ammonium metavanadate (NH4VO3) was added to the mixed solution. After being stirred for one hour, the mixture was transferred into a 100 mL sealed Teflon-lined stainless steel autoclave at 180°C for 16 hours. After cooling to room temperature, the sediment was washed three times with deionized water, ethanol, and acetone, respectively. Finally, the suspension was dried at 80°C, followed by calcination at 450°C for three hours to obtain BiVO4. Ti3C2-BiVO4 heterostructures were prepared by surface modification Ti3C2 using BiVO4 suspensions by a simple, cost-effective approach. Results Ti3C2 nanosheets were observed with BiVO4 particles, and the high crystalline nature of the compound was confirmed after XRD analysis and energy-dispersive spectroscopy (EDS) analysis. The compound was found to be pure without any impurities and exhibited anti-cancer activity. Conclusion The XRD, field emission scanning electron microscopy(FESEM), and EDS investigations provide an in-depth analysis of the structural, morphological, and compositional characteristics of Ti3C2-BiVO4 sheets. The XRD analysis proves the successful combination of different materials and the presence of crystalline phases. The FESEM imaging technique exposes the shape and arrangement of particles in sheets, while the EDS analysis verifies the elemental composition and uniform distribution. These investigations show that Ti3C2-BiVO4 composites have been successfully synthesized, indicating their potential for use in anti-cancer applications.