Dissecting the antitumor effects of Scutellaria barbata: Initial insights into the metabolism of scutellarin and luteolin by gut microbiota.

The high prevalence of cancer and detrimental side effects associated with many cancer treatments necessitate the search for effective alternative therapies. Natural products are increasingly being recognized and investigated for their potential therapeutic benefits. Scutellaria barbata D. Don (SBD), a plant with potent antitumor properties, has attracted significant interest from oncology researchers. Its primary flavonoid components-scutellarin and luteolin-which have limited oral bioavailability due to poor absorption. This hinders its application for cancer treatment. The gut microbiota, which is considered a metabolic organ, can modulate the biotransformation of compounds, thereby altering their bioavailability and efficacy. In this study, we employed liquid chromatography tandem mass spectrometry (LC-MS/MS 8060) and ion trap-time of flight (LC-MSn-IT-TOF) analysis to investigate the ex vivo metabolism of scutellarin and luteolin by the gut microbiota. Five metabolites and one potential metabolite were identified. We summarized previous studies on their antitumor effects and performed in vitro tumor cell line studies to prove their antitumor activities. The possible key pathway of gut microbiota metabolism in vitro was validated using molecular docking and pure enzyme metabolic experiments. In addition, we explored the antitumor mechanisms of the two components of SBD through network pharmacology, providing a basis for subsequent target identification. These findings expand our understanding of the antitumor mechanisms of SBD. Notably, this study contributes to the existing body of knowledge regarding flavonoid biotransformation by the gut microbiota, highlighting the therapeutic potential of SBD in cancer treatment. Moreover, our results provide a theoretical basis for future in vivo pharmacokinetic studies, aiming to optimize the clinical efficacy of SBD in oncological applications.

Caspase-mediated AURKA cleavage at Asp132 is essential for paclitaxel to elicit cell apoptosis.

Background: Aurora kinase A (AURKA) is a potent oncogene that is often aberrantly expressed during tumorigenesis, and is associated with chemo-resistance in various malignancies. However, the role of AURKA in chemo-resistance remains largely elusive. Methods: The cleavage of AURKA upon viral infection or apoptosis stimuli was assesed by immunoblotting assays in several cancer cells or caspase deficient cell line models. The effect of AURKA cleavage at Asp132 on mitosis was explored by live cell imaging and immunofluorescence staining experiments. The role of Asp132-cleavage of AURKA induced by the chemotherapy drug paclitaxel was investigated using TUNEL, immunohistochemistry assay in mouse tumor xenograft model and patient tissues. Results: The proteolytic cleavage of AURKA at Asp132 commonly occurs in several cancer cell types, regardless of viral infection or apoptosis stimuli. Mechanistically, caspase 3/7/8 cleave AURKA at Asp132, and the Asp132-cleaved forms of AURKA promote cell apoptosis by disrupting centrosome formation and bipolar spindle assembly in metaphase during mitosis. The AURKAD132A mutation blocks the expression of cleaved caspase 3 and EGR1, which leads to reduced therapeutic effects of paclitaxel on colony formation and malignant growth of tumor cells in vitro and in vivo using a murine xenograft model and cancer patients. Conclusions: This study reveals that caspase-mediated AURKAD132 proteolysis is essential for paclitaxel to elicit cell apoptosis and indicates that AURKAD132 is a potential key target for chemotherapy.

Two spurge species, Euphorbia resinifera O. Berg and Euphorbia officinarum subsp. echinus (Hook.f. & Coss.) Vindt inhibit colon cancer.

BACKGROUND: Colon cancer, a prominent contributor to global cancer-related deaths, prompts the need for innovative treatment strategies. Euphorbia resinifera O. Berg (E. resinifera) and Euphorbia officinarum subsp. echinus Hook. f. & Coss Vindt (E. echinus) and their bee-derived products have been integral to traditional Moroccan medicine due to their potential health benefits. These plants have historical use in addressing various health issues, including cancer. However, their effects against colon cancer remain unclear, and the specific mechanisms underlying their anti-cancer effects lack comprehensive investigation. METHODS: The study aimed to assess the potential anti-cancer effects of Euphorbia extract on colon cancer cell lines (DLD-1) through various techniques. The apoptosis, migration, and proliferation of DLD-1 cells were measured in DLD-1 cells. In addition, we conducted High-Performance Liquid Chromatography (HPLC) analysis to identify the profile of phenolic compounds present in the studied extracts. RESULTS: The extracts demonstrated inhibition of colon cancer cell migration. E. resinifera flower and E. echinus stem extracts show significant anti-migratory effects. Regarding anti-proliferative activity, E. resinifera flower extract hindered proliferation, whereas E. echinus flower extract exhibited dose-dependent inhibition. Apoptosis assays revealed E. resinifera flower extract inducing early-stage apoptosis and E. echinus flower extract promoting late-stage apoptosis. While apoptotic protein expression indicated, E. resinifera stem and propolis extracts had minimal impact on apoptosis. CONCLUSION: The findings provide evidence supporting the beneficial effects of E resinifera and E. echinus extracts on colon cancer and exerting anti-cancer properties.

Lebanese cannabis oil as a potential treatment for acute myeloid leukemia: In vitro and in vivo evaluations.

ETHNOPHARMACOLOGICAL RELEVANCE: The Cannabis sativa L. ssp. indica (Lam.) plant has been historically utilized as a natural herbal remedy for the treatment of several ailments. In Lebanon, cannabis extracts have long been traditionally used to treat arthritis, diabetes, and cancer. AIM OF THE STUDY: The current study aims to investigate the anti-cancer properties of Lebanese cannabis oil extract (COE) on acute myeloid leukemia using WEHI-3 cells, and a WEHI-3-induced leukemia mouse model. MATERIALS AND METHODS: WEHI-3 cells were treated with increasing concentrations of COE to determine the IC50 after 24, 48 and 72-h post treatment. Flow cytometry was utilized to identify the mode of cell death. Western blot assay was performed to assess apoptotic marker proteins. In vivo model was established by inoculating WEHI-3 cells in BALB/c mice, and treatment commencing 10 days post-inoculation and continued for a duration of 3 weeks. RESULTS: COE exhibited significant cytotoxicity with IC50 of 7.76, 3.82, and 3.34 µg/mL at 24, 48, and 72 h respectively post-treatment. COE treatment caused an induction of apoptosis through an inhibition of the MAPK/ERK pathway and triggering a caspase-dependent apoptosis via the extrinsic and intrinsic modes independent of ROS production. Animals treated with COE exhibited a significantly higher survival rate, reduction in spleen weight as well as white blood cells count. CONCLUSION: COE exhibited a potent anti-cancer activity against AML cells, both in vitro and in vivo. These findings emphasize the potential application of COE as a chemotherapeutic adjuvant in treatment of acute myeloid leukemia.

Comprehensive Characterization of Phytochemical Composition, Membrane Permeability, and Antiproliferative Activity of Juglans nigra Polyphenols.

The aim of our study was the detailed polyphenol profiling of Juglans nigra and the characterization of the membrane permeability and antiproliferative properties of its main phenolics. A total of 161 compounds were tentatively identified in J. nigra bark, leaf, and pericarp extracts by ultrahigh-performance liquid chromatography-high-resolution tandem mass spectrometry (UHPLC-HR-MS/MS). Eight compounds including myricetin-3-O-rhamnoside (86), quercetin-3-O-rhamnoside (106), quercetin-3-O-xyloside (74), juglone (141), 1,2,3,4-tetrahydro-7,8-dihydroxy-4-oxonaphthalen-1-yl-6-O-galloyl-glucoside (92), ellagic acid (143), gallic acid (14), and ethyl gallate (58) were isolated from J. nigra pericarp. The in vitro antiproliferative activity of the isolated compounds was investigated against three human cancer cell lines, confirming that juglone (141) inhibits cell proliferation in all of them, and has similar activity as the clinical standards. The permeability of the isolated compounds across biological membranes was evaluated by the parallel artificial membrane permeability assay (PAMPA). Both juglone (141) and ethyl-gallate (58) showed positive results in the blood-brain-barrier-specific PAMPA-BBB study. Juglone (141) also possesses logPe values which indicates that it may be able to cross both the GI and BBB membranes via passive diffusion.

Pretreatment of Melanoma Cells with Aqueous Ethanol Extract from Madhuca longifolia Bark Strongly Potentiates the Activity of a Low Dose of Dacarbazine.

Madhuca longifolia is an evergreen tree distributed in India, Nepal, and Sri Lanka. This tree is commonly known as Mahua and is used in traditional medicine. It was demonstrated that ethanol extract from the bark of M. longifolia possessed potent cytotoxic activity towards two melanoma cell lines, in contrast to aqueous extract that exhibited no activity. Apart from being selectively cytotoxic to cancer cells (with no activity towards non-cancerous fibroblasts), the studied extract induced apoptosis and increased reactive oxygen species generation in melanoma cells. Additionally, the use of the extract together with dacarbazine (both in non-toxic concentrations) resulted in the enhancement of their anticancer activity. Moreover, the pretreatment of melanoma cells with M. longifolia extract potentiated the activity of a low dose of dacarbazine to an even higher extent. It was concluded that ethanol extract of M. longifolia sensitized human melanoma cells to chemotherapeutic drugs. It can therefore be interesting as a promising source of compounds for prospective combination therapy.

Urtica dioica: Anticancer Properties and Other Systemic Health Benefits from In Vitro to Clinical Trials.

While conventional medicine has advanced in recent years, there are still concerns about its potential adverse reactions. The ethnopharmacological knowledge established over many centuries and the existence of a variety of metabolites have made medicinal plants, such as the stinging nettle plant, an invaluable resource for treating a wide range of health conditions, considering its minimal adverse effects on human health. The aim of this review is to highlight the therapeutic benefits and biological activities of the edible Urtica dioica (UD) plant with an emphasis on its selective chemo-preventive properties against various types of cancer, whereby we decipher the mechanism of action of UD on various cancers including prostate, breast, leukemia, and colon in addition to evaluating its antidiabetic, microbial, and inflammatory properties. We further highlight the systemic protective effects of UD on the liver, reproductive, excretory, cardiovascular, nervous, and digestive systems. We present a critical assessment of the results obtained from in vitro and in vivo studies as well as clinical trials to highlight the gaps that require further exploration for future prospective studies.

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.

Efficacy of Hyperthermic Pressurized Intraperitoneal Aerosol Chemotherapy in an In Vitro Model Using a Human Gastric Cancer AGS Cell Line and an Abdominal Cavity Model.

PURPOSE: Peritoneal carcinomatosis (PC) presents a major challenge in the treatment of late-stage, solid tumors, with traditional therapies limited by poor drug penetration. We evaluated a novel hyperthermic pressurized intraperitoneal aerosol chemotherapy (HPIPAC) system using a human abdominal cavity model for its efficacy against AGS gastric cancer cells. MATERIALS AND METHODS: A model simulating the human abdominal cavity and AGS gastric cancer cell line cultured dishes were used to assess the efficacy of the HPIPAC system. Cell viability was measured to evaluate the impact of HPIPAC under 6 different conditions: heat alone, PIPAC with paclitaxel (PTX), PTX alone, normal saline (NS) alone, heat with NS, and HPIPAC with PTX. RESULTS: Results showed a significant reduction in cell viability with HPIPAC combined with PTX, indicating enhanced cytotoxic effects. Immediately after treatment, the average cell viability was 66.6%, which decreased to 49.2% after 48 hours and to a further 19.6% after 120 hours of incubation, demonstrating the sustained efficacy of the treatment. In contrast, control groups exhibited a recovery in cell viability; heat alone showed cell viability increasing from 90.8% to 94.4%, PIPAC with PTX from 82.7% to 89.7%, PTX only from 73.3% to 74.8%, NS only from 90.9% to 98.3%, and heat with NS from 74.4% to 84.7%. CONCLUSIONS: The HPIPAC system with PTX exhibits a promising approach in the treatment of PC in gastric cancer, significantly reducing cell viability. Despite certain limitations, this study highlights the system's potential to enhance treatment outcomes. Future efforts should focus on refining HPIPAC and validating its effectiveness in clinical settings.

Isolation, Characterization, and Antiproliferative Activity of Terpenoids from the Tropical Plant Turraea delphinensis.

The isolation, structure determination, and biological evaluation of constituents from the organic extract of Turraea delphinensis Wahlert (Meliaceae) resulted in the isolation of 51 secondary metabolites, including 14 new terpenoids (six cycloartanes, four tirucallanes/euphanes, three limonoids, and a 7-keto sterol). Among the new compounds, 1 is the first triterpenoid with a trioxaspiro[4.4]nonane side chain, while 11-13 are the first 17-γ-lactone tetranortriterpenoids with four oxygenated functional groups at C-1, -3, -6, and -7. The isolated compounds were evaluated for antiproliferative activity against five human tumor cell lines, including a vinblastine-resistant cell line.

Luteolin enhances drug chemosensitivity by downregulating the FAK/PI3K/AKT pathway in paclitaxel­resistant esophageal squamous cell carcinoma.

Drug resistance is a key factor underlying the failure of tumor chemotherapy. It enhances the stem­like cell properties of cancer cells, tumor metastasis and relapse. Luteolin is a natural flavonoid with strong anti­tumor effects. However, the mechanism(s) by which luteolin protects against paclitaxel (PTX)­resistant cancer cell remains to be elucidated. The inhibitory effect of luteolin on the proliferation of EC1/PTX and EC1 cells was detected by cell counting kit­8 assay. Colony formation and flow cytometry assays were used to assess clonogenic capacity, cell cycle and apoptosis. Wound healing and Transwell invasion tests were used to investigate the effects of luteolin on the migration and invasion of EC1/PTX cells. Western blotting was used to detect the protein levels of EMT­related proteins and stem cell markers after sphere formation. Parental cells and drug­resistant cells were screened by high­throughput sequencing to detect the differential expression of RNA and differential genes. ELISA and western blotting were used to verify the screened PI3K/Akt signaling pathway, key proteins of which were explored by molecular docking. Hematoxylin and eosin staining and TUNEL staining were used to observe tumor xenografts on morphology and apoptosis in nude mice. The present study found that luteolin inhibited tumor resistance (inhibited proliferation, induced cell cycle arrest and apoptosis and hindered migration invasion, EMT and stem cell spherification) in vitro in PTX­resistant esophageal squamous cell carcinoma (ESCC) cells. In addition, luteolin enhanced drug sensitivity and promoted the apoptosis of drug­resistant ESCC cells in combination with PTX. Mechanistically, luteolin may inhibit the PI3K/AKT signaling pathway by binding to the active sites of focal adhesion kinase (FAK), Src and AKT. Notably, luteolin lowered the tumorigenic potential of PTX­resistant ESCC cells but did not show significant toxicity in vivo. Luteolin enhanced drug chemosensitivity by downregulating the FAK/PI3K/AKT pathway in PTX­resistant ESCC and could be a promising agent for the treatment of PTX­resistant ESCC cancers.

[Chemical constituents from Clitocybe clavipes and their antitumor activities].

This paper aimed to study the chemical constituents from Clitocybe clavipes. Silica gel, ODS, Sephadex LH-20, and semi-p reparative HPLC were employed to separate the ethanol extract of C. clavipes. Six compounds were identified by ~1H-NMR, ~(13)CNMR,and ESI-MS as clavilactone L(1), clavilactone A(2), clavilactone B(3), clavilactone E(4), clavilactone H(5), and clav ilactone I(6). Among them, compound 1 was a new meroterpenoid with a 10-membered carbocycle connected to a hydroquinone. Theantitumor activities of compounds 1-6 were determined by the methyl thiazolyl tetrazolium(MTT) ass ay. The results showed that compounds 1-6 exerted inhibitory effects on the proliferation of human gastric cancer cells(MGC-803),human non-small cell lung cancer cells(A549), and cervical cancer cells(HeLa). Compound 1 exhibited significant inhibitory activity against MGC-803 cells, with the half maximal inhibitory concentration(IC_(50)) of 11. 76 µmol·L~(-1).

Kalanchoe pinnata (Lam.) Pers. Leaf ethanolic extract exerts selective anticancer activity through ROS-induced apoptotic cell death in human cancer cell lines.

BACKGROUND: The leaves of Kalanchoe pinnata (Lam.) Pers. (K. pinnata), a succulent plant native to tropical regions, are used as a medicinal alternative against cancer in several countries worldwide; however, its therapeutic potential to fight cancer has been little addressed. In this study, we analyzed the phytochemical content, antioxidant capacity, and selectivity of K. pinnata leaf ethanolic extract against different human cancer cell lines in vitro. METHODOLOGY: This study subjected the ethanolic extract to enzymatic assays to quantify the phytochemical content (phenolics, flavonoids, and anthraquinones) and its radical scavenging and iron-reducing capacities. Also, the phytoconstituents and major phenolic compounds present in the extract's subfractions were identified by GC-MS, HPLC, and NMR. Human cancer (MCF-7, PC-3, HT-29) and normal colon (CoN) cell lines were treated with different concentrations of K. pinnata leaf ethanolic extract, and the changes in cell proliferation (sulforhodamine B assay), caspases activity (FITC-VAD-FMK reporter), mitochondrial membrane potential (MMP, rhodamine 123 assay), chromatin condensation/fragmentation (Hoechst 33342 stain), and ROS generation (DCFH2 probe assay) were assessed. RESULTS: The results showed that the K. pinnata leaf ethanolic extract is rich in phytoconstituents with therapeutic potential, including phenols (quercetin and kaempferol), flavonoids, fatty acid esters (34.6% of the total composition), 1- triacontanol and sterols (ergosterol and stigmasterol, 15.4% of the total composition); however, it presents a poor content of antioxidant molecules (IC50 = 27.6 mg/mL for H2O2 scavenging activity vs. 2.86 mg/mL in the case of Trolox). Notably, the extract inhibited cell proliferation and reduced MMP in all human cell lines tested but showed selectivity for HT-29 colon cancer cells compared to CoN normal cells (SI = 8.4). Furthermore, ROS generation, caspase activity, and chromatin condensation/fragmentation were augmented significantly in cancer-derived cell lines, indicating a selective cytotoxic effect. CONCLUSION: These findings reveal that the K. pinnata leaf ethanolic extract contains several bioactive molecules with therapeutic potential, capable of displaying selective cytotoxicity in different human cancer cell lines.

Alantolactone Induced Apoptosis and DNA Damage of Cervical Cancer through ATM/CHK2 Signaling Pathway.

Traditional Chinese Medicine, known for its minimal side effects and significant clinical efficacy, has attracted considerable interest for its potential in cancer therapy. In particular, Inula helenium L. has demonstrated effectiveness in inhibiting a variety of cancers. This study focuses on alantolactone (ALT), a prominent compound from Inula helenium L., recognized for its anti-cancer capabilities across multiple cancer types. The primary objective of this study is to examine the influence of ALT on the proliferation, apoptosis, cell cycle, and tumor growth of cervical cancer (CC) cells, along with its associated signaling pathways. To determine protein expression alterations, Western blot analysis was conducted. Furthermore, an in vivo model was created by subcutaneously injecting HeLa cells into nude mice to assess the impact of ALT on cervical cancer. Our research thoroughly investigates the anti-tumor potential of ALT in the context of CC. ALT was found to inhibit cell proliferation and induce apoptosis in SiHa and HeLa cell lines, particularly targeting ataxia-telangiectasia mutated (ATM) proteins associated with DNA damage. The suppression of DNA damage and apoptosis induction when ATM was inhibited underscores the crucial role of the ATM/cell cycle checkpoint kinase 2 (CHK2) axis in ALT's anti-tumor effects. In vivo studies with a xenograft mouse model further validated ALT's effectiveness in reducing CC tumor growth and promoting apoptosis. This study offers new insights into how ALT combats CC, highlighting its promise as an effective anti-cervical cancer agent and providing hope for improved treatment outcomes for CC patients.

IL-6 Inhibitory Compounds from the Aerial Parts of Piper attenuatum and Their Anticancer Activities on Ovarian Cancer Cell Lines.

Piper attenuatum Buch-Ham, a perennial woody vine belonging to the Piperaceae family, is traditionally used in Southeast Asia for treating various ailments such as malaria, headache, and hepatitis. This study described the isolation and identification of three new compounds, piperamides I-III (1-3), which belong to the maleimide-type alkaloid skeletons, along with fifteen known compounds (4-18) from the methanol extract of the aerial parts of P. attnuatum. Their chemical structures were elucidated using spectroscopic methods (UV, IR, ESI-Q-TOF-MS, and 1D/2D NMR). All the isolates were evaluated for their ability to inhibit IL-6 activity in the human embryonic kidney-Blue™ IL-6 cell line and their cytotoxic activity against ovarian cancer cell lines (SKOV3/SKOV3-TR) and chemotherapy-resistant variants (cisplatin-resistant A2780/paclitaxel-resistant SKOV3). The compounds 3, 4, 11, 12, 17, and 18 exhibited IL-6 inhibition comparable to that of the positive control bazedoxifene. Notably, compound 12 displayed the most potent anticancer effect against all the tested cancer cell lines. These findings highlight the importance of researching the diverse activities of both known and newly discovered natural products to fully unlock their potential therapeutic benefits.

Isovaleryl Sucrose Esters from Atractylodes japonica and Their Cytotoxic Activity.

Cancer represents one of the most significant health challenges currently facing humanity, and plant-derived antitumour drugs represent a prominent class of anticancer medications in clinical practice. Isovaleryl sucrose esters, which are natural constituents, have been identified as having potential antitumour effects. However, the mechanism of action remains unclear. In this study, 12 isovaleryl sucrose ester components, including five new (1-5) and seven known compounds (6-12), were isolated from the roots of Atractylodes japonica. The structures of the compounds were elucidated using 1D and 2D-NMR spectroscopy, complemented by HR-ESI-MS mass spectrometry. The cytotoxic activities of all the compounds against human colon cancer cells (HCT-116) and human lung adenocarcinoma cells (A549) were also evaluated using the CCK8 assay. The results demonstrated that compounds 2, 4, and 6 were moderately inhibitory to HCT-116 cells, with IC50 values of 7.49 ± 0.48, 9.03 ± 0.21, and 13.49 ± 1.45 µM, respectively. Compounds 1 and 6 were moderately inhibitory to A549, with IC50 values of 8.36 ± 0.77 and 7.10 ± 0.52 µM, respectively. Molecular docking revealed that compounds 1-9 exhibited a stronger affinity for FGFR3 and BRAF, with binding energies below -7 kcal/mol. Compound 2 exhibited the lowest binding energy of -10.63 kcal/mol to FGFR3. We screened the compounds with lower binding energies, and the protein-ligand complexes already obtained after molecular docking were subjected to exhaustive molecular dynamics simulation experiments, which simulated the dynamic behaviour of the molecules in close proximity to the actual biological environment, thus providing a deeper understanding of their functions and interaction mechanisms. The present study provides a reference for the development and use of iso-valeryl sucrose esters in the antitumour field.

Targeting the pancreatic tumor microenvironment by plant-derived products and their nanoformulations.

Pancreatic cancer remains a significant health issue with limited treatment options. The tumor stroma, a complex environment made up of different cells and proteins, plays a crucial role in tumor growth and chemoresistance. Targeting tumor stroma, consisting of diverse non-tumor cells such as fibroblasts, extracellular matrix (ECM), immune cells, and also pre-vascular cells is encouraging for remodeling solid cancers, such as pancreatic cancer. Remodeling the stroma of pancreas tumors can be suggested as a strategy for reducing resistance to chemo/immunotherapy. Several studies have shown that phytochemicals from plants can affect the tumor environment and have anti-cancer properties. By targeting key pathways involved in stromal activation, phytochemicals may disrupt communication between the tumor and stroma and make tumor cells more sensitive to different treatments. Additionally, phytochemicals have immunomodulatory and anti-angiogenic properties, all of which contribute to their potential in treating pancreatic cancer. This review will provide a detailed look at how phytochemicals impact the tumor stroma and their effects on pancreatic tumor growth, spread, and response to treatment. It will also explore the potential of combining phytochemicals with other treatment options like chemotherapy, immunotherapy, and radiation.

Anticancer effects of Artemisia campestris extract on acute myeloid leukemia cells: an ex vivo study.

Cure rates for acute myeloid leukemia (AML) remain suboptimal; thus, new treatment strategies are needed for this deadly disease. Artemisia campestris leaves hold significant value in traditional medicine. Despite extensive research conducted on this plant globally, the specific anti-AML properties of the leaves have received limited investigation. This study aims to explore the potential anti-leukemic activities of the ethyl acetate extract derived from Artemisia campestris (EAEAC), using mononuclear cells from bone marrow of thirteen AML patients. To this end, cytotoxic effects were evaluated using the MTT assay, and the mechanisms of cell death were investigated through various methods, including propidium iodide staining, annexin V/propidium iodide double staining, mitochondrial depolarization, and caspase-3/7 activation assays. Results demonstrated that EAEAC induced cell apoptosis by increasing DNA fragmentation, causing mitochondrial depolarization, and activating caspases 3/7. On the other hand, we assessed EAEAC's effect on two leukemia stem cell subpopulations, with results suggesting a potential decrease in their frequencies (three/five patients).

The flavonoids from the fruits of Psoralea corylifolia and their potential in inhibiting metastasis of human non-small cell lung cancers.

Nineteen flavonoids were isolated from the fruits of Psoralea corylifolia L., including a novel flavanol (3) and three novel isoflavones (12-14). Their chemical structures were unequivocally determined through comprehensive spectral data analysis. The anti-proliferative effect of the isolated flavonoids was assessed in vitro using the MTT assay. Molecular docking and ELISA were employed to determine the inhibitory effects of the active compounds on ALK5. Isobavachalcone was found to inhibit TGF-ß1 induced EMT in A549 cells by Wound healing assay and Transwell chamber assay. Immunofluorescence assay and Western blot assay showed that IBC could inhibit cytoskeleton rearrangement, reduce the phosphorylation of ALK5, ERK, and Smad, down-regulate Snail expression, and up-regulate E-cadherin expression in TGF-ß1 induced A549 cells, thereby exerting the potential inhibitory effects on epithelial-mesenchymal transition (EMT) process in A549 cells. The findings presented herein establish a fundamental basis for investigating the anti-proliferative and anti-metastatic properties of psoralen flavonoids in human non-small cell lung cancer.

Carnosic acid: an effective phenolic diterpenoid for prevention and management of cancers via targeting multiple signaling pathways.

Cancer is a serious global public health issue, and a great deal of research has been made to treat cancer. Of these, discovery of promising compounds that effectively fight cancer always has been the main point of interest in pharmaceutical research. Carnosic acid (CA) is a phenolic diterpenoid compound widely present in Lamiaceae plants such as Rosemary (Rosmarinus officinalis L.). In recent years, there has been increasing evidence that CA has significant anti-cancer activity, such as leukaemia, colorectal cancer, breast cancer, lung cancer, liver cancer, pancreatic cancer, stomach cancer, lymphoma, prostate cancer, oral cancer, etc. The potential mechanisms involved by CA, including inhibiting cell proliferation, inhibiting metastasis, inducing cell apoptosis, stimulating autophagy, regulating the immune system, reducing inflammation, regulating the gut microbiota, and enhancing the effects of other anti-cancer drugs. This article reviews the biosynthesis, pharmacokinetics and metabolism, safety and toxicity, as well as the molecular mechanisms and signaling pathways of the anticancer activity of CA. This will contribute to the development of CA or CA-containing functional foods for the prevention and treatment of cancer, providing important advances in the advancement of cancer treatment strategies.