Antiproliferative Activity Research Articles

1,3,4-Oxadiazole as an Anticancer Agent

The modern era's fastest-growing disease is cancer, it poses a serious threat to people's lives. For the treatment of various cancers, the FDA has approved a number of medications. However, because of the rise in drug toxicity incidents, there is a continual need for the discovery of novel anti-cancer drugs. Five-membered heterocyclic ring with multifaceted biological action is the 1,3,4-oxadiazole. Their anti-proliferative actions are linked to a number of processes, including the inhibition of kinases, enzymes, and growth factors. Numerous 1,3,4-oxadiazoles have been found to be effective anticancer agents for a variety of cancer cell types. Oxadiazoles may target the NF-kB signalling system to exert their anti-cancer effects, according to certain reports. This study examines the importance of the 1,3,4-oxadiazole ring structure and how it can function as a model for a new anticancer drug. This in-depth analysis focuses on the research on 1,3,4-oxadiazole as a cancer preventative.

Phosphatidylcholine and ceramide derivatives from white rot fungus Microporus xanthropus PP17-20

The undescribed phosphatidylcholine (1), along with twelve known compounds, was isolated from the cultures of white rot fungus Microporus xanthropus PP17-20. In this work the fungus was cultivated in Yeast-Malt extract medium to explore active compound production. The chemical structures were elucidated on the basis of spectroscopic and HRESIMS data. Several isolated compounds were evaluated for anti-proliferative activity against A549 and MCF-7 cancer cell lines.

PH-Sensitive doxorubicin delivery using zinc oxide nanoparticles as a rectified theranostic platform: in vitro anti-proliferative, apoptotic, cell cycle arrest and in vivo radio-distribution studies.

Despite enormous advancements in its management, cancer is the world's primary cause of mortality. Therefore, tremendous strides were made to produce intelligent theranostics with mitigated side effects and improved specificity and efficiency. Thus, we developed a pH-sensitive theranostic platform composed of dextran immobilized zinc oxide nanoparticles, loaded with doxorubicin and radiolabeled with the technetium-99m radionuclide (99mTc-labelled DOX-loaded ZnO@dextran). The platform measured 11.5 nm in diameter with -12 mV zeta potential, 88% DOX loading efficiency and 98.5% radiolabeling efficiency. It showed DOX release in a pH-responsive manner, releasing 93.1% cumulatively at pH 5 but just 7% at pH 7.4. It showed improved intracellular uptake, which resulted in a high growth suppressive effect against MCF-7 cancer cells as compared to the free DOX. It boasted a 4 times lower IC50 than DOX, indicating its significant anti-proliferative potential (0.14 and 0.55 μg ml-1, respectively). The in vitro biological evaluation revealed that its molecular mode of anti-proliferative action included downregulating Cdk-2, which provoked G1/S cell cycle arrest, and upregulating both the intracellular ROS level and caspase-3, which induced apoptosis and necrosis. The in vivo experiments in Ehrlich-ascites carcinoma bearing mice demonstrated that DOX-loaded ZnO@dextran showed a considerable 4-fold increase in anti-tumor efficacy compared to DOX. Moreover, by utilizing the diagnostic radionuclide (99mTc), the radiolabeled platform (99mTc-labelled DOX-loaded ZnO@dextran) was in vivo monitored in tumor-bearing mice, revealing high tumor accumulation (14% ID g-1 at 1 h p.i.) and reduced uptake in non-target organs with a 17.5 T/NT ratio at 1 h p.i. Hence, 99mTc-labelled DOX-loaded ZnO@dextran could be recommended as a rectified tumor-targeted theranostic platform.

Benzofuran-2-Carboxamide Derivatives as Immunomodulatory Agents Blocking the CCL20-Induced Chemotaxis and Colon Cancer Growth.

The correlation between the CCL20/CCR6 axis and autoimmune and non-autoimmune disorders is widely recognized. Inhibition of the CCL20-dependent cell migration represents therefore a promising approach for the treatment of many diseases, such as inflammatory bowel diseases and colorectal cancer. We report herein our efforts to explore the biologically relevant chemical space around the benzofuran scaffold of MR120, a modulator of the CCL20/CCR6 axis previously discovered by our group. A functional screening allowed us to identify C4 and C5-substituted derivatives as the most effective inhibitors of the CCL20-induced chemotaxis of human peripheral blood mononuclear cells (PBMC). Moreover, selected compounds (16 e and 24 b) also proved to potently inhibit the growth of different colon cancer cell lines, with cytotoxic/cytostatic and antiproliferative activity.

Steroidal scaffold decorations in Solanum alkaloid biosynthesis

Steroidal glycoalkaloids (SGAs) are specialized metabolites produced by hundreds of Solanum species, including important vegetable crops such as tomato, potato, and eggplant. Although it has been known that SGAs play important roles in defense in plants and “anti-nutritional” effects (e.g., toxicity and bitterness) to humans, many of these molecules have documented anti-cancer, anti-microbial, anti-inflammatory, anti-viral, and anti-pyretic activities. Among these, α-solasonine and α-solamargine isolated from black nightshade (Solanum nigrum) are reported to have potent anti-tumor, anti-proliferative, and anti-inflammatory activities. Notably, α-solasonine and α-solamargine, along with the core steroidal aglycone solasodine, are the most widespread SGAs produced among the Solanum plants. However, it is still unknown how plants synthesize these bioactive steroidal molecules. Through comparative metabolomic-transcriptome-guided approach, biosynthetic logic, combinatorial expression in Nicotiana benthamiana, and functional recombinant enzyme assays, here we report the discovery of 12 enzymes from S. nigrum that converts the starting cholesterol precursor to solasodine aglycone, and the downstream α-solasonine, α-solamargine, and malonyl-solamargine SGA products. We further identified six enzymes from cultivated eggplant that catalyze the production of α-solasonine, α-solamargine, and malonyl-solamargine SGAs from solasodine aglycone via glycosylation and atypical malonylation decorations. Our work provides the gene tool box and platform for engineering the production of high-value, steroidal bioactive molecules in heterologous hosts using synthetic biology.

Synthesis and stabilization of anatase form of biomimetic TiO2 nanoparticles for enhancing anti-tumor potential

Abstract The present study emphasizes the stabilization of the biologically active anatase form of titanium dioxide (TiO2) nanoparticles (NP). TiO2 NP require stringent conditions for chemical synthesis and are usually a mixture of biologically inactive bulk rutile and the active bulk anatase forms. We utilized the culture pellet of the Exiguobacterium aestuarii SBG4 MH185868 to synthesize and stabilize the anatase form of TiO2 NP. The NP showed λ max at ∼350 nm and scanning electron microscope micrographs indicated their oval and spherical shape. Steric stabilized anatase TiO2 NP exhibited substantial cytotoxicity of up to 80% reduction in cell viability at 100 µg against cervical cancer derived HeLa and SiHa cell lines, whereas the rutile form showed least cytotoxicity. Clonogenic inhibition assay of HeLa cells showed dose-dependent decline with a 75% reduction in colony formation at 100 µg TiO2 NP and cell migration assay revealed significant inhibition in recovery of the wound/scratch in presence of anatase form of TiO2 NP (10–33% at 24 h and 42–79% at 48 h). Co-incubation of HeLa cells with anatase TiO2 NP in chorioallantoic membrane of embryonated chick eggs prevented the formation of new capillaries (20 ± 5% compared with control groups), indicating appreciable anti-angiogenic activity of the NP. Further, TiO2 NP tagged with doxorubicin and paclitaxel exhibited enhanced cytotoxicity against cancer cells at very low concentrations of 9 and 120 nM itself, indicating their anti-tumor potential. In conclusion, biomimetic anatase TiO2 NP have significant anti-proliferative and anti-angiogenic activity and can have potential application in tagging with generic anti-cancer drugs for enhanced cytotoxicity against cancer cells.

Antiproliferative effect of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues on IL-6 mediated STAT3 and role of the apoptotic pathway in albino Wistar rats of ethyl carbamate-induced lung carcinoma: In-silico, In-vitro, and In-vivo study

Lung cancer (LC) ranks second most prevalent cancer in females after breast cancer and second in males after prostate cancer. Based on the GLOBOCAN 2020 report, India represented 5.9% of LC cases and 8.1% of deaths caused by the disease. Several clinical studies have shown that LC occurs because of biological and morphological abnormalities and the involvement of altered level of antioxidants, cytokines, and apoptotic markers. In the present study, we explored the antiproliferative activity of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues against LC using in-vitro, in-silico, and in-vivo models. In-vitro screening against A549 cells revealed compounds 9B (8-methoxy-5-(3,4,5-trimethoxyphenyl)-5,6-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidine) and 12B (5-(4-chlorophenyl)-5,6-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidine) as potential pyrimidine analogues against LC. Compounds 9B and 12B were docked with different molecular targets IL-6, Cyt-C, Caspase9, and Caspase3 using AutoDock Vina 4.1 to evaluate the binding affinity. Subsequently, in-vivo studies were conducted in albino Wistar rats through ethyl-carbamate (EC)- induced LC. 9B and 12B imparted significant effects on physiological (weight variation), and biochemical (anti-oxidant [TBAR’s, SOD, ProC, and GSH), lipid (TC, TG, LDL, VLDL, and HDL)], and cytokine (IL-2, IL-6, IL-10, and IL-1β) markers in EC-induced LC in albino Wistar rats. Morphological examination (SEM and H&E) and western blotting (IL-6, STAT3, Cyt-C, BAX, Bcl-2, Caspase3, and caspase9) showed that compounds 9B and 12B had antiproliferative effects. Accordingly, from the in-vitro, in-silico, and in-vivo experimental findings, we concluded that 9B and 12B have significant antiproliferative potential and are potential candidates for further evaluation to meet the requirements of investigation of new drug application.

Impact of Simulated Human Gastrointestinal Digestion on the Functional Properties of Dietary Fibres Obtained from Broccoli Leaves, Grape Stems, Pomegranate and Tomato Peels.

This study aimed to analyse the impact of a simulated human digestion process on the composition and functional properties of dietary fibres derived from pomegranate-peel, tomato-peel, broccoli-stem and grape-stem by-products. For this purpose, a computer-controlled simulated digestion system consisting of three bioreactors (simulating the stomach, small intestine and colon) was utilised. Non-extractable phenols associated with dietary fibre and their influence on antioxidant capacity and antiproliferative activity were investigated throughout the simulated digestive phases. Additionally, the modifications in oligosaccharide composition, the microbiological population and short-chain fatty acids produced within the digestion media were examined. The type and composition of each dietary fibre significantly influenced its functional properties and behaviour during intestinal transit. Notably, the dietary fibre from the pomegranate peel retained its high phenol content throughout colon digestion, potentially enhancing intestinal health due to its strong antioxidant activity. Similarly, the dietary fibre from broccoli stems and pomegranate peel demonstrated anti-proliferative effects in both the small and the large intestines, prompting significant modifications in colonic microbiology. Moreover, these fibre types promoted the growth of bifidobacteria over lactic acid bacteria. Thus, these results suggest that the dietary fibre from pomegranate peel seems to be a promising functional food ingredient for improving human health.

RNase H-sensitive multifunctional ASO-based constructs as promising tools for the treatment of multifactorial complex pathologies

Combined therapies play a key role in the fight against complex pathologies, such as cancer and related drug-resistance issues. This is particularly relevant in targeted therapies where inhibition of the drug target can be overcome by cross-activating complementary pathways. Unfortunately, the drug combinations approved to date –mostly based on small molecules– face several problems such as toxicity effects, which limit their clinical use. To address these issues, we have designed a new class of RNase H-sensitive construct (3ASO) that can be disassembled intracellularly upon cell entry, leading to the simultaneous release of three different therapeutic oligonucleotides (ONs), tackling each of them the mRNA of a different protein. Here, we used Escherichia coli RNase H1 as a model to study an unprecedented mode of recognition and cleavage, that is mainly dictated by the topology of our RNA·DNA-based hybrid construct. As a model system for our technology we have created 3ASO constructs designed to specifically inhibit the expression of HER2, Akt and Hsp27 in HER2+ breast cancer cells. These trifunctional ON tools displayed very low toxicity and good levels of antiproliferative activity in HER2+ breast cancer cells. The present study will be of great potential in the fight against complex pathologies involving multiple mRNA targets, as the proposed cleavable designs will allow the efficient single-dose administration of different ON drugs simultaneously.

Structure-Activity Relationship Study of Tris-Benzamides as Estrogen Receptor Coregulator Binding Modulators.

Estrogen receptor coregulator binding modulators (ERXs) are a novel class of molecules targeting the interaction between estrogen receptor α (ERα) and its coregulator proteins, which has proven to be an attractive strategy for overcoming endocrine resistance in breast cancer. We previously reported ERX-11, an orally bioavailable tris-benzamide, that demonstrated promising antitumor activity against ERα-positive breast cancer cells. To comprehend the significance of the substituents in ERX-11, we carried out structure-activity relationship studies. In addition, we introduced additional alkyl substituents at either the N- or C-terminus to improve binding affinity and biological activity. Further optimization guided by conformational restriction led to the identification of a trans-4-phenylcyclcohexyl group at the C-terminus (18h), resulting in a greater than 10-fold increase in binding affinity and cell growth inhibition potency compared to ERX-11. Tris-benzamide 18h disrupted the ERα-coregulator interaction and inhibited the ERα-mediated transcriptional activity. It demonstrated strong antiproliferative activity on ERα-positive breast cancer cells both in vitro and in vivo, offering a promising potential as a therapeutic candidate for treating ERα-positive breast cancer.

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.

Preclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) in KMT2A- and NPM1-altered leukemias

AbstractThe interaction between menin and histone-lysine N-methyltransferase 2A (KMT2A) is a critical dependency for KMT2A- or nucleophosmin 1 (NPM1)–altered leukemias and an emerging opportunity for therapeutic development. JNJ-75276617 (bleximenib) is a novel, orally bioavailable, potent, and selective protein-protein interaction inhibitor of the binding between menin and KMT2A. In KMT2A-rearranged (KMT2A-r) and NPM1-mutant (NPM1c) acute myeloid leukemia (AML) cells, JNJ-75276617 inhibited the association of the menin-KMT2A complex with chromatin at target gene promoters, resulting in reduced expression of several menin-KMT2A target genes, including MEIS1 and FLT3. JNJ-75276617 displayed potent antiproliferative activity across several AML and acute lymphoblastic leukemia (ALL) cell lines and patient samples harboring KMT2A or NPM1 alterations in vitro. In xenograft models of AML and ALL, JNJ-75276617 reduced leukemic burden and provided a significant dose-dependent survival benefit accompanied by expression changes of menin-KMT2A target genes. JNJ-75276617 demonstrated synergistic effects with gilteritinib in vitro in AML cells harboring KMT2A-r. JNJ-75276617 further exhibited synergistic effects with venetoclax and azacitidine in AML cells bearing KMT2A-r in vitro, and significantly increased survival in mice. Interestingly, JNJ-75276617 showed potent antiproliferative activity in cell lines engineered with recently discovered mutations (MEN1M327I or MEN1T349M) that developed in patients refractory to the menin-KMT2A inhibitor revumenib. A cocrystal structure of menin in complex with JNJ-75276617 indicates a unique binding mode distinct from other menin-KMT2A inhibitors, including revumenib. JNJ-75276617 is being clinically investigated for acute leukemias harboring KMT2A or NPM1 alterations, as a monotherapy for relapsed/refractory acute leukemia (NCT04811560), or in combination with AML-directed therapies (NCT05453903).

Targeting Unique Ligand Binding Domain Structural Features Downregulates DKK1 in Y537S ESR1 Mutant Breast Cancer Cells.

Resistance to endocrine therapies remains a major clinical hurdle in breast cancer. Mutations to estrogen receptor alpha (ERα) arise after continued therapeutic pressure. Next generation selective estrogen receptor modulators and degraders/downregulators (SERMs and SERDs) show clinical efficacy, but responses are often non-durable. A tyrosine to serine point mutation at position 537 in the ERα ligand binding domain (LBD) is among the most common and most pathogenic alteration in this setting. It enables endocrine therapy resistance by superceding intrinsic structural-energetic gatekeepers of ER hormone-dependence, it enhances metastatic burden by enabling neomorphic ER-dependent transcriptional programs, and it resists SERM and SERD inhibiton by reducing their binding affinities and abilities to antagonize transcriptional coregulator binding. However, a subset of SERMs and SERDs can achieve efficacy by adopting poses that force the mutation to engage in a new interaction that favors the therapeutic receptor antagonist conformation. We previously described a chemically unconventional SERM, T6I-29, that demonstrates significant anti-proliferative activities in Y537S ERα breast cancer cells. Here, we use a comprehensive suite of structural-biochemical, in vitro, and in vivo approaches to better T6I-29's activities in breast cancer cells harboring Y537S ERα. RNA sequencing in cells treated with T6I-29 reveals a neomorphic downregulation of DKK1, a secreted glycoprotein known to play oncogenic roles in other cancers. Importantly, we find that DKK1 is significantly enriched in ER+ breast cancer plasma compared to healthy controls. This study shows how new SERMs and SERDs can identify new therapeutic pathways in endocrine-resistant ER+ breast cancers.

Molecular Docking, Synthesis, Antiproliferative Activity against MCF-7, and In-vitro Alpha Amylase Activities of Newer Generation Pyrimidino Hydroxamic Acid Derivatives

A set of newer generation pyrimidine hydroxamic acid derivatives were designed, synthesized, and evaluated for antiproliferative activity against breast cancer cell line and in-vitro alpha-amylase activity. The design of the molecules was fully dependent upon the structural features of suberoyl anilide hydroxamic acid. Then all the designed molecules (S1-S100) were docked with 4LXZ HDAC2 enzyme and S1, S2, S16 showed good docking interaction scores as compared to SAHA. The interacting residues of (S1, S2, S16) and 4LXZ showed similar amino acid lining as present in the active site. The synthetic procedure of the molecules (S1, S2, S16) was divided into three parts such as synthesis of chalcone derivative using aromatic aldehyde and acetophenone, the reaction between chalcone and thiourea to form substituted pyrimidine-2-thiol, then finally substituted pyrimidine-2-thiol and 2-chloro-N-hydroxyacetamide reacted in the presence of dimethylformamide to obtain the best-docked molecules. All the molecules showed characteristic peaks in fourier-transform infrared (FTIR), proton nuclear magnetic resonance (1H-NMR) and mass spectrometry with sharp melting points and single peak in thin layer chromatography (TLC) plate. Finally antiproliferative activity against MCF-7 and in-vitro alpha amylase activity data confirmed that S1 was the best molecule among all the synthesized molecules.

Synthesis of 2-phenylnaphthalenoid amide derivatives and their topoisomerase IIα inhibitory and antiproliferative activities.

Topoisomerases are highly associated with cell proliferation, becoming an important target for the development of antitumor drugs. 2-Phenylnaphthalenoids (2PNs) have been identified as human DNA topoisomerase IIα (TopoIIα) inhibitors. In this study, based on the 2PN scaffold, 20 amide derivatives (J1-J10, K1-K10) were synthesized. Among them, K10 showed high TopoIIα inhibitory activity and stronger antiproliferation activity against HepG-2 and MDA-MB-231 cells (IC50 0.33 and 0.63 μM, respectively) than the positive control VP-16 (IC50 9.19 and 10.86 μM) and the lead F2 (IC50 0.64 and 1.51 μM). Meanwhile, K10 could also inhibit migration and promote apoptosis of HepG-2 and MDA-MB-231 cells. Therefore, K10 can be developed into a potent TopoIIα inhibitor as an antitumor agent. The structure-activity relationship was also discussed.

Synthesis and anti-proliferative effect of novel 4-Aryl-1, 3-Thiazole-TPP conjugates via mitochondrial uncoupling process

With the advent of mitochondrial targeting moiety such as triphenlyphosphonium cation (TPP+), targeting mitochondria in cancer cells has become a promising strategy for combating tumors. Herein, a series of novel 4-aryl-1,3-thiazole derivatives linked to TPP+ moiety were designed and synthesized. The cytotoxicity against a panel of four cancer cell lines was evaluated by CCK-8 assay. Most of these compounds exhibited moderate to good inhibitory activity over HeLa, PC-3 and HCT-15 cells while MCF-7 cells were less sensitive to most compounds. Among them, compound 12a exhibited a significant anti-proliferative activity against HeLa cells, and prompted for further investigation. Specifically, 12a decreased mitochondrial membrane potential and enhanced levels of reactive oxygen species (ROS). The flow cytometry analysis revealed that compound 12a could induce apoptosis and cell cycle arrest at G0/G1 phase in HeLa cells. In addition, mitochondrial bioenergetics assay revealed that 12a displayed mild mitochondrial uncoupling effect. Taken together, these findings suggest the therapeutic potential of compound 12a as an antitumor agent targeting mitochondria.

Green and chemical synthesized zinc oxide nanoparticles: Evaluation of their anti-proliferative activity against breast cancer cell line – An in vitro and in silico approach

Zinc Oxide nanoparticles (ZnO NPs) were synthesized through both chemical and green approaches using wheat grass (WG) extract. Characterization techniques included Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM) with Energy-Dispersive X-ray Spectroscopy (EDX), Fourier-transform infrared Spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), and Ultraviolet-visible (UV-Vis) spectroscopy. CS-ZnO NPs and WG-ZnO NPs exhibited characteristic surface plasmon resonance (SPR) peaks at 360 nm and 320 nm, respectively, with low polydispersity index (PDI) values indicating uniform nanoparticle dispersion. FTIR analysis revealed distinct functional groups on the ZnO NPs’ surface for stabilization. XPS confirmed atomic composition and oxidation state, while XRD confirmed their hexagonal wurtzite structure. SEM images revealed rod-shaped structures, supported by EDX analysis confirming ZnO NP formation through elemental content. The synthesized ZnO NPs demonstrated significant cytotoxicity against MDA-MB 231 breast cancer cells, causing changes in nuclear morphology, increased reactive oxygen species levels, and membrane damage. Wound healing assay highlighted their potential in inhibiting cancer metastasis. Molecular docking between WG compounds and breast cancer targets revealed that the enhanced efficacy of green-synthesized ZnO NPs could be attributed to covalent linkage of active molecules of WG onto the nanoparticle surface. Overall, ZnO NPs synthesized using the green method outperformed their chemically synthesized counterparts.

Adipokine Modulation in Endometrial Hyperplasia by Polyunsaturated Fatty Acids

Background Obesity is associated with a higher prevalence of endometrial hyperplasia, thereby increasing the risk of endometrial and ovarian cancers. The precise mechanisms linking obesity to endometrial hyperplasia remain unclear, but dysregulation of adipose tissue homeostasis is known to play a significant role. Hypertrophied adipocytes in obese individuals secrete various bioactive substances, including cytokines, growth factors, hormones, and metabolites. Additionally, hyperplastic adipocytes exhibit enhanced aromatase activity, leading to increased estrogen synthesis, which further promotes the development of endometrial hyperplasia. Purpose The purpose of this study is to explore the anti-inflammatory and anti-proliferative activities of the poly unsaturated fatty acids. Methodology An extensive literature survey has been performed to identify the role of adipokines and elevated endogenous estrogen levels in activating cell survival signaling pathways, such as PI3K/Akt/mTOR, MEK/ERK1, and JAK–STAT in endometrial cells and their possible role in Endometrial Hyperplasia. Further, the possible beneficial anti-inflammatory and anti-proliferative effects of polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) were explored. Results Numerous studies suggest the beneficial role of dietary fats, such as EPA, DHA, and AA in modulating the growth of endometrium in obesity-induced endometrial hyperplasia. PUFAs can activate adenosine monophosphate-activated protein kinase (AMPK), which inhibits gluconeogenesis and lipogenesis. It also phosphorylates acetyl-CoA, leading to a decrease in malonyl-CoA, which inhibits mitochondrial CPT1. Additionally, AMPK activation promotes β-oxidation, and PPAR-γ mechanisms by down regulating the NF-kB pathway involved in endometrial hyperplasia. Conclusion This review sheds light on the potential of PUFAs in mitigating estrogen synthesis, adipokine secretion, and endogenous aromatase activity in obesity induced endometrial hyperplasia. Furthermore, it critically evaluates the role and mechanisms of PUFAs in attenuating obesity-associated endometrial hyperplasia and reducing the risk of ovarian cancer.

Comprehensive analysis of phytochemical profiling, cytotoxic and antioxidant potentials, and identification of bioactive constituents in methanoic extracts of Sonneratia apetala fruit

In the delta region of Bangladesh, Sonneratia apetala, also known as Keora and mangrove apple, is widely recognized for its dual role as a source of both food and medicine. Seasonal S. apetala fruits were gathered from Hatiya, Noakhali, in October 2021. The samples were segregated into pericarps and seeds, then fractionated into methanol segments. The anti-proliferative activities of these samples against lung A549 cells were evaluated using the Trypan blue exclusion method. Additionally, High-Performance Liquid Chromatography (HPLC) was employed to quantify phenolic compounds, while standard protocols facilitated the identification of specific phytochemical constituents. Chemical profiling via Gas Chromatography-Mass Spectrometry (GC-MS) and the isolation and detection of bioactive compounds through column chromatography and Nuclear Magnetic Resonance (NMR) analysis were undertaken. The methanol fractions of the seeds and pericarp were found to contain carbohydrates, tannins, flavonoids, steroids, alkaloids, glycosides, and terpenoids, with the absence of saponins and anthraquinones. Notably, the anti-proliferative effect demonstrated statistical significance at a concentration of 300 μg/mL for both extracts. Furthermore, HPLC analysis identified and quantified six polyphenols: catechin hydrate, (−)-epicatechin, rutin hydrate, trans-ferulic acid, trans-cinnamic acid, myricetin, and kaempferol, with the following concentrations: 46.65 and 12.72; 349.29 and 140.39; 5.26 and 33.06; 10.35 and 29.28; ND and 11.93; and 10.03 and 7.90 mg/100 g in the methanol fraction of the seed and pericarp, respectively. GC-MS analysis of S. apetala fruit revealed five notable compounds with significant peak areas (%): 2-methyltetracosane, tetratetracontane, heptacosane, 1-chloro-2-hexyl-1-octanol, and phenol, 3,5-bis(1,1-dimethylethyl), exhibiting peak areas of 43.96, 35.8, and 15.95, respectively. Meanwhile, the notable peak in S. apetala seeds was 1,3-benzenedicarboxylic acid, bis(2-ethylhexyl) ester, with a peak area (%) of 100. These compounds are known for their anticancer and antioxidant properties. Therefore, S. apetala, particularly its seeds and fruits, shows promising potential for development into dietary supplements and functional foods.

Growth parameters, phytochemicals, and antitumor activity of wild and cultivated ice plants (Mesembryanthemum crystallinum L.)

AbstractThe ice plant (Mesembryanthemum crystallinum L.) is a halophyte that could become an alternative crop because of its interest as a functional food and its adaptation to high‐saline soils. In this work, leaves from wild ice plants were compared with their cultivated counterparts in a soilless system at different salinities and light exposures for assessing growth parameters, moisture, fatty acid profiles, total carotenoids, phenolic compounds, vitamin C, antioxidant activity, and antiproliferative activity against the HT‐29 colorectal cancer cell line. Moisture ranged between 876 and 955 g kg−1, and wild plants contained higher proportions of α‐linolenic acid (58.7%–60.7% of total fatty acids) than cultivated ones (20.4%–36.6%). Vitamin C ranged between 819 and 1143 mg kg−1 fresh leaves. Higher salinity led to a larger production of carotenoids, whereas plant mass, total phenolic content, and antioxidant activity increased in plants grown using L8 NS1 and L8 AP67 lamps in comparison with white‐light ones. Phenolic profiles were assessed by LC coupled to a hybrid mass spectrometer Q‐Orbitrap. Total phenolic acid content was 3–4‐fold higher than that of flavonoids, and sinapic, p‐coumaric, gallic, 4‐hydroxybenzoic, and 2‐hydroxy‐4‐methoxybenzoic acids, as well as gallocatechin, occurred in all samples. Hydroalcoholic extracts of ice plant leaves showed dose‐ and time‐dependent antiproliferative activity against the HT‐29 human colorectal cancer cell line, and GI50 was between 920 and 977 μg mL−1 of plant extract. This work contributes to improving knowledge about the growth parameters, phytochemical profiles, and biological activities of wild and cultivated ice plants.