Antiproliferative Properties Research Articles

Effect of Lupeol on the Expression of Neuro Inflammatory Signalling Molecules in Brain Tissues of High Fat Diet and Sucrose Fed Type-2 Diabetic Rats

Lupeol has anti- inflammatory, antimicrobial, anti-protozoal, anti-proliferative, anti-invasion, anti-angiogenic and cholesterol-lowering properties. However, the mechanisms underlying the effect of lupeol on neuroinflammatory signalling molecules have not yet been identified. The study was designed to study the effect of lupeol on the expression of inflammatory signalling molecules in brain tissue of high-fat diet and sucrose-fed type-2 diabetic rats. Adult male albino rats of Wistar 150–180 days old with 180–200 g body weight (b.wt) were divided into four groups of six rats each. Group I: Control (vehicle-treated): Group II: High fat diet-induced type-2 diabetic rats; Group III: Type-2 diabetic rats treated with lupeol (25 mg/kg b.wt/day) orally for 30 days and Group IV: Type-2 diabetic rats treated with metformin (50 mg/kg, b.wt/day orally for 30 days. After 30 days of treatment, the animals were anaesthetized, and brain tissue was dissected and used for the assessment of mRNA expression analysis. Type-2 diabetic animals showed a significant increase (p<0.05) in TNF-α and IL-6 mRNA levels in brain tissue in high-fat diet-induced type-2 diabetic animals. However, lupeol treatment, effectively reduced (p<0.05) the neuroinflammatory signaling molecules (TNF- α and IL-6 mRNA) showing that lupeol has significant role over the control of neuroinflammatory signaling. Our present findings clearly show that lupeol has a significant role in reducing neuroinflammation via the downregulation of TNF-α and IL-6 in brain tissues and hence, lupeol can be a potential natural drug for the treatment of diabetic neuropathy.

Dissecting the Puzzling Roles of FAM46C: A Multifaceted Pan-Cancer Tumour Suppressor with Increasing Clinical Relevance.

FAM46C is a well-established tumour suppressor with a role that is not completely defined or universally accepted. Although FAM46C expression is down-modulated in several tumours, significant mutations in the FAM46C gene are only found in multiple myeloma (MM). Consequently, its tumour suppressor activity has primarily been studied in the MM context. However, emerging evidence suggests that FAM46C is involved also in other cancer types, namely colorectal, prostate and gastric cancer and squamous cell and hepatocellular carcinoma, where FAM46C expression was found to be significantly reduced in tumoural versus non-tumoural tissues and where FAM46C was shown to possess anti-proliferative properties. Accordingly, FAM46C was recently proposed to function as a pan-cancer prognostic marker, bringing FAM46C under the spotlight and attracting growing interest from the scientific community in the pathways modulated by FAM46C and in its mechanistic activity. Here, we will provide the first comprehensive review regarding FAM46C by covering (1) the intracellular pathways regulated by FAM46C, namely the MAPK/ERK, PI3K/AKT, β-catenin and TGF-β/SMAD pathways; (2) the models regarding its mode of action, specifically the poly(A) polymerase, intracellular trafficking modulator and inhibitor of centriole duplication models, focusing on connections and interdependencies; (3) the regulation of FAM46C expression in different environments by interferons, IL-4, TLR engagement or transcriptional modulators; and, lastly, (4) how FAM46C expression levels associate with increased/decreased tumour cell sensitivity to anticancer agents, such as bortezomib, dexamethasone, lenalidomide, pomalidomide, doxorubicin, melphalan, SK1-I, docetaxel and norcantharidin.

Marine-derived antimicrobial peptide piscidin-1 triggers extrinsic and intrinsic apoptosis in oral squamous cell carcinoma through reactive oxygen species production and inhibits angiogenesis

Cancer of the head and neck encompasses a wide range of cancers, including oral and oropharyngeal cancers. Oral cancer is often diagnosed at advanced stages and has a dismal prognosis. Piscidin-1, a marine antimicrobial peptide (AMP) containing approximately 22 amino acids, also exhibits significant anticancer properties. We investigated the possible anti-oral cancer effects of piscidin-1 and clarified the mechanisms underlying these effects. We treated the oral squamous cell carcinoma cell lines OC2 and SCC4 with piscidin-1. Cell viability and the expression of different hallmark apoptotic molecules, including reactive oxygen species (ROS), were tested using the appropriate MTT assay, flow cytometry and western blotting assays, and human umbilical vein endothelial cell (HUVEC) wound healing, migration, and tube formation (angiogenesis) assays. Piscidin-1 increases cleaved caspase 3 levels to induce apoptosis. Piscidin-1 also increases ROS levels and intensifies oxidative stress in the endoplasmic reticulum and mitochondria, causing mitochondrial dysfunction. Additionally, it decreases the oxygen consumption rates and activity of mitochondrial complexes I–V. As expected, the antioxidants MitoTEMPOL and N-acetylcysteine reduce piscidin-1–induced ROS generation and intracellular calcium accumulation. Piscidin-1 also inhibits matrix metalloproteinase (MMP)-2/-9 expression in HUVECs, affecting migration and tube formation angiogenesis. We demonstrated that piscidin-1 can promote apoptosis via both intrinsic and extrinsic apoptotic pathways and findings indicate that piscidin-1 has anti-proliferative and anti-angiogenic properties in oral cancer treatment. Our study on piscidin-1 thus provides a basis for future translational anti-oral cancer drug research and a new theoretical approach for anti-oral cancer clinical research.

Triptolide, a Cancer Cell Proliferation Inhibitor, Causes Zebrafish Muscle Defects by Regulating Notch and STAT3 Signaling Pathways.

Triptolide is a natural compound in herbal remedies with anti-inflammatory and anti-proliferative properties. We studied its effects on critical signaling processes within the cell, including Notch1 and STAT3 signaling. Our research showed that triptolide reduces cancer cell proliferation by decreasing the expression of downstream targets of these signals. The levels of each signal-related protein and mRNA were analyzed using Western blot and qPCR methods. Interestingly, inhibiting one signal with a single inhibitor alone did not significantly reduce cancer cell proliferation. Instead, MTT assays showed that the simultaneous inhibition of Notch1 and STAT3 signaling reduced cell proliferation. The effect of triptolide was similar to a combination treatment with inhibitors for both signals. When we conducted a study on the impact of triptolide on zebrafish larvae, we found that it inhibited muscle development and interfered with muscle cell proliferation, as evidenced by differences in the staining of myosin heavy chain and F-actin proteins in confocal fluorescence microscopy. Additionally, we noticed that inhibiting a single type of signaling did not lead to any significant muscle defects. This implies that triptolide obstructs multiple signals simultaneously, including Notch1 and STAT3, during muscle development. Chemotherapy is commonly used to treat cancer, but it may cause muscle loss due to drug-related adverse reactions or other complex mechanisms. Our study suggests that anticancer agents like triptolide, inhibiting essential signaling pathways including Notch1 and STAT3 signaling, may cause muscle atrophy through anti-proliferative activity.

Structure-Activity Relationship Studies on Highly Functionalized Pyrazole Hydrazones and Amides as Antiproliferative and Antioxidant Agents.

Aminopyrazoles represent interesting structures in medicinal chemistry, and several derivatives showed biological activity in different therapeutic areas. Previously reported 5-aminopyrazolyl acylhydrazones and amides showed relevant antioxidant and anti-inflammatory activities. To further extend the structure-activity relationships in this class of derivatives, a novel series of pyrazolyl acylhydrazones and amides was designed and prepared through a divergent approach. The novel compounds shared the phenylamino pyrazole nucleus that was differently decorated at positions 1, 3, and 4. The antiproliferative, antiaggregating, and antioxidant properties of the obtained derivatives 10-22 were evaluated in in vitro assays. Derivative 11a showed relevant antitumor properties against selected tumor cell lines (namely, HeLa, MCF7, SKOV3, and SKMEL28) with micromolar IC50 values. In the platelet assay, selected pyrazoles showed higher antioxidant and ROS formation inhibition activity than the reference drugs acetylsalicylic acid and N-acetylcysteine. Furthermore, in vitro radical scavenging screening confirmed the good antioxidant properties of acylhydrazone molecules. Overall, the collected data allowed us to extend the structure-activity relationships of the previously reported compounds and confirmed the pharmaceutical attractiveness of this class of aminopyrazole derivatives.

Combined untargeted metabolomics and network pharmacology approaches to reveal the therapeutic role of withanolide B in psoriasis

Psoriasis is a refractory inflammatory skin disorder in which keratinocyte hyperproliferation is a crucial pathogenic factor. Up to now, it is commonly acknowledged that psoriasis has a tight connection with metabolic disorders. Withanolides from Datura metel L. (DML) have been proved to possess anti-inflammatory and anti-proliferative properties in multiple diseases including psoriasis. Withanolide B (WB) is one of the abundant molecular components in DML. However, existing experimental studies regarding the potential effects and mechanisms of WB on psoriasis still remain lacking. Present study aimed to integrate network pharmacology and untargeted metabolomics strategies to investigate the therapeutic effects and mechanisms of WB on metabolic disorders in psoriasis. In our study, we observed that WB might effectively improve the symptoms of psoriasis and alleviate the epidermal hyperplasia in imiquimod (IMQ)-induced psoriasis-like mice. Both network pharmacology and untargeted metabolomics results suggested that arachidonic acid metabolism and arginine and proline metabolism pathways were linked to the treatment of psoriasis with WB. Meanwhile, we also found that WB may affect the expression of regulated enzymes 5-lipoxygenase (5-LOX), 12-LOX, ornithine decarboxylase 1 (ODC1) and arginase 1 (ARG1) in the arachidonic acid metabolism and arginine and proline metabolism pathways. In summary, this paper showed the potential metabolic mechanisms of WB against psoriasis and suggested that WB would have greater potential in psoriasis treatment.

New treatment alternatives for primary and metastatic colorectal cancer by an integrated transcriptome and network analyses

Metastatic colorectal cancer (CRC) is still in need of effective treatments. This study applies a holistic approach to propose new targets for treatment of primary and liver metastatic CRC and investigates their therapeutic potential in-vitro. An integrative analysis of primary and metastatic CRC samples was implemented for alternative target and treatment proposals. Integrated microarray samples were grouped based on a co-expression network analysis. Significant gene modules correlated with primary CRC and metastatic phenotypes were identified. Network clustering and pathway enrichments were applied to gene modules to prioritize potential targets, which were shortlisted by independent validation. Finally, drug-target interaction search led to three agents for primary and liver metastatic CRC phenotypes. Hesperadin and BAY-1217389 suppress colony formation over a 14-day period, with Hesperadin showing additional efficacy in reducing cell viability within 48 h. As both candidates target the G2/M phase proteins NEK2 or TTK, we confirmed their anti-proliferative properties by Ki-67 staining. Hesperadinin particular arrested the cell cycle at the G2/M phase. IL-29A treatment reduced migration and invasion capacities of TGF-β induced metastatic cell lines. In addition, this anti-metastatic treatment attenuated TGF-β dependent mesenchymal transition. Network analysis suggests IL-29A induces the JAK/STAT pathway in a preventive manner.

Supercritical CO2 Extraction of Fatty Acids, Phytosterols, and Volatiles from Myrtle (Myrtus communis L.) Fruit.

Myrtle (Myrtus communis L.) is a coastal Mediterranean aromatic medicinal plant rich in essential oil components, flavonoids, and phenolic acids. Studies highlight the potential health benefits of myrtle bioactive compounds with antioxidant and antiproliferative properties. Since limited research exists on myrtle fruit's lipid fraction, the aim of this study was to apply supercritical CO2 extraction to obtain bioactive compounds from myrtle berries focusing on the fatty acids, sterols, and essential oils. The optimization of the supercritical CO2 extraction of myrtle fruit using CO2 as solvent was carried out using the response surface methodology with Box-Behnken experimental design. The following conditions were tested: temperature (40, 50, and 60 °C), pressure (200, 300, and 400 bar), and flow rate (20, 30, and 40 g min-1) on the yield of lipid extract as well as on the yield of fatty acids, phytosterols, and volatiles present in the extract and constituting its bioactive potential. In the extracts examined, 36 fatty acids, 7 phytosterols, and 13 volatiles were identified. The average yield of the extract was 5.20%, the most abundant identified fatty acid was essential cis-linolenic acid (76.83%), almost 90% of the total phytosterols were β-sitosterol (12,465 mg kg-1), while myrtenyl acetate (4297 mg kg-1) was the most represented volatile compound. The optimal process conditions obtained allow the formulation of extracts with specific compositions.

Anthriscus sylvestris-Noxious Weed or Sustainable Source of Bioactive Lignans?

Anthriscus sylvestris (L.) Hoffm. (Apiaceae), commonly known as wild chervil, has gained scientific interest owing to its diverse phytochemical profile and potential therapeutic applications. The plant, despite being categorized as a noxious weed, is traditionally used in treating various conditions like headaches, dressing wounds, and as a tonic, antitussive, antipyretic, analgesic, and diuretic. Its pharmacological importance stems from containing diverse bioactive lignans, especially aryltetralins and dibenzylbutyrolactones. One of the main compounds of A. sylvestris, deoxypodophyllotoxin, among its wide-ranging effects, including antitumor, antiproliferative, antiplatelet aggregation, antiviral, anti-inflammatory, and insecticidal properties, serves as a pivotal precursor to epipodophyllotoxin, crucial in the semisynthesis of cytostatic agents like etoposide and teniposide. The main starting compound for these anticancer medicines was podophyllotoxin, intensively isolated from Sinopodophyllum hexandrum, now listed as an endangered species due to overexploitation. Since new species are being investigated as potential sources, A. sylvestris emerges as a highly promising candidate owing to its abundant lignan content. This review summarizes the current knowledge on A. sylvestris, investigating its biological and morphological characteristics, and pharmacological properties. Emphasizing the biological activities and structure-activity relationship, this review underscores its therapeutic potential, thus encouraging further exploration and utilization of this valuable plant resource.

The Gut Connection: Exploring the Possibility of Implementing Gut Microbial Metabolites in Lymphoma Treatment.

Recent research has implicated the gut microbiota in the development of lymphoma. Dysbiosis of the gut microbial community can disrupt the production of gut microbial metabolites, thereby impacting host physiology and potentially contributing to lymphoma. Dysbiosis-driven release of gut microbial metabolites such as lipopolysaccharides can promote chronic inflammation, potentially elevating the risk of lymphoma. In contrast, gut microbial metabolites, such as short-chain fatty acids, have shown promise in preclinical studies by promoting regulatory T-cell function, suppressing inflammation, and potentially preventing lymphoma. Another metabolite, urolithin A, exhibited immunomodulatory and antiproliferative properties against lymphoma cell lines in vitro. While research on the role of gut microbial metabolites in lymphoma is limited, this article emphasizes the need to comprehend their significance, including therapeutic applications, molecular mechanisms of action, and interactions with standard chemotherapies. The article also suggests promising directions for future research in this emerging field of connection between lymphoma and gut microbiome.

Cannabidiol Inhibits Epithelial Ovarian Cancer: Role of Gut Microbiome.

Epithelial ovarian cancer is among the deadliest gynecological tumors worldwide. Clinical treatment usually consists of surgery and adjuvant chemo- and radiotherapies. Due to the high rate of recurrence and rapid development of drug resistance, the current focus of research is on finding effective natural products with minimal toxic side effects for treating epithelial ovarian tumors. Cannabidiol is among the most abundant cannabinoids and has a non-psychoactive effect compared to tetrahydrocannabinol, which is a key advantage for clinical application. Studies have shown that cannabidiol has antiproliferative, pro-apoptotic, cytotoxic, antiangiogenic, anti-inflammatory, and immunomodulatory properties. However, its therapeutic value for epithelial ovarian tumors remains unclear. This study aims to investigate the effects of cannabidiol on epithelial ovarian tumors and to elucidate the underlying mechanisms. The results showed that cannabidiol has a significant inhibitory effect on epithelial ovarian tumors. In vivo experiments demonstrated that cannabidiol could inhibit tumor growth by modulating the intestinal microbiome and increasing the abundance of beneficial bacteria. Western blot assays showed that cannabidiol bound to EGFR/AKT/MMPs proteins and suppressed EGFR/AKT/MMPs expression in a dose-dependent manner. Network pharmacology and molecular docking results suggested that cannabidiol could affect the EGFR/AKT/MMPs signaling pathway.

Compound 225# inhibits the proliferation of human colorectal cancer cells by promoting cell cycle arrest and apoptosis induction.

Colorectal cancer (CRC) ranks as the second leading cause of cancer‑related death worldwide due to its aggressive nature. After surgical resection, >50% of patients with CRC require adjuvant therapy. As a result, eradicating cancer cells with medications is a promising method to treat patients with CRC. In the present study, a novel compound was synthesized, which was termed compound 225#. The inhibitory activity of compound 225# against CRC was determined by MTT assay, EdU fluorescence labeling and colony formation assay; the effects of compound 225# on the cell cycle progression and apoptosis of CRC cells were detected by flow cytometry and western blotting; and the changes in autophagic flux after the administration of compound 225# were detected using the double fluorescence fusion protein mCherry‑GFP‑LC3B and western blotting. The results demonstrated that compound 225# exhibited antiproliferative properties, inhibiting the proliferation and expansion of CRC cell lines in a time‑ and dose‑dependent manner. Furthermore, compound 225# triggered G2/M cell cycle arrest by influencing the expression of cell cycle regulators, such as CDK1, cyclin A1 and cyclin B1, which is also closely related to the activation of DNA damage pathways. The cleavage of PARP and increased protein expression levels of PUMA suggested that apoptosis was triggered after treatment with compound 225#. Moreover, the increase in LC3‑II expression and stimulation of autophagic flux indicated the activation of an autophagy pathway. Notably, compound 225# induced autophagy, which was associated with endoplasmic reticulum (ER) stress. In accordance with the in vitro findings, the in vivo results demonstrated that compound 225# effectively inhibited the growth of HCT116 tumors in mice without causing any changes in their body weight. Collectively, the present results demonstrated that compound 225# not only inhibited proliferation and promoted G2/M‑phase cell cycle arrest and apoptosis, but also initiated cytoprotective autophagy in CRC cells by activating ER stress pathways. Taken together, these findings provide an experimental basis for the evaluation of compound 225# as a novel potential medication for CRC treatment.

Design and Synthesis of Aspirin-chalcone Mimic Conjugates as Potential Anticancer Agents.

Extensive research has been conducted on aspirin, a widely recognized NSAID medication, regarding its potential as an anticancer agent. Studies have revealed its ability to trigger cell death in different types of cancer cells. A set of aspirin-chalcone mimic conjugates 5a-k and 6a-d utilizing the freshly prepared acid chloride of aspirin moiety has been designed and synthesized. To evaluate the newly developed compounds, the NCI 60- cell line panel was employed to assess their anti-proliferative properties. Subsequently, cell cycle analysis was conducted along with an examination of the compounds' impact on the levels of p53, Bax, Bcl-2, active caspase- 3, and their inhibition mechanism of tubulin polymerization. Derivative 6c displayed the best anticancer activity among the tested series while 6d was the best against breast cancer MDA-MB-468, therefore both of them were selected for the 5-dose stage, however, targeting MDA-MB-468, PI-flow cytometry of compound 6d proved the triggered cell growth arrest at the G1/S phase avoiding the mitotic cycle in MDA-MB-468 cells. Similarly, the upregulation of oncogenic parameters such as caspase-3, p53, and Bax/Bcl-2, along with the inhibition of PARP-1 enzyme level, was observed with compound 6d. This compound also exhibited a significant ability to induce apoptosis and disrupt the intracellular microtubule network through a promising activity as a tubulin polymerization inhibitor with IC50 = 1.065 ± 0.024 ng/ml. Furthermore, to examine the manner in which compound 6d binds to the active pocket of the tubulin polymerization enzyme, a molecular docking study was conducted. The study indicated that compound 6d could be a powerful microtubule-destabilizing agent. Therefore, further research on 6d could be worthwhile.

In Vitro Antiviral and Anticancer Effects of Tanacetum sinaicum Essential Oil on Human Cervical and Breast Cancer.

Cervical cancer has been linked to human papillomavirus (HPV) types 16 and 18. Essential oils (EOs) are vital natural products of plants with various therapeutic and biological properties. The purpose of this study is to investigate and assess Tanacetum sinaicum essential oil's possible antiviral and anticancer properties, with a focus on its in vitro effects on human cervical cancer and human breast adenocarcinoma cell lines. Tanacetum sinaicum EO was extracted via hydrodistillation (HD) and characterized using gas chromatography-mass spectrometry (GC-MS). MTT assay was used to determine the cell viability of Hela (a human epithelial cervical cancer) and MCF-7 (human breast adenocarcinoma) cell lines. Quantitative real-time polymerase chain reaction (PCR) was utilized to assess the antiviral efficacy of EO against HPV-16 and 18, and anti-metastatic characteristics. The biological activity of EO was assessed using Autophage and Cell genotoxicity via the comet assay. EO is mostly composed of chrysanthenyl acetate, thujone, and verbenol. The cell viability was reduced after 24 hours of incubation at doses from 100 to 400 µg/ml. Concentrations of 800 to 3,200 µg/ml significantly inhibit cell growth. After a 24-hour incubation period, doses ranging from 100 to 400 µg/ml reduced cell viability from 62 to 72%. Concentrations of 800 to 3,200 µg/ml significantly suppress cell growth by over 95%. In MCF7 and HeLa cell lines, EO lowered virus copy numbers in a dose-dependent manner, with higher concentrations of the oil inhibiting virus replication more effectively. EO treatment increased the number of autophagosomes/autolysosomes and acidic vesicular organelles in both cell lines. On the HeLa and MCF7 cell lines, EO demonstrated antiproliferative and antimetastatic effects. The results demonstrated that EO had dose-dependent genotoxic effects on both cancer cell lines, as evidenced by DNA damage. Tanacetum sinaicum EO is a prospective source of natural bioactive compounds that can be employed in pharmaceutical and medicinal applications due to its antiviral, antiproliferative, anti-metastatic and genotoxic properties.

Effect of 2-methoxyestradiol on mammary tumor initiation and progression.

The anti-cancer agent 2-methoxyestradiol (2-ME) has been shown to have anti-proliferative and anti-angiogenic properties. Previously, the effect of 2-ME on early- and late-stage breast cancer (BC) was investigated in vivo using a transgenic mouse model (FVB/N-Tg(MMTV-PyVT)) of spontaneous mammary carcinoma. Anti-tumor effects were observed in late-stage BC with no effect on early-stage BC. Given the contrasting results obtained from the different BC stages, we have now investigated the effect of 2-ME when administered before the appearance of palpable tumors. Each mouse received 100 mg/kg 2-ME on day 30 after birth, twice per week for 28 days, while control mice received vehicle only. Animals were terminated on day 59. Lung and mammary tissue were obtained for immunohistochemical analysis of CD163 and CD3 expression, and histological examination was performed to analyze tumor necrosis. Additionally, blood samples were collected to measure plasma cytokine levels. 2-ME increased tumor mass when compared to the untreated animals (p = .0139). The pro-tumorigenic activity of 2-ME was accompanied by lower CD3+ T-cell numbers in the tumor microenvironment (TME) and high levels of the pro-inflammatory cytokine interleukin (IL)-1β. Conversely, 2-ME-treatment resulted in fewer CD163+ cells detectable in the TME, increased levels of tumor necrosis, increased IL-10 plasma levels, and low IL-6 and IL-27 plasma levels. Taken together, these findings suggest that 2-ME promotes early-stage BC development.

Enhancing the Antiproliferative Activity of Perillyl Alcohol against Glioblastoma Cell Lines through Synergistic Formulation with Natural Oils.

Due to its volatility, photostability, and gastrointestinal toxicity, Perillyl Alcohol (POH), a monoterpenoid component of various plant species, is a chemotherapeutic drug with insufficient efficacy. Many naturally occurring bioactive compounds have well-known antiproliferative properties, including sefsol, jojoba, tea tree, and moringa oils. This study sought to develop an oil-based Self Nanoemulsifying Drug Delivery System (SNEDDS) using tween 80 as the surfactant and Dimethyl Sulfoxide (DMSO) or Polyethylene Glycol (PEG) 400 as the cosurfactant; the oils were used in a range of 10-20% to boost POH's anticancer efficacy. The formulations' size, charge, and impact on the viability of glioma cell lines, ANGM-CSS and A172, were evaluated. The developed SNEDDS formulations ranged from 3 nm to 362 nm in size, with electronegative surface charges between 5.05 and 17.0 mV and polydispersity indices between 0.3 and 1.0. The findings indicated that the antiproliferative effect of POH-loaded Nanoemulsion (NE) could be used as a possible anticancer therapy for glioblastoma in vitro, particularly when paired with the tested natural oils. Before asserting that this delivery technique is appropriate for glioblastoma therapy, additional in vitro and in vivo investigations are required.

Phytochemical composition of Lagenaria siceraria fruits from KwaZulu-Natal and Limpopo, South Africa

Lagenaria siceraria (Molina) Standley is a food and medicinal source with anti-proliferative, anti-fertility, anti-HIV and anti-cancerous properties. The current study investigated the phytochemical constituents of L. siceraria fruits using gas chromatography/mass spectrometry (GC–MS). Five isoprenoids present in all investigated landraces were 1-Dodecene, 2,3-Dimethyldodecane, E-15-Heptadecenal, Eicosane, and Tridecane, 6-propyl. Lighter metabolites such as 1-Dodecene and 2,3-Dimethyldodecane were recorded at a shorter retention time range of 9.08–16.29 min over a lower relative peak area ranging from 1.09 to 6.97%. However, heavier compounds (E-15-Heptadecenal, Eicosane and Tridecane, 6-propyl) had a longer retention time range of 13.42–18.00 mins over a higher relative peak area range of 2.25–11.41%. Cluster analysis grouped landraces into 5 clusters (I -V) according to their fruit and seed attributes, and isoprenoid units significant to each cluster. Terpenoids were the prominent phytochemicals present in fruits. This is the most comprehensive study on the fruit phytochemical constituents of different L. siceraria landraces to date.

Investigation (In-Vitro) of Antiproliferative Properties of Pseudopediastrum boryanum (Turpin) E. Hegewald Extracts in Various Cancer Cell Lines

In this study, antiproliferative effects of Pseudopediastrum boryanum isolated and cultured from Tokat Yeşilırmak River benthic habitats were investigated with in-vitro experiments. Anticancer activity tests of algae extracts were tested in cancer cell lines using the BrdU cell proliferation ELISA method. Vero (African Green Monkey Kidney Tumour Cells) and HeLa (Human Uterine Carcinoma Cells) were examined in concentrations of 100, 250 and 500 µg/ml. As a result of antiproliferative tests, P. boryanum was found to have effective anti-cancer properties. P. boryanum extract concentrations of 250 and 500 µg/ml had a significant cytotoxic effect on Vero and HeLa cell lines after 24 hours. According to the results, P. boryanum is estimated to be a good option for quantitative pharmaceutical analyses and could be evaluated in the pharmaceutical industry.

Hesperidin Enhanced the Antimigratory Activity and Senescence-Mediated G2/M Arrest Effect of PGV-1 Against T47D Luminal Breast Cancer Cells

Luminal breast cancer cells exhibit proliferative and metastatic characteristics. Exploration of the effective treatment with minimum side effects is necessary. This study aimed to confirm the combination treatment of a potent anticancer candidate PGV-1 and hesperidin on luminal breast cancer cells, T47D, covering its cytotoxic and anti-migratory activities. PGV-1 showed much stronger cytotoxicity with an IC50 value of 2 μM than that of hesperidin (200 μM) as evaluated by trypan blue exclusion assay, but the combination of the two compounds exhibited a synergistic effect. Propidium iodide (PI) staining with flow cytometry proved that the combination treatment increased the cell population in the G2/M phase. Additionally, the combination treatment increased senescent cells as shown in senescence associated β-galactosidase (SA-β-gal) assay which might correlate to its antiproliferative properties. In addition, the scratch wound healing assay showed that the combination also inhibited cell migration significantly. Molecular docking of the two compounds demonstrated potential interaction with their protein targets in cell cycle machinery, i.e. KIF1, CDK1, TOP2A, CA12, ESR1, FN1, and TYMS. Altogether, these findings strengthen the evidence of anti-cancer properties enhancement of PGV-1 in luminal breast cancer through combining the compound with hesperidin.

Nano-delivery Systems and Therapeutic Applications of Phytodrug Mangiferin.

In order to cure a range of ailments, scientists have investigated a number of bioactive antioxidant compounds produced from natural sources. Mangiferin, a C-glycosyl xanthone-structured yellow polyphenol, is abundant in mangoes and other dietary sources. In-depth examinations found that it is effective in the treatment of a variety of disorders due to its antiviral, anti-inflammatory, antiproliferative, antigenotoxic, antiatherogenic, radioprotective, nephroprotective, antihyperlipidemic, and antidiabetic properties. However, it is recognised that mangiferin's poor bioavailability, volatility, and limited solubility restrict its therapeutic usefulness. Over time, effective solutions to these problems have arisen in the shape of effective delivery methods. The current articles present a summary of the several researches that have updated Mangiferin's biopharmaceutical characteristics. Additionally, strategies for enhancing the bioavailability, stability, and solubility of this phytodrug have been discussed. This review provides detailed information on the development of innovative Mangiferin delivery methods such as nanoparticles, liposomes, micelles, niosomes, microspheres, metal nanoparticles, and complexation, as well as its therapeutic applications in a variety of sectors. This article provides effective guidance for researchers who desire to work on the formulation and development of an effective delivery method for improved magniferin therapeutic effectiveness.