Antiproliferative Effects Research Articles

Prenylated xanthones from mangosteen (Garcinia mangostana) target oxidative mitochondrial respiration in cancer cells

Mangosteen (Garcinia mangostana) is well-known for its nutritional value and health benefits. Breast cancer is the most common cancer and the leading cause of cancer-related mortality among females worldwide. Here we show that the prenylated xanthones, α-mangostin, γ-mangostin, 9-hydroxycalabaxanthone (9-HCX), and garcinone E from the mangosteen pericarp exhibit cytotoxicity against a panel of human cancer cell lines including lung adenocarcinoma (A549), cervical carcinoma (HeLa), prostatic carcinoma (DU 145), pancreatic carcinoma (MIA PaCa-2), hepatocellular carcinoma (Hep G2), bladder urothelial cancer (5637), as well as the triple-negative breast cancer cells MDA-MB-231. In line with its higher predicted bioactivity score compared to other prenylated xanthones, 9-HCX induced the strongest antiproliferative and proapoptotic effects in MDA-MB-231 breast cancer xenografts in vivo. In different in vitro models, we demonstrate that prenylated xanthones from G. mangostana target mitochondria in cancer cells by inhibition of the mitochondrial respiratory chain complex II (α-mangostin, γ-mangostin, and garcinone E) and complex III (9-HCX) as shown in isolated mitochondria. Accordingly, oxidative mitochondrial respiration (OXPHOS) was inhibited, mitochondrial proton leak increased, and adenosine triphosphate (ATP) synthesis decreased as analyzed by Seahorse assay in MDA-MB-231 cells. Hence, the prenylated xanthones increased mitochondrial superoxide levels, induced mitochondrial membrane permeabilization, and initiated caspase 3/7-mediated apoptosis in MDA-MB-231 triple-negative breast cancer cells. Thus, prenylated xanthones from Garcinia mangostana exhibit anticancer activity based on interference with the mitochondrial respiration.

Thioredoxin Interacting Protein Expressed in Osteoblasts Mediates the Anti-Proliferative Effects of High Glucose and Modulates the Expression of Osteocalcin.

Hyperglycemia is associated with impaired bone health in patients with diabetes mellitus. Although a direct detrimental effect of hyperglycemia on the bone has been previously reported, the specific molecular mediator(s) responsible for the inhibitory effect of high glucose levels on the bone remains unclear. We hypothesized that thioredoxin-interacting protein (Txnip), an essential mediator of oxidative stress, is such a mediator. We cultured MG-63 cells (immortalized human osteoblasts) with normal or high glucose concentrations and transfected them with scrambled or Txnip-specific small interfering RNA (siRNA). High glucose levels increased Txnip expression and reduced MG-63 cell proliferation. The high-glucose level mediated reduction in cell proliferation was prevented in Txnip siRNA-transfected cells. In addition, we demonstrated that silencing Txnip mRNA expression in osteoblasts reduced the expression of the osteocalcin gene. Our results suggest that high glucose levels or silencing of Txnip mRNA expression may induce apoptosis in osteoblasts. Our findings indicate that Txnip is an intracellular mediator of the anti-proliferative effects of extracellular high glucose levels on osteoblasts.

Polymethoxylated flavone variations and in vitro biological activities of locally cultivated Citrus varieties in China

Citrus peels are rich in polymethoxylated flavones (PMFs), which have beneficial health and pharmacological properties. In this study, the profiles, variations, and biological activities of PMFs in the peel extracts of 27 Citrus varieties (eight species) native to China were investigated. UPLC-QTOF-MS/MS analysis revealed that mandarin accumulated more diversity and higher detectable PMF contents. Wangcangzhoupigan (ZPG) possessed the highest antioxidant capacity. Gailiangcheng (GLC) and Bingtangcheng (BTC), sweet oranges showed excellent inhibitory effects against pancreatic lipase and α-glucosidase, respectively. Most citrus extracts effectively inhibited the production of ROS and pro-inflammatory cytokines, while increasing the accumulation of anti-inflammatory cytokines. In addition, Limeng (LM), Cupig-oushigan (GSG), and Yanxiwanlu (YXWL) showed anti-proliferative effects against DU145 and PC3 cancer cells. This study provides a comprehensive PMF profile and biological activities of various citrus species and will benefit future functional citrus breeding practices aimed at designing plants rich in total or specific PMFs for health benefits.

THE COMPARATIVE STUDY OF THE EFFECT OF LOW-INTENSITY BROADBAND AND LOW-INTENSITY PULSED ULTRASOUND ON B16 MELANOMA CELLS IN VITRO

Aim. To evaluate the effect of low-intensity broadband ultrasound (UMUS) and low-intensity pulsed ultrasound (LIPUS) on B16 melanoma cells in vitro. Methods. The research was conducted on B16 melanoma cells under two modes of low-intensity ultrasonic sounding of cells, for which an SDG 2082 X Siglent generator (USA) with an ultrasonic emitter diameter of 20 mm was used; with a frequency for UMUS of 1-7 MHz, intensity of 30 mW/cm, pulse duration of 50 μs, and for LIPUS with a frequency of 1.5 MHz, intensity of 30 mW/cm, pulse duration of 200 μs. Both modes of cell sounding were carried out with threefold irradiation, once a day after which the distribution of cells by cycle phases, the level of apoptosis and proliferative activity was determined by the method of ductal cytofluorimetry. Results. Under the influence of UMUS ultrasonic sounding, the inhibition of the proliferation of melanoma cells by 1.6 times (P<0.05), a 2-fold decrease in the content of aneuploid cells, compared to the control, was found, however, cytostatic and proapoptotic effects were not recorded. Under the influence of LIPUS sounding, an anti-proliferative effect, an increase in the content of dead and apoptotic cells and a decrease in the DI-index compared to the corresponding control were found. Conclusions. Under the action of low-intensity broadband ultrasound (UMUS) and low-intensity pulsed ultrasound (LIPUS), a cytotoxic/cytostatic and pro-apoptotic effect and a decrease in the content of the aneuploid cell population were revealed.

Targeting Skp2 degradation with troxerutin decreases neointima formation

The proliferative and migratory abilities of vascular smooth muscle cells (VSMCs) play a crucial role in neointima formation following vascular injury. Skp2 facilitates proliferation and migration in cells through cell cycle regulation, presenting an important therapeutic target for atherosclerosis, pulmonary hypertension, and vascular restenosis. This study aimed to identify a natural product capable of inhibiting neointima formation post vascular injury. Here, we demonstrate that troxerutin, a flavonoid, significantly reduced viability and downregulated Skp2 in VSMCs. Moreover, troxerutin exhibited anti-proliferative effects on VSMCs and mitigated neointima formation. These findings collectively elucidate the intrinsic mechanism of troxerutin in treating atherosclerosis, pulmonary hypertension, and vascular restenosis by targeting the E3-linked enzyme Skp2.

The pro-differentiating capability of a flavonoid-rich extract of Citrus bergamia juice prompts autophagic death in THP-1 cells

Acute myeloid leukemia (AML) is a hematologic neoplasm, characterized by a blockage of differentiation and an unconstrained proliferation of immature myeloid cells. Recently, the survival of leukemia patients has increased thanks to the use of differentiating agents, though these may cause serious side effects. Hence, the search for safer differentiating compounds is necessary. Our aim was to assess the pro-differentiating effects of a flavonoid-rich extract of bergamot juice (BJe) in human monocytic leukemia THP-1 cells, an in vitro AML model. For the first time, we showed that treatment with BJe induced differentiation of THP-1 cells, changes in cell morphology and increased expression of differentiation-associated surface antigens CD68, CD11b and CD14. Moreover, BJe enhanced protein levels of autophagy-associated markers, such as Beclin-1 and LC3, as well as induced the phosphorylation of the MAPKs JNK, ERK and p38, hence suggesting a potential mechanism underlying its antiproliferative effects. Indeed, parallel experiments highlighted that BJe was able to hamper THP-1 cell growth. In conclusion, our study suggests that BJe induces the differentiation of THP-1 cells and reduces their proliferation, highlighting its potential in differentiation therapy of AML.

3,3’4-trimethoxy-4’-rutinosylellagic acid and its acetylated derivative: Antioxidant activity and antiproliferative effects on breast cancer cells and molecular docking study

Cancers account for many deaths worldwide and natural compounds and their derivatives are interesting chemotherapeutic agents for cancer drug development. In this study, a natural compound 3,3’4-trimethoxy-4’-rutinosylellagic acid (TR2) and its acetylated derivative 3,3’4-trimethoxy-4’-hexaacetylrutinosylellagic acid (TR22) were evaluated for their antioxidant and anticancer effects against estrogen sensitive (MCF-7) and estrogen non-sensitive (MDA-MB 231) breast adenocarcinoma. In the β-Carotene-linoleic acid assay, DPPH• radical scavenging and CUPRAC assay, the compound TR2 had better activity than the standard α-Tocopherol, while in the ABTS•+ assay, it was more active than both standards α- α-Tocopherol and BHA. Both compounds had good antioxidant effects with TR2 being more active than TR22. Both compounds inhibited growth of breast carcinoma cells when compared to the untreated controls after 72 h. Compound TR22 significantly (p < 0.001) inhibited proliferation of both MCF-7 and MDA-MB 231 breast carcinoma cell lines suggesting that acetylation reaction improves inhibition of breast cancer cells growth. On the contrary, TR2 exhibited better inhibitory effect of clone formation than TR22 suggesting that acetylation reduces the activity in this assay. Both compounds inhibited migration of the cancer cells when compared to the untreated control cells and compound TR2 exhibited greater cellular anti-migration effect than TR22 at the same concentration and after the same period of incubation. Molecular docking studies supplemented the results and revealed that TR2 and TR22 had appreciable interactions with tyrosine kinase with negative binding energies suggesting that they are potent receptor tyrosine kinase inhibitors which can impede on cancer progression.

Tibetan tea extract exerts anti-tumor effects and potentiate paclitaxel-induced cytotoxicity and apoptosis in human hepatocellular carcinoma cells HepG2

Tibetan Tea (TT), traditionally esteemed by indigenous communities on the Qinghai-Tibet Plateau for over thirteen centuries, is a post-fermented tea recognized for its wide spectrum of biological functions. These include antioxidant capabilities, hypocholesterolemic effects, anti-hyperglycemic properties, and immune system enhancement. Nevertheless, additional medicinal potentials of TT, including its anticancer effects, remain to be unveiled in empirical studies. We aimed to evaluate the antiproliferative and chemotherapy-enhancing effects of TT extract on human hepatocellular carcinoma (HCC) cells, thereby initiating an inquiry into the potential molecular mechanisms involved. In this study, it was observed that TT extract suppressed the proliferation of HCC cells and triggered significant apoptosis. This apoptotic induction was facilitated through the activation of caspase-3, caspase-8, and caspase-9, along with decreased expression ratio of Bcl-2/Bax protein in HCC cells. Moreover, the combinational treatment of TT extract and Paclitaxel (Taxol) was found to enhance the anticancer effect. The expression level of P-glycoprotein (P-gp) encoded by the MDR1 (Multiple Drug Resistance) gene was remarkably decreased, revealing that TT extract might have the potential to be utilized as an adjuvant to promote HCC treatment. In conclusion, the Tibetan Tea extract exhibits cytotoxic, anticancer, and chemosensitization properties.

Sulindac exhibits anti-proliferative and anti-invasive effects in uterine serous carcinoma cells

PurposeUterine serous carcinoma (USC) is a highly aggressive and frequently recurring subtype of endometrial cancer with limited treatment options for advanced or recurrent stages. Sulindac, a classic non-steroidal anti-inflammatory drug, has demonstrated anti-tumor activity in several pre-clinical tumor models. This study aims to evaluate the effect of sulindac on cell proliferation and invasion in USC cells.MethodsHuman USC cell lines ARK-1 and SPEC2 were treated with different concentrations of sulindac. Cell proliferation was assessed using MTT and colony formation assays. ELISA assays measured cellular stress, cleaved caspase 3 activity, antioxidant ability, and adhesion. Cell cycle arrest was evaluated by Cellometer. The invasive capability was detected by wound healing assay. Western blotting was used to analyze the changes in protein expression induced by sulindac.ResultsExposure to sulindac decreased cellular viability in a dose-dependent manner in ARK-1 and SPEC2 cells. Sulindac effectively inhibited cell cycle progression, increased cellular stress, caused apoptosis, and reduced cell adhesion and invasion in USC cells. Additionally, sulindac decreased the expression of COX-2 and blocked phosphorylation of NF-κB induced by TNF-α.ConclusionSulindac is a potential therapeutic agent for USC that deserves further exploration in pre-clinical studies and potentially future clinical trials.

Evaluation of Pan-RAF Inhibitor LY3009120 on Human Uveal Melanoma Cell Line 92-1.

Uveal melanoma (UM) represents a prevailing primary intraocular malignancy, with a limited median overall survival among metastatic patients, and most tumors lack RAF/RAS mutations. The pan-RAF inhibitor LY3009120 has demonstrated valuable anti-tumor effects in a wide range of RAF/RASmut and wild-type (WT) tumor models. This study aimed to evaluate the antitumor effect of LY3009120 on 92-1 UM cell line. The effect of the pan-RAF inhibitor LY3009120 on cell proliferation, metabolic activity, biomass, early and late apoptosis/necrosis, and morphology was characterized in vitro (0.1-5 μM for 48 h/72 h). Furthermore, targeted panel sequencing was used to characterize the mutational landscape of the human 92-1 UM cell line. LY3009120 showed a significant concentration-dependent anti-proliferative effect on 92-1 cells. Cell proliferation and viability were significantly reduced at the lowest effective concentration of 0.5 μM (at 48 and 72 h, p<0.001). Furthermore, LY3009120 caused significant early apoptosis and late apoptosis/necrosis in 92-1 cells at 5 μM. Except for TP53, NGS showed that all 49 additional analysed genes (Oncomine myeloid panel) of 92-1 were wild-type, including BRAF, NRAS, and KRAS. The pan-RAF inhibitor LY3009120 demonstrated a significant anti-tumor effect on human UM cell line 92-1 independent of the molecular BRAF and RAS mutational status.

Fused in silico and bioactivity evaluation method for drug discovery: T001-10027877 was identified as an antiproliferative agent that targets EGFRT790M/C797S/L858R and EGFRT790M/L858R

BackgroundFacing the significant challenge of overcoming drug resistance in cancer treatment, particularly resistance caused by mutations in epidermal growth factor receptor (EGFR), the aim of our study was to identify potent EGFR inhibitors effective against the T790M/C797S/L858R mutant, a key player in resistance mechanisms.MethodsOur integrated in silico approach harnessed machine learning, virtual screening, and activity evaluation techniques to screen 5105 compounds from three libraries, aiming to find candidates capable of overcoming the resistance conferred by the T790M and C797S mutations within EGFR. This methodical process narrowed the search down to six promising compounds for further examination.ResultsKinase assays identified three compounds to which the T790M/C797S/L858R mutant exhibited increased sensitivity compared to the T790M/L858R mutant, highlighting the potential efficacy of these compounds against resistance mechanisms. Among them, T001-10027877 exhibited dual inhibitory effects, with IC50 values of 4.34 µM against EGFRT790M/C797S/L858R and 1.27 µM against EGFRT790M/L858R. Further investigations into the antiproliferative effects in H1975, A549, H460 and Ba/F3-EGFRL858/T790M/C797S cancer cells revealed that T001-10027877 was the most potent anticancer agent among the tested compounds. Additionally, the induction of H1975 cell apoptosis and cell cycle arrest by T001-10027877 were confirmed, elucidating its mechanism of action.ConclusionsThis study highlights the efficacy of combining computational techniques with bioactivity assessments in the quest for novel antiproliferative agents targeting complex EGFR mutations. In particular, T001-10027877 has great potential for overcoming EGFR-mediated resistance and merits further in vivo exploration. Our findings contribute valuable insights into the development of next-generation anticancer therapies, demonstrating the power of an integrated drug discovery approach.

Iturin A and Gramicidin A inhibit proliferation, trigger apoptosis, and regulate inflammation in breast cancer cells

Biosurfactants with antibiotic, antiviral, anti-tumor, and immunomodulatory properties appear to have potential in cancer treatment due to their lack of known toxicities compared with conventional chemotherapy. However, there are few studies on the use of biosurfactants for the treatment of breast cancer. In this study, to develop a new strategy for breast cancer treatment, we evaluated the anti-proliferative, anti-inflammatory, anti-tumor, and apoptotic effects of two different biosurfactants (Iturin A and Gramicidin A) from bacillus in both single and binary combination on two breast cancer cell lines (MDA-MB-231 and MCF-7, which is estrogen receptor-negative and positive, respectively). First, the anti-proliferative effects of Iturin A and Gramicidin A, both single and in combination, were explored by MTT assay. Then, the effects of Iturin A and Gramicidin A on inflammatory factors were evaluated using the ELISA method. Apoptosis was assessed using Annexin V-PE/7-AAD and Giemsa staining methods. RT-qPCR analysis was used to evaluate the expressions of several cytokines with anti-tumor and apoptotic properties and the apoptotic BAX and BCL2 genes. Biosurfactants showed anti-proliferative and anti-tumor properties by decreasing the viability of MDA-MB-231 and MCF-7 cells depending on concentration and time (p < 0.05-p<0.01). Biosurfactants induced apoptosis by stimulating apoptotic cell death (p < 0.05-p<0.001) and by increasing BAX and decreasing BCL2 gene expression levels (p < 0.05-p<0.001) in breast cancer cells. Biosurfactants also regulated the expressions of extracellular and intracellular cytokines (IL-2, IL-6, IL-12, IL12RB2, TGFβ, TNFα, VEGF) and chemokines (IL-8, CCL2, CXCL10) in breast cancer cells (p < 0.05-p<0.01). Both single and binary combination applications of Iturin A and Gramicidin A biosurfactants, may potentially treat breast cancer patients, and the in vitro results presented here warrant further in vivo studies.

Biological activities of Stryphnodendron adstringens bark decoction

Stryphnodendron adstringens, called ‘barbatimão’, is used in Brazilian folk medicine given its healing, astringent, anti-inflammatory, and antimicrobial properties. However, data on its safe use remain inconclusive due to controversy about the risk posed by its ethnopharmacological intake to human health. Thus, the present study aims to quantify the main classes of compounds found in S. adstringens bark powder and investigate the biological activity of ‘barbatimão’ bark decoction against pathogenic bacterial strains. We also investigated its toxic activity using the Artemia salina test and its cytogenotoxicity using the Allium cepa test. Phenols (24.5 ± 1.5 mg mL-1), tannins (15.08 ± 0.02 mg mL-1), and flavonoids (1.33 ± 0.02 mg mL-1) were quantified in the S. adstringens decoction. This decoction exhibited antibacterial activity against Gram-positive strains and toxicity against A. salina. It was not possible to observe the S. adstringens bark decoction genotoxicity in the A. cepa roots because the cell cycle stopped at the prophase, indicating the decoction’s anti-proliferation effect. S. adstringens is a plant with great herbal potential; therefore, other study models must be used to investigate its potential antibacterial and anti-proliferation applications

P53 Status Influences the Anti-proliferative Effect Induced by IFITM1 Inhibition in Estrogen Receptor-positive Breast Cancer Cells.

Interferon-induced trans-membrane protein 1 (IFITM1) is known to be involved in breast cancer progression. We aimed to investigate its role in estrogen receptor (ER)-positive breast cancer cells with wild-type p53 and tamoxifen-resistant breast cancer cells. The ER-positive breast cancer cell lines, MCF-7 with wild-type p53 and T47D with mutant p53, were used. We established an MCF-7-derived tamoxifen-resistant cell line (TamR) by long-term culture of MCF-7 cells with 4-hydroxytamoxifen. IFITM1 inhibition in MCF-7 cells significantly decreased cell growth and migration. MCF-7 cells with suppression of IFITM1 using siRNA or ruxolitinib showed reduced cell viability after tamoxifen treatment compared with that in the control MCF-7 cells. Unexpectedly, mRNA and protein levels of IFITM1 were decreased in TamR cells compared with those in MCF-7 cells. TamR cells with suppression of IFITM1 using siRNA or ruxolitinib showed no change in cell viability after treatment with tamoxifen. P53 knockdown using siRNA reduced the mRNA levels of IRF9 and increased mRNA and protein levels of SOCS3 in MCF-7 cells, suggesting that loss or mutation of p53 can affect the induction of IFITM1 via the JAK/STAT signaling pathway in breast cancer. Furthermore, MCF-7 cells with p53 knockdown using siRNA showed no decrease in cell viability after tamoxifen treatment or IFITM1 inhibition, indicating that p53 status may be important for cell death after tamoxifen treatment or IFITM1 inhibition. IFITM1 inhibition may enhance the sensitivity to tamoxifen based on p53-dependent enhancement of IFN signaling in wild-type p53, ER-positive breast cancer cells.

Prominence of curcumin in anticancer strategies and innovation in bioimaging

Curcumin (CUR), a natural polyphenol derived from the rhizomes of Curcuma longa (turmeric), has garnered significant attention in recent years for its multifaceted potential in anticancer therapy and bio-imaging applications. This review article comprehensively explores the diverse anticancer properties of CUR, encompassing its potent anti-inflammatory, antioxidant, and anti-proliferative effects, as well as its ability to induce apoptosis and inhibit angiogenesis, making it a promising candidate in the fight against cancer. In addition to its therapeutic potential, CUR's unique physicochemical properties have enabled its utility as a versatile imaging agent for various bio-imaging modalities, including fluorescence imaging, magnetic resonance imaging (MRI), and positron emission tomography (PET). We investigate the molecular mechanisms underlying CUR's bio-imaging capabilities and discuss its various applications in cancer diagnosis, monitoring treatment responses, and elucidating biological processes. This comprehensive review provides valuable insights into the dual role of CUR as an anticancer agent and a bio-imaging tool, elucidate its potential in the development of novel cancer therapies and diagnostic approaches. The amalgamation of CUR's bio-imaging and therapeutic properties suggests its future as a pivotal player in personalized medicine and precision oncology.

Neratinib plus dasatinib is highly synergistic in HER2-positive breast cancer in vitro and in vivo

BackgroundHER2-targeted therapies have revolutionised the treatment of HER2-positive breast cancer. However, de novo resistance or the emergence of acquired resistance is a persistent clinical problem. Here we report that neratinib, an irreversible pan-HER inhibitor, in combination with the multi-kinase inhibitor dasatinib, currently used to treat certain leukemias, has strong anti-proliferative effects against models of HER2-positive breast cancer that are innately resistant to trastuzumab or have acquired resistance to neratinib. MethodsNeratinib plus dasatinib was examined in a panel of 20 breast cancer cell lines, including HER2-positive, estrogen-receptor-positive, triple negative, and acquired HER2-targeted therapy resistant models. Drug effects on migration and apoptosis induction was evaluated and signaling alterations were determined by reverse phase protein array (RPPA). In vivo efficacy was examined using orthotopically-implanted HCC1954 cells. ResultsSynergy was observed in cell lines innately resistant to trastuzumab, models with acquired resistance to neratinib, and in triple negative breast cancer cell lines. Further investigation showed that neratinib plus dasatinib induced apoptosis and inhibited cell migration to a greater degree than either drug alone. RPPA revealed that the combination caused suppression of key survival signaling through EGFR, Akt, and MAPK inhibition. In vivo, neratinib plus dasatinib was well tolerated and had a prolonged anti-tumor effect against HCC1954 xenografts. ConclusionsThis study provides a strong pre-clinical rationale for the clinical investigation neratinib and dasatinib in HER2+ breast cancer.

Pseudolaric Acid B Inhibits FLT4-induced Proliferation and Migration in Non-small Cell Lung Cancer.

Non-Small Cell Lung Cancer (NSCLC) has attracted much attention on account of the high incidence and mortality of cancers. Vascular Endothelial Growth Factor Receptor 3 (VEGFR3/FLT4), which is a highly expressed receptor in NSCLC, greatly regulates cancer proliferation and migration. Pseudolaric Acid B (PAB) is a diterpenoid acid with antitumor activity isolated from Pseudolarix kaempferi. This study aimed to explore the inhibitory effect of PAB targeting FLT4 in NSCLC. Cell membrane chromatography was used to evaluate the affinity of PAB binding on FLT4. NCIH1299 cells were used in this study, and an MTT assay was performed to determine the anti-proliferation effect of PAB. Cell cycle analysis was conducted to study the cycle arrest of PAB. Wound healing and Transwell assays assessed the rate of cell migration. Western blot analysis evaluated the expression of related proteins. PAB showed strong affinity to FLT4 with a KD value of 3.01 × 10- 6 M. Targeting FLT4 by PAB inactivated downstream P38MAPK and PI3K/AKT pathways, which inhibited the proliferation of NCI-H1299 cells. Meanwhile, PAB promoted G2/M phase arrest by influencing CyclinB1 and CDK1 complex formation to inhibit NCI-H1299 cell growth, but the effect was attenuated by knocking down the FLT4. Besides, PAB regulated MMP9 secretion through the Wnt/β-catenin signaling pathway to inhibit NCI-H1299 cell migration. However, the ability of PAB to inhibit migration was significantly weakened by FLT4 knockdown in NCI-H1299 cells. PAB can inhibit the proliferation and migration of NSCLC cells through targeting FLT4 and is expected to be a promising FLT4 inhibitor for NSCLC treatment.

Genotoxic and antiproliferative effect of Alpinia zerumbet (Zingiberaceae) essential oil in Allium cepa biotest

The species Alpinia zerumbet popularly known as colony is quite abundant in northeastern Brazil and is widely used for medicinal purposes, due to its hypotensive and cardiovascular effect, without, however, due scientific evidence. Therefore, the objective of this study was to evaluate the genotoxic and antiproliferative effect of A. zerumbet essential oil, in test systems with Allium cepa. The chemical composition of the essential oil was determined by gas chromatography coupled with mass spectrometry (GC-MS). The antiproliferative and genotoxic effect was tested in seven treatments with three replications, and five concentrations of essential oil (0.01 to 1.0%) using onion bulbs. Two roots were analyzed from each bulb, with a count of 500 cells per slide/root, totaling 3,000 cells per treatment. The results showed that the main chemical constituents of the essential oil were 1.8 cineole (60.50%) and terpinen-4-ol (23.80%). In the assays with A. cepa, both the mitotic index (MI) and the cellular alteration percentages differed significantly in relation to the control, through the appearance of chromosomal and nuclear aberrations at the concentrations tested, revealing possible harmful effects to human health.

A Benzimidazole-Based N-Heterocyclic Carbene Derivative Exhibits Potent Antiproliferative and Apoptotic Effects against Colorectal Cancer.

Background and Objectives: Colorectal cancer (CRC) remains a major global health issue. Although chemotherapy is the first-line treatment, its effectiveness is limited due to drug resistance developed in CRC. To overcome resistance and improve the prognosis of CRC patients, investigating new therapeutic approaches is necessary. Materials and Methods: Using human colorectal adenocarcinoma (HT29) and metastatic CRC (SW620) cell lines, the potential anticancer properties of a newly synthesized compound 1-(Isobutyl)-3-(4-methylbenzyl) benzimidazolium chloride (IMBZC) were evaluated by performing MTT cytotoxicity, cell migration, and colony formation assays, as well as by monitoring apoptosis-related protein and gene expression using Western blot and reverse transcription-quantitative polymerase chain reaction technologies. Results: Tested at various concentrations, the half-maximal inhibitory concentrations (IC50) of IMBZC on HT29 and SW620 cell growth were determined to be 22.13 µM (6.97 μg/mL) and 15.53 µM (4.89 μg/mL), respectively. IMBZC did not alter the cell growth of normal HEK293 cell lines. In addition, IMBZC inhibited cell migration and significantly decreased colony formation, suggesting its promising role in suppressing cancer metastasis. Mechanistic analyses revealed that IMBZC treatment increased the expression of pro-apoptotic proteins p53 and Bax, while decreasing the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL, thus indicating the induction of apoptosis in IMBZC-treated CRC cells, compared to untreated cells. Additionally, the addition of IMBZC to conventional chemotherapeutic drugs (i.e., 5-fluorouracil, irinotecan, and oxaliplatin) resulted in an increase in the cytotoxic potential of the drugs. Conclusions: This study suggests that IMBZC has substantial anticancer effects against CRC cells through its ability to induce apoptosis, inhibit cancer cell migration and colony formation, and enhance the cytotoxic effects of conventional chemotherapeutic drugs. These findings indicate that IMBZC could be a promising chemotherapeutic drug for the treatment of CRC. Further research should be conducted using in vivo models to confirm the anti-CRC activities of IMBZC.

Antibacterial and Antiproliferative Effect of ZnO Nanoparticles Prepared Using Origanum marjorana Plant and Garcinia indica Fruit extracts

Antibacterial and Antiproliferative Effect of ZnO Nanoparticles Prepared Using Origanum marjorana Plant and Garcinia indica Fruit extracts