Human Tumor Cell Research Articles

Chemical composition and cytotoxic activity of the essential oil of Hinterubera imbricata species collected in Venezuelan Andes

Hinterhubera imbricata Cuatrec. et Aristeg belongs to Asteraceae family and it is one of the six endemic species that grows in Venezuela Andean. Present investigation aimed to determine the chemical composition of the essential oil of Hinterhubera imbricata and to evaluate the cytotoxic activity in human tumor cell lines from MCF-7 (breast carcinoma without over-expression of the HER2/cerb-2), PANC-1 (pancreatic adenocarcinoma ductal type) and SKBr3 (breast carcinoma, in which the HER2/cerb-2 gene is overexpressed). Results indicated that essential oil was mainly composed of monoterpenes being α-phellandrene, α-pinene, β-phellandrene and p-cymene as major components. Cytotoxic analysis revealed that this essential oil exhibited antitumor activity in all human tumor lines tested being more cytotoxic for the pancreatic cancer tumor line. To the best of our knowledge there are no published studies regarding either the genus Hinterhubera or the species Hinterhubera imbricata, thus, present investigation is considered as a contribution to the genus Hinterhubera study.

High-dimensional mapping of human CEACAM1 expression on immune cells and association with melanoma drug resistance

BackgroundHuman carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is an inhibitory cell surface protein that functions through homophilic and heterophilic ligand binding. Its expression on immune cells in human tumors is poorly understood.MethodsAn antibody that distinguishes human CEACAM1 from other highly related CEACAM family members was labeled with 159Tb and inserted into a panel of antibodies that included specificity for programmed cell death protein 1 (PD1) and PD-L1, which are targets of immunotherapy, to gain a data-driven immune cell atlas using cytometry by time-of-flight (CyTOF). A detailed inventory of CEACAM1, PD1, and PD-L1 expression on immune cells in metastatic lesions to lymph node or soft tissues and peripheral blood samples from patients with treatment-naive and -resistant melanoma as well as peripheral blood samples from healthy controls was performed.ResultsCEACAM1 is absent or at low levels on healthy circulating immune cells but is increased on immune cells in peripheral blood and tumors of melanoma patients. The majority of circulating PD1-positive NK cells, innate T cells, B cells, monocytic cells, dendritic cells, and CD4+ T cells in the peripheral circulation of treatment-resistant disease co-express CEACAM1 and are demonstrable as discrete populations. CEACAM1 is present on distinct types of cells that are unique to the tumor microenvironment and exhibit expression levels that are highest in treatment resistance; this includes tumor-infiltrating CD8+ T cells.ConclusionsTo the best of our knowledge, this work represents the first comprehensive atlas of CEACAM1 expression on immune cells in a human tumor and reveals an important correlation with treatment-resistant disease. These studies suggest that agents targeting CEACAM1 may represent appropriate partners for PD1-related pathway therapies.

Reciprocal Interactions of Human Monocytes and Cancer Cells in Co-Cultures In Vitro.

The tumor microenvironment (TME) includes immune and stromal cells and noncellular extracellular matrix (ECM) components. Tumor-associated macrophages (TAMs) are the most important immune cells in TME and are crucial for carcinomas' progression. The purpose was to analyze direct and indirect interactions in co-culture of tumor cells with monocytes/macrophages and, additionally, to indicate which interactions are more important for cancer development. Cytokines, reactive oxygen species, nitric oxide level, tumor cell cycle and changes in tumor cell morphology after human tumor cells (Hep-2 and RK33 cell lines) with human monocyte/macrophage (THP-1 cell line) interactions were tested. Morphology and cytoskeleton organization of tumor cells did not change after co-culture with macrophages. In co-culture of tumor cells with human monocyte, changes in the percentage of tumor cells in cell cycle phases was observed. No significant changes in reactive oxygen species (ROS) were found in the co-culture as compared to the tumor cell mono-culture. Monocytes produced about three times higher ROS than tumor cells. In co-cultures, a lower nitric oxide (NOx) level was found as compared to the sum of the production by both mono-cultures. Co-culture conditions limited the production of cytokines (IL-4, IL-10 and IL-13) as compared to the sum of their level in mono-cultures. In conclusion, macrophages influence tumor cell growth and functions. Mutual (direct and paracrine) interactions between tumor cells and macrophages changed cytokine production and tumor cell cycle profile. The data obtained may allow us to initially indicate which kind of interactions may have a greater impact on cancer development processes.

In vitro anticancer study of novel curcumin derivatives via targeting PI3K/Akt/p53 signaling pathway.

Four new series of curcumin derivatives bearing NO-donating moiety were synthesized via etherification, nucleophilic substitution, and Knoevenagel condensation etc. The cytotoxicity activity of curcumin derivatives against five human tumor cell lines (A549, Hela, HepG2, MCF-7 and HT-29) and two normal cell lines (LO-2 and HK-2) has been studied. The results showed that compound 6a could inhibit the proliferation of MCF-7 cells remarkably and exhibit low toxicity to normal cells. Also, the underlying mechanism in vitro of compound 6a on MCF-7 was investigated. It has been found that compound 6a induced G2/M arrest and apoptosis of MCF-7 in a dose-dependent manner. Compound 6a-induced the fluorescence changes of ROS in MCF-7 cells confirmed the occurrence of apoptosis. Western Blot suggested that compound 6a decreased the expression of PI3K, as well as increased the expression of p53, cleaved caspase-9 and cleaved caspase-3. Furthermore, molecular docking revealed that compound 6a could bind well at active site of PI3K (3zim) with total score 9.59. Together, compound 6a, a potential PI3K inhibitor, may inhibit the survival of MCF-7 cells via interfering with PI3K/Akt/p53 pathway.

The Synthesis and Pharmacokinetics of a Novel Liver-Targeting Cholic Acid-Conjugated Carboplatin in Rats

A novel cholic acid-conjugated carboplatin (CP-CA) is developed as a liver-targeting prodrug of carboplatin (CP) for liver cancer. Instead of using CP as a raw material, CP-CA was synthesized simultaneously. This paper is focused on the comparison of CP-CA and CP with respect to their pharmacokinetic (PK) and tissue distribution profiles in rats after their intravenous administration. Additionally, their uptake by human liver tumor cell Huh7 and normal human liver cell HL7702 are investigated. The inductively coupled plasma mass spectrometry (ICP-MS) method is applied for the determination of platinum in plasma, tissues, and cells. The PK results show that both the AUC0–t and AUC0–∞ data on Pt for CP-CA are significantly higher than those for CP (p < 0.01), indicating that the plasma exposure of CP-CA is significantly higher than that of CP. The CL1, Vd1, and Vd2 data on Pt for CP-CA are significantly lower than those for CP (p < 0.01), while the MRT0-t is significantly higher (p < 0.01), which is possibly related to a higher PPBR, and can strongly support the higher AUC0–t and AUC0–∞ of Pt for CP-CA compared to for CP. The tissue distribution results show that CP-CA is mainly distributed and accumulated in the liver after its intravenous administration to rats, revealing its liver-targeting profile. Compared to CP, CP-CA is more easily taken up by human liver cancer cells and normal human liver cells. The results suggest that CP-CA has a potential for further development as a new prodrug specific to liver cancer.

Isolation and Total Synthesis of PM170453, a New Cyclic Depsipeptide Isolated from Lyngbya sp.

In our continuing search for biologically active new chemical entities from marine organisms, we have isolated a new cyclic depsipeptide, PM170453 (1), from a cyanobacterium of the genus Lyngbya sp., collected in the Indo-Pacific Ocean. Structure elucidation of the isolated compound was determined by spectroscopic methods including MS, 1H, 13C and 2D-NMR. To solve the supply problem for 1 and progress pharmaceutical development, the total synthesis of 1 that involves a total of 20 chemical steps in a convergent process was carried out. Its in vitro cytotoxic activity against four human tumor cell lines, as well as the inhibition of the interaction between the programmed cell death protein 1 PD-1 and its ligand PD-L1 were also evaluated.

Synthesis, structure and biological properties of the zinc(II) complexes with 5-(4-chlorophenyl)-1H-tetrazole and oligopyridine derivatives

In this work, we present six new zinc(II) complexes with the general formulas [Zn2(oligopyridine)2L4] and [Zn(oligopyridine)2L2], where L– = 5-(4-chlorophenyl)-1H-tetrazolate anion, and oligopyridine = 1,10-phenanthroline or 2,2′-bipyridine derivatives (dmphen – 4,7-dimethyl-1,10-phenanthroline, phen – 1,10 phenanthroline, dmbipy – 2,2′-bi-4-picoline, bipy – 2,2′-bipyridine), which have been synthesized with high yield and characterized by IR spectroscopy, elemental, thermogravimetric, single crystal and powder X-ray analyses. A distorted square-pyramidal and octahedral geometry of zinc(II) ion have been demonstrated by single crystal X-ray diffraction analysis. The tetrazolate ligand exhibits two types of coordination: monodentate, and bidentate-bridging via the N(2), N(3) or N(1), N(2) atoms. The behavior of all complexes in solution has been investigated by UV–Vis and the 1H, 13C NMR spectroscopy, conductometry, and mass spectrometry. The antimicrobial study of the compounds has been carried out against E. coli, St. aureus, P. italicum, and C. steinii, and [Zn2(dmbipy)2L4] has been shown to possess significant protistocidal properties. According to the cytotoxicity study,all complexes don’t have cytotoxic properties in 1–100 µM concentration range against tumor human cell lines (larynx carcinoma Hep2, hepatocellular carcinoma HepG2 and breast adenocarcinoma MCF-7) with the exception of complex 5 which has displayed significant cytotoxic effect (LC50 = 19.8 ± 2.4 μM) against Hep2 cells. However, obtained compounds have a pronounced cytostatic effect on all tumor cell lines.

Synthesis, crystal structure and anticancer activity of 4‑chloro-2-methoxybenzoic acid transition metal complexes

Seven novel transition metal complexes were synthesized from a starting material of 4‑chloro-2-methoxybenzoic acid, I: [Cu(4-Cl-2-MOBA)2(Py)2(H2O)2]; II: [Cu(4-Cl-2-MOBA)2(Imz)2]; III: [Co(4-Cl-2-MOBA)2(H2O)3.5]; IV: [Ni(4-Cl-2-MOBA)2(H2O)6]; V: [Ni(4-Cl-2-MOBA)2(DMF)]; VI: [Ni(4-Cl-2-MOBA)2(3-NH2–5-hypy)2(H2O)2O3.67] and VII: [Zn2(4-Cl-2-MOBA)3(4,4′-bipy)(Py)(HAc)]n by a one-pot, solvothermal method. All complexes were characterized by elemental analysis (EA), Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV–Vis), electrospray ionization mass spectrometry (ESI-MS) and single-crystal X-ray diffraction analysis (XRD). Single crystal XRD analyses showed that central metal ion type, auxiliary ligands and solvents acted synergistically to determine structural diversity. Complexes I-VII had cytotoxic activity towards the human tumor cell lines, A549 and SMMC-7721. Complex I showed the most potent cytotoxicity with an IC50 value of 8.976 μM for lung cancer cells and 13.94 μM for liver cancer cells.

Tumor-targeted nano-assemblies for energy-blocking cocktail therapy in cancer

Starvation therapy aims to “starve” tumor cells by cutting off their nutritional supply. However, due to the complex and varied energy metabolism of tumors, targeting a single nutrient supply often fails to yield significant therapeutic benefits. This study proposes a tumor energy cocktail therapy that combines metformin, an oxidative phosphorylation inhibitor, with 2-deoxy-d-glucose (2-DG), a glycolysis inhibitor, to target tumor cells. To minimize the dosage of both drugs, we have developed a drug delivery strategy that prepared metformin as a nanoderivative, denoted as MA-dots. These MA-dots not only preserve the antitumor properties of metformin but also serve as a targeted delivery platform for 2-DG, ensuring its direct reach to the tumor site. Upon reaching the acidic tumor environment, the composite disintegrates, releasing 2-DG to inhibit glycolysis by targeting hexokinase 2 (HK2), the key enzyme in glycolysis, while MA-dots inhibit mitochondrial OXPHOS. This dual action significantly reduces ATP production in tumor cells, leading to apoptosis. In human lung tumor cells, the half-maximal inhibitory concentration (IC50) of 2-DG@MA-dots was significantly lower than that of either metformin or 2-DG alone, showing a nearly 100-fold and 30-fold reduction in IC50 values to 11.78 µg mL−1, from 1159 µg mL−1 and 351.20 µg mL−1, respectively. In studies with A549 tumor-bearing mice, the combination of low-dose 2-DG and metformin did not impede tumor growth, whereas 2-DG@MA-dots markedly decreased tumor volume, with the mean final tumor volume in the combination treatment group being approximately 89 times greater than that in the 2-DG@MA-dot group. Statement of significanceMetformin is a promising antitumor agent capable of modulating mitochondrial oxidative phosphorylation to inhibit cancer growth. However, its antitumor efficacy is limited when used alone due to compensatory energy mechanisms. Hence, we introduced glycolysis inhibitor 2-deoxy-d-glucose (2-DG) to inhibit an alternative tumor energy pathway. In our study, we developed a drug delivery strategy using metformin-derived nanomedicine (MA-dots) to load 2-DG. This approach enables the co-delivery of both drugs and their synergistic effect at the tumor site, disrupting both energy pathways and introducing an innovative “energy cocktail therapy”.

α-pyrone derivatives from the endophytic Fusarium sp. L33 isolated from Dioscorea opposita

Two new α-pyrone derivatives, fusaripyrones C and D (1 and 2), along with six known compounds, namely phomapyrone C (3), fusarilactone A (4), pleospyrone D (5), 5-hydroxy-7-(2′-hydroxypropyl)-2-methyl-chromone (6), phenylacetic acid (7), and p-hydroxyphenylacetic acid (8) were isolated from Fusarium sp. L33, an endophytic fungus isolated from the leaves of Dioscorea opposita. Their structures were elucidated by NMR spectra, HRESIMS, optical rotation experiments and single-crystal X-ray diffraction analysis. Compounds 2, 3, and 6 were evaluated for their cytotoxic activity against five selected human tumor cell lines.

Quantitative Analysis of Isopimpinellin from Ammi majus L. Fruits and Evaluation of Its Biological Effect on Selected Human Tumor Cells.

Ammi majus L. (Apiaceae) is a medicinal plant with a well-documented history in phytotherapy. The aim of the present work was to isolate isopimpinellin (5,8-methoxypsoralen; IsoP) from the fruit of this plant and evaluate its biological activity against selected tumor cell lines. The methanol extract obtained with the use of an accelerated solvent extraction (ASE) method was the most suitable for the quantitative analysis of coumarins in the A. majus fruit matrix. The coumarin content was estimated by RP-HPLC/DAD, and the amount of IsoP was found to be 404.14 mg/100 g dry wt., constituting 24.56% of the total coumarin fraction (1.65 g/100 g). This, along with the presence of xanthotoxin (368.04 mg/100 g, 22.36%) and bergapten (253.05 mg/100 g, 15.38%), confirmed A. majus fruits as an excellent source of these compounds. IsoP was isolated (99.8% purity) by combined liquid chromatography/centrifugal partition chromatography (LC/CPC) and tested for the first time on its antiproliferative activity against human colorectal adenocarcinoma (HT29, SW620), osteosarcoma (Saos-2, HOS), and multiple myeloma (RPMI8226, U266) cell lines. MTT assay results (96 h incubation) demonstrated a dose- and cell line-dependent decrease in cell proliferation/viability, with the strongest effect of IsoP against the Saos-2 cell line (IC50; 42.59 µM), medium effect against U266, HT-29, and RPMI8226 (IC50 = 84.14, 95.53, and 105.0 µM, respectively), and very weak activity against invasive HOS (IC50; 321.6 µM) and SW620 (IC50; 711.30 µM) cells, as well as normal human skin fibroblasts (HSFs), with IC50; 410.7 µM. The mechanistic study on the Saos-2 cell line showed that IsoP was able to reduce DNA synthesis and trigger apoptosis via caspase-3 activation. In general, IsoP was found to have more potency towards cancerous cells (except for HOS and SW620) than against healthy cells. The Selective Index (SI) was determined, underlining the higher selectivity of IsoP towards cancer cells compared to healthy cells (SI = 9.62 against Saos-2). All these results suggest that IsoP might be a promising molecule in the chemo-prevention and treatment of primary osteosarcoma.

In vitro antiproliferative effects of Vatairea macrocarpa (Benth.) Ducke lectin on human tumor cell lines and in vivo evaluation of its toxicity in Drosophila melanogaster

Tumor cells may develop alterations in glycosylation patterns during the initial phase of carcinogenesis. These alterations may be important therapeutic targets for lectins with antitumor action. This work aimed to evaluate the in vitro cytotoxicity of VML on tumor and non-tumor cells (concentration of 25 μg/mL and then microdiluted) and evaluate its in vivo toxicity at different concentrations (1.8, 3.5 and 7.0 μg/mL), using Drosophila melanogaster. Toxicity in D. melanogaster evaluated mortality rate, as well as oxidative stress markers (TBARS, iron levels, nitric oxide levels, protein and non-protein thiols). The cytotoxicity assay showed that VML had cytotoxic effect on leukemic lines HL-60 (IC50 = 3.5 μg/mL), KG1 (IC50 = 18.6 μg/mL) and K562 (102.0 μg/mL). In the toxicity assay, VML showed no reduction in survival at concentrations of 3.5 and 7.0 μg/mL and did not alter oxidative stress markers at any concentrations tested. Cytotoxicity of VML from HL-60, KG1 and K562 cells could arise from the interaction between the lectin and specific carbohydrates of tumor cells. In contrast, effective concentrations of VML against no-tumor cells human keratinocyte – HaCat and in the D. melanogaster model did not show toxicity, suggesting that VML is a promising molecule in vivo studies involving leukemic cells.

Intracellular Osteopontin Promotes the Release of TNFα by Mast Cells to Restrain Neuroendocrine Prostate Cancer.

Neuroendocrine prostate cancer (NEPC) is an aggressive form of prostate cancer that emerges as tumors become resistant to hormone therapies or, rarely, arises de novo in treatment-naïve patients. The urgent need for effective therapies against NEPC is hampered by the limited knowledge of the biology governing this lethal disease. Based on our prior observations in the transgenic adenocarcinoma of the mouse prostate (TRAMP) spontaneous prostate cancer model, in which the genetic depletion of either mast cells (MC) or the matricellular protein osteopontin (OPN) increases NEPC frequency, we tested the hypothesis that MCs can restrain NEPC through OPN production, using in vitro co-cultures between murine or human tumor cell lines and MCs, and in vivo experiments. We unveiled a role for the intracellular isoform of OPN, so far neglected compared with the secreted isoform. Mechanistically, we unraveled that the intracellular isoform of OPN promotes TNFα production in MCs via the TLR2/TLR4-MyD88 axis, specifically triggered by the encounter with NEPC cells. We found that MC-derived TNFα, in turn, hampered the growth of NEPC. We then identified the protein syndecan-1 (SDC1) as the NEPC-specific TLR2/TLR4 ligand that triggered this pathway. Interrogating published single-cell RNA-sequencing data, we validated this mechanism in a different mouse model. Translational relevance of the results was provided by in silico analyses of available human NEPC datasets and by immunofluorescence on patient-derived adenocarcinoma and NEPC lesions. Overall, our results show that MCs actively inhibit NEPC, paving the way for innovative MC-based therapies for this fatal tumor. We also highlight SDC1 as a potential biomarker for incipient NEPC.

Discovery of Kebanmycins with Antibacterial and Cytotoxic Activities from the Mangrove-Derived Streptomyces sp. SCSIO 40068.

Mangrove derived actinomycetes are a rich reservoir of bioactive natural products and play important roles in pharmaceutical chemistry. In a screen of actinomycetes from mangrove rhizosphere sedimental environments, the isolated strain Streptomyces sp. SCSIO 40068 displayed strong antibacterial activity. Further fractionation of the extract yielded four new compounds kebanmycins A-D (1-4) and two known analogues FD-594 (5) and the aglycon (6). The structures of 1-6 were determined based on extensive spectroscopic data and single-crystal X-ray diffraction analysis. 1-3 featured a fused pyranonaphthaxanthene as an integral part of a 6/6/6/6/6/6 polycyclic motif, and showed bioactivity against a series of Gram-positive bacteria and cytotoxicity to several human tumor cells. In addition, the kebanmycins biosynthetic gene cluster (keb) was identified in Streptomyces sp. SCSIO 40068, and KebMT2 was biochemically characterized as a tailoring sugar-O-methyltransferase, leading to a proposed biosynthetic route to 1-6. This study paves the way to further investigate 1 as a potential lead compound.

HTS384 NCI60: The Next Phase of the NCI60 Screen.

The NCI60 human tumor cell line screen has been in operation as a service to the cancer research community for more than 30 years. The screen operated with 96-well plates, a 2-day exposure period to test agents, and following cell fixation, a visible absorbance endpoint by the protein-staining dye sulforhodamine B. In this study, we describe the next phase of this important cancer research tool, the HTS384 NCI60 screen. Although the cell lines remain the same, the updated screen is performed with 384-well plates, a 3-day exposure period to test agents, and a luminescent endpoint to measure cell viability based upon cellular ATP content. In this study, a library of 1,003 FDA-approved and investigational small-molecule anticancer agents was screened by the two NCI60 assays. The datasets were compared with a focus on targeted agents with at least six representatives in the library. For many agents, including inhibitors of EGFR, BRAF, MEK, ERK, and PI3K, the patterns of GI50 values were very similar between the screens with strong correlations between those patterns within the dataset from each screen. However, for some groups of targeted agents, including mTOR, BET bromodomain, and NAMPRTase inhibitors, there were limited or no correlations between the two datasets, although the patterns of GI50 values and correlations between those patterns within each dataset were apparent. Beginning in January 2024, the HTS384 NCI60 screen became the free screening service of the NCI to facilitate drug discovery by the cancer research community. Significance: The new NCI60 cell line screen HTS384 shows robust patterns of response to oncology agents and substantial overlap with the classic screen, providing an updated tool for studying therapeutic agents. See related commentary by Colombo and Corsello, p. 2397.

DBP Exposure Affects Oocyte Fertilization Via Extracellular Vesicles-Derived miR-116-5p in Ovarian Granulosa Cells Through Downregulating FOXO3a Expression.

Mono-butyl phthalate (MBP), the metabolite of dibutyl phthalate (DBP), is the most abundant phthalate metabolite found in Chinese women. Extracellular vesicles (EVs) are nanoscale lipid bilayer particles produced by extensive kinds of cells, serving a key role in intercellular communication. Extracellular vesicle miRNAs (EV-miRNAs) in follicular fluid (FF) have been evidenced to be associated with female reproductive health. The objective of this study was to investigate the associations of EV-miRNAs expressed profile with DBP exposure in FF of female participants and expose its potential mechanism in impaired oocyte development. Based on participants' FF MBP concentrations and fertilization status, we compared the miRNA expression between the FF-EVs of group A (high DBP exposure and impaired fertilization) and group B (low DBP exposure and normal fertilization). Compared with group B, miR-1246, miR-3679-5p, miR-423-5p, miR-5585-3p, miR-116-5p, miR-172-5p were upregulated, while miR-34b-3p was downregulated in group A. Target genes of the differently expressed miRNAs were predicted, and the functional analysis was performed. Furthermore, we exposed human ovarian granulosa tumor cell line (KGN) to MBP (4ug/L) to isolate the EVs from the culture medium and validated the expression levels of different miRNAs. We found that MBP exposure was significantly associated with increased levels of miR-116-5p (P = 0.01). In addition, we demonstrated that the most different miRNA, miR-116-5p regulated oocyte fertilization by inhibiting FOXO3a. Our findings suggested that EV-miRNAs in the FF might mediate MBP toxicity in oocytes.

Cordialin A isolated from Varronia curassavica Jacq. loaded in nanoemulsion as potential cytotoxic agent on human cervical tumor cells

Cordialin A isolated from Varronia curassavica Jacq. loaded in nanoemulsion as potential cytotoxic agent on human cervical tumor cells

Bioactives of the essential oil from the leaves of Eugenia pyriformis Cambess (Myrtaceae) on the effects of tobacco.

Lung cancer is the most commonly diagnosed and the main cause of cancer death, usually related to cigarette smoking. Furthermore, the microbiota of people exposed to cigarette smoke can be modified, making it difficult to eliminate opportunistic microorganisms. The leaves of Eugenia pyriformis are a by-product of fruit production and, to date, there have been no studies addressing the antiproliferative, anti-inflammatory, and antimicrobial activities. Investigate the antimicrobial, Nitric Oxide (NO)-production inhibition, and antiproliferative activities of the essential oil from E. pyriformis leaves and its possible effect on the treatment and prevention of damage caused by tobacco. The essential oil (EO) was obtained by hydrodistillation (3h). Its chemical composition was investigated by GC-MS. It was proposed to investigate antiproliferative activity against human tumor cell lines, namely, breast adenocarcinoma (MCF-7), lung (NCI-H460), cervical (HeLa), and hepatocellular (HepG2) carcinomas. A non-tumor primary culture from pig liver (PLP2) was also tested. The EO capacity to inhibit nitric oxide (NO) production was evaluated by a lipopolysaccharide stimulated murine macrophage cell line. Antibacterial and antifungal activities against opportunistic pathogens were investigated against seven strains of bacteria and eight fungi. The results indicated the presence of 23 compounds in the essential oil, the majority were spathulenol (45.63%) and β-caryophyllene oxide (12.72%). Leaf EO provided 50% inhibition of nitric oxide production at a concentration of 92.04µgmL-1. The EO also demonstrated antiproliferative activity against all human tumor cell lines studied, with GI50 values comprised between 270.86 and 337.25µgmL-1. The essential oil showed antimicrobial potential against the bacteria Listeria monocytogenes (Murray et al.) Pirie (NCTC 7973) and Salmonella Typhimurium ATCC 13311 (MIC 1870µgmL-1) and fungi Aspergillus versicolor ATCC 11730, Aspergillus ochraceus ATCC 12066, Penicillium ochrochloron ATCC 90288, Penicillium verrucosum var. cyclopium (Westling) Samson, Stolk & Hadlok (food isolate) (MIC 1870µgmL-1) and Trichoderma viride Pers. IAM 5061 (1,400µg mL-1). The demonstrated anti-inflammatory, antiproliferative, and antimicrobial activities in the leaves of E. pyriformis can add value to the production chain of this plant, being a possible option for preventing and combating cancer, including lung cancer.

Cladanthus scariosus Essential Oil and Its Principal Constituents with Cytotoxic Effects on Human Tumor Cell Lines.

Cladanthus is a small genus of the Asteraceae family comprising just five species that, apart from Cladanthus mixtus (L.) Chevall., has a large distribution in all the Mediterranean countries, mainly in the North Africa area. Several ethnopharmacological uses have been reported for species of this genus. Notably, Cladanthus scariosus (Ball) Oberpr. & Vogt is endemic to Morocco. Seeking to delve deeper into the phytochemistry and pharmacological aspects of this species, in this work, we investigated the essential oil (EO) obtained from the aerial parts of a locally sourced accession, hitherto unexplored, growing wild near Tizi n'Ticha, Morocco. The chemical composition of the EO, obtained by the hydrodistillation method, was evaluated by GC and GC-MS. The most abundant EO constituent was germacrene D (13.2%), the principal representative of the sesquiterpene hydrocarbons class (27.2%). However, the major class of constituents was monoterpene hydrocarbons (43.0%), with α-pinene (11.9%), sabinene (10.2%), p-cymene (8.5%), and α-phellandrene (5.2%) as the most abundant. The EO and its main constituents have been tested for their possible cytotoxic activity against three human tumor cell lines (MDA-MB 231, A375, and CaCo2) using the MTT assay, with corresponding IC50 values of 13.69, 13.21, and 22.71 µg/mL, respectively. Germacrene D and terpinen-4-ol were found to be the most active constituents with IC50 values between 3.21 and 9.53 µg/mL. The results demonstrate remarkable cytotoxic activity against the three human tumor cell lines studied, and in the future, further analyses could demonstrate the excellent potential of C. scariosus EO as an antitumor agent.

Anticancer Properties of Different Varieties of Date Palm (Phoenix dactylifera L.) Leaf Extracts in Human Tumor Cells: a Comparative Study.

Plant polyphenols are nutraceutical components with relevant biological effects on human health. They act against development of several diseases including cancer. In this study, the methanolic extracts of four date palm Phoenix dactylifera leaves (Deglet Noor (DN), Barhee (B), Khalas (KS) and Khunezi (KZ)) collected from south Tunisia were preliminary analyzed for their effects against U87 (human glioblastoma) and MDA-MB-231 (human breast cancer) cell line development. Results showed that Barhee extract (30μg/mL) was the most efficient to reduce the growth of both tumor cells to about 40% (p < 0.05) without inducing cytotoxicity. Significantly, KS, KZ, DN and B extracts (30μg/mL) decreased MDA-MB-231 and U87 cell adhesion towards fibrinogen and fibronectin. Using integrin blocking antibodies, leaf extracts competitively decreased human glioblastoma cell attachment to immobilized antibodies by interfering to αvβ3 and α5β1 integrin receptors. At the same concentration, extracts decreased MDA-MB-23 and U87 cell migration performed with wound healing assay. Particularly, Barhee and Deglet Noor leaf extracts (30μg/mL) significantly reduced U87 cell invasion by 52.92% (p < 0.01) and 74.56% (p < 0.01), respectively. Collegially, our findings revealed beneficial proprieties of four varieties of date palm leaf especially those displayed by DN and B extracts that may serve as active candidates against human glioblastoma and breast cancer progression.