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Therapeutic effect of Arthrocnemum machrostachyum methanolic extract on Ehrlich solid tumor in mice.

ABSTRACT: BACKGROUND:The anti-cancer effect of the halophyte Arthrocnemum indicum, a member of Arthrocnemum family of salt-tolerant plants, was evaluated against colorectal cancer cell, CaCo2. However, the anti-cancer effect of another halophyte Arthrocnemum machrostachyum was not investigated yet. Herein, the anticancer effect of A. machrostachyum methanolic extract (AME) was evaluated against Ehrlich solid tumor (EST) in mice and the potential mechanism of action was also studied. METHODS:Male Swiss albino mice (n?=?28) were randomly divided into 4 groups (n?=?7/group). Group 1 (negative control group); group 2 (EST) injected intramuscularly by 0.2?mL Ehrlich ascitic carcinoma (2?×?106 cells); and groups 3 and 4 injected intratumorally with AME (180 and 360?mg/kg body weight, respectively) at D12 trice weekly for 2?weeks. Gene expression, protein expression, DNA damage, and TNFa level in tumors were determined by real-time PCR, western blot, comet assay, and Elisa, respectively. RESULTS:Treatment with AME induced anti-tumor effects against EST as indicated by 1) notable reduction in tumor size; 2) elevation in tissue necrosis and apoptosis, as confirmed histologically; 3) increased DNA fragmentation; 4) decreased expression of the apoptotic genes (p53, Bax and caspase 3), and increased expression of the anti-apoptotic marker Bcl2; 5) significantly upregulated cell cycle regulatory genes Cdc2 and connexin26, and; 6) decreased TNFa levels in tumor tissues. Interestingly, a high dose of AME exhibited a more potent anti-tumor effect against EST. CONCLUSION:These findings indicate that AME has a potent antitumor effect against EST and could be used as an adjuvant to anticancer drugs to combat tumor, but after application of further confirmatory clinical trials.

SUBMITTER: Sharawi ZW

PROVIDER: S-EPMC7245743 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Therapeutic effect of Arthrocnemum machrostachyum methanolic extract on Ehrlich solid tumor in mice.

Sharawi Zeina W ZW Sharawi Zeina W ZW

BMC complementary medicine and therapies 20200524 1

<h4>Background</h4>The anti-cancer effect of the halophyte Arthrocnemum indicum, a member of Arthrocnemum family of salt-tolerant plants, was evaluated against colorectal cancer cell, CaCo2. However, the anti-cancer effect of another halophyte Arthrocnemum machrostachyum was not investigated yet. Herein, the anticancer effect of A. machrostachyum methanolic extract (AME) was evaluated against Ehrlich solid tumor (EST) in mice and the potential mechanism of action was also studied.<h4>Methods</h4 ...[more]

PMID: 32448237

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Project description:Background and objectivesESC or Ehrlich solid carcinoma is a type of tumor originating from a spontaneous mammary adenocarcinoma in mice. It is a highly aggressive and fast-growing carcinoma that can create a solid mass when inserted under the skin. Its solid, undifferentiated form makes it an ideal model for researching cancer biology, tumor immunology, and testing various anti-cancer treatments. Additionally, arctiin has multiple beneficial properties, such as anti-proliferative, anti-oxidative, anti-adipogenic, and anti-bacterial. This study aimed to explore the potential anti-cancer benefits of arctiin in rats with ESC while also analyzing its effects on cell fibrosis markers, tumor cell migration, and inflammasome pathways.MethodsRats were given a tumor in their left hind limb via an intramuscular injection consisting of 2×106 cells. After eight days, some of the rats received a daily oral dose of 30 mg/kg of arctiin for three weeks. Muscle samples were observed under an electron microscope or stained with hematoxylin/eosin. Additionally, gene expression and protein levels of toll-like receptor 4 (TLR4), NLR family pyrin domain containing 3 (NLRP3), signal transducer and activator of transcription 3 (STAT3), transforming growth factor (TGF)-β, endothelial growth factor (VEGF), and cyclin D1 were assessed in another part of the muscle samples.ResultsWhen ESC rats were given arctiin as a treatment, their mean survival time increased and their tumor volume and weight decreased. Additionally, when tumor tissue was examined under an electron microscope, it showed signs of pleomorphic cells, necrosis, nuclear fragmentation, membrane damage with cytoplasmic content spilling, and loss of cellular junction. The stained sections with hematoxylin/eosin showed a dense cellular mass and compressed, degenerated, and atrophied muscle. However, treatment with arctiin improved all these effects. Finally, the expression of TLR4, NLRP3, STAT3, TGF-β, VEGF, and cyclin D1 was significantly reduced with arctiin treatment.ConclusionsThrough the use of arctiin, tumor size and weight were effectively reduced, leading to an increase in the average survival time of rats and an improvement in muscle structure. Additional research has shown that arctiin is able to suppress inflammation, fibrosis, and the migration of tumor cells by inhibiting STAT3, TGF-β1, TLR4, NLRP3, VEGF, and cyclin D1.

Project description:BackgroundThevetia peruviana (Pers.) K. Schum or Cascabela peruviana (L.) Lippold (commonly known as ayoyote, codo de fraile, lucky nut, or yellow oleander), native to Mexico and Central America, is a medicinal plant used traditionally to cure diseases like ulcers, scabies, hemorrhoids and dissolve tumors. The purpose of this study was to evaluate the cytotoxic, antiproliferative and apoptotic activity of methanolic extract of T. peruviana fruits on human cancer cell lines.MethodsThe cytotoxic activity of T. peruviana methanolic extract was carried out on human breast, colorectal, prostate and lung cancer cell lines and non-tumorigenic control cells (fibroblast and Vero), using the MTT assay. For proliferation and motility, clonogenic and wound-healing assays were performed. Morphological alterations were monitored by trypan blue exclusion, as well as DNA fragmentation and AO/EB double staining was performed to evaluate apoptosis. The extract was separated using flash chromatography, and the resulting fractions were evaluated on colorectal cancer cells for their cytotoxic activity. The active fractions were further analyzed through mass spectrometry.ResultsThe T. peruviana methanolic extract exhibited cytotoxic activity on four human cancer cell lines: prostate, breast, colorectal and lung, with values of IC50 1.91 ± 0.76, 5.78 ± 2.12, 6.30 ± 4.45 and 12.04 ± 3.43 μg/mL, respectively. The extract caused a significant reduction of cell motility and colony formation on all evaluated cancer cell lines. In addition, morphological examination displayed cell size reduction, membrane blebbing and detachment of cells, compared to non-treated cancer cell lines. The T. peruviana extract induced apoptotic cell death, which was confirmed by DNA fragmentation and AO/EB double staining. Fractions 4 and 5 showed the most effective cytotoxic activity and their MS analysis revealed the presence of the secondary metabolites: thevetiaflavone and cardiac glycosides.ConclusionT. peruviana extract has potential as natural anti-cancer product with critical effects in the proliferation, motility, and adhesion of human breast and colorectal cancer cells, and apoptosis induction in human prostate and lung cancer cell lines, with minimal effects on non-tumorigenic cell lines.

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Therapeutic effect of Arthrocnemum machrostachyum methanolic extract on Ehrlich solid tumor in mice.

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Therapeutic effect of Arthrocnemum machrostachyum methanolic extract on Ehrlich solid tumor in mice.

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