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Anti-proliferative activities of Byrsocarpus coccineus Schum. and Thonn. (Connaraceae) using ovarian cancer cell lines.

ABSTRACT: BACKGROUND:Ovarian cancer (OvCa) is one of the most lethal tumors of gynecologic malignancies, due to lack of early detection, and a high rate of metastasis. The standard treatment for OvCa is surgery and cytotoxic chemotherapy. However, to overcome the high cost and side effects of these treatments, medicinal plants are widely used in developing countries to treat OvCa. Byrsocarpus coccineus plant preparation has been administered to patients traditionally in the management of tumors in Nigeria. In this study, we investigated the anti-proliferative effects of B. coccineus ethanol leaf extract against OVCAR-3 and SW 626 OvCa cell lines. After the treatment of the two cell lines with the extracts, analyses were carried out to determine inhibition of proliferation and expression of cell cycle markers, pro-apoptotic, and anti-apoptotic markers. RESULTS:Results showed that B. coccineus ethanol leaf extract, significantly inhibited cell migration and colony formation in OVCAR-3 and SW 626 treated cells in a dose-dependent manner. Results also show that B. coccineus ethanol leaf extract modulated the expression of tumor suppressor gene (p53), cell cycle progression, pro- and anti-apoptotic gene, and the pro-inflammatory cytokines. CONCLUSIONS:These results suggest that B. coccineus have anti-proliferative properties and could induce apoptosis. Further investigation will be carried out to isolate bioactive compounds for the treatment of ovarian cancer.

SUBMITTER: Ukwade CE

PROVIDER: S-EPMC7374866 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Anti-proliferative activities of Byrsocarpus coccineus Schum. and Thonn. (Connaraceae) using ovarian cancer cell lines.

Ukwade Caroline E CE Ebuehi Osaretin A T OAT Adisa Rahmat A RA Singh Santosh K SK Singh Rajesh R

Journal of ovarian research 20200721 1

<h4>Background</h4>Ovarian cancer (OvCa) is one of the most lethal tumors of gynecologic malignancies, due to lack of early detection, and a high rate of metastasis. The standard treatment for OvCa is surgery and cytotoxic chemotherapy. However, to overcome the high cost and side effects of these treatments, medicinal plants are widely used in developing countries to treat OvCa. Byrsocarpus coccineus plant preparation has been administered to patients traditionally in the management of tumors in ...[more]

PMID: 32693841

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Project description:BackgroundPhyllanthus amarus has been used widely in various traditional medicines to treat swelling, sores, jaundice, inflammatory diseases, kidney disorders, diabetes and viral hepatitis, while its pharmacological and biochemical mechanisms underlying its anti-inflammatory properties have not been well investigated. The present study was carried out to investigate the effects of 80% ethanolic extract of P. amarus on pro-inflammatory mediators release in nuclear factor-kappa B (NF-?B), mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase/Akt (PI3K-Akt) signaling activation in lipopolysaccharide (LPS)-induced U937 human macrophages.MethodsThe release of prostaglandin E2 (PGE2) and pro-inflammatory cytokines, tumor necrosis factor (TNF)-? and interleukin (IL)-1? in a culture supernatant was determined by ELISA. Determination of cyclooxygenase-2 (COX-2) protein and the activation of MAPKs molecules (JNK, ERK and p38 MAPK), NF-?B and Akt in LPS-induced U937 human macrophages were investigated by immunoblot technique. The relative gene expression levels of COX-2 and pro-inflammatory cytokines were measured by using qRT-PCR. The major metabolites of P. amarus were qualitatively and quantitatively analyzed in the extract by using validated reversed-phase high performance liquid chromatography (HPLC) methods.ResultsP. amarus extract significantly inhibited the production of pro-inflammatory mediators (TNF-?, IL-1?, PGE2) and COX-2 protein expression in LPS-induced U937 human macrophages. P. amarus-pretreatment also significantly downregulated the increased mRNA transcription of pro-inflammatory markers (TNF-?, IL-1?, and COX-2) in respective LPS-induced U937 macrophages. It downregulated the phosphorylation of NF-?B (p65), I?B?, and IKK?/? and restored the degradation of I?B?, and attenuated the expression of Akt, JNK, ERK, and p38 MAPKs phosphorylation in a dose-dependent manner. P. amarus extract also downregulated the expression of upstream signaling molecules, TLR4 and MyD88, which play major role in activation of NF-?B, MAPK and PI3K-Akt signaling pathways. The quantitative amounts of lignans, phyllanthin, hypophyllahtin and niranthin, and polyphenols, gallic acid, geraniin, corilagin, and ellagic acid in the extract were determined by HPLC analysis.ConclusionThe study revealed that P. amarus targeted the NF-?B, MAPK and PI3K-Akt signaling pathways to exert its anti- inflammatory effects by downregulating the prospective inflammatory signaling mediators.

Project description:Objective:Sea cucumbers are considered among the most important functional foods. Following bioassay guided fractionation, we assessed the anti-proliferative and anti-inflammatory activities of Holothuria polii (H. polii) extracts. Methods:Sea cucumber ethanolic extract and the partially purified aqueous fractions were assessed for their anti-proliferative activities. These latter bioactivities were evaluated in the highly invasive MDA-MB-231 human breast cancer cells in two-dimensional and three-dimensional cultures using trypan blue exclusion assay. The tumor-suppressive effects of sea cucumber ethanolic extract and aqueous fractions were assayed by measuring the trans-well invasion of MDA-MB-231 cells and the expression of some epithelial mesenchymal transition markers using quantitative reverse-transcription polymerase chain reaction and western blot analysis. The anti-inflammatory activity of the aqueous fraction was tested by measuring the secreted levels of interleukin-6, nitric oxide, and matrix metalloproteinase 9 in endotoxin-induced mammary epithelial SCp2 cells and interleukin-1? in phorbol-12-myristate-13-acetate-activated human monocytic THP-1 cells. Results:Sea cucumber ethanolic extract and the aqueous fraction significantly decreased the proliferation of MDA-MB-231 cells by more than 50% at similar and noncytotoxic concentrations and caused an arrest in the S-phase of the cell cycle of treated cells. In contrast, petroleum ether, chloroform, ethyl acetate, and n-butanol organic fractions did not show any significant activity. Furthermore, sea cucumber ethanolic extract and aqueous fraction reduced the proliferation of MDA-MB-231 cells in three-dimensional cultures by more than 60% at noncytotoxic concentrations. In addition, treatment with these concentrations resulted in the loss of stellate outgrowths in favor of spherical aggregates and a 30% decrease in invasive properties. Both sea cucumber ethanolic extract and aqueous decreased the transcription of vimentin and the protein expression levels of vimentin and N-cadherin in three-dimensional cultures. The aqueous fraction decreased the levels of inflammatory markers interleukin-6, nitric oxide, and matrix metalloproteinase 9 in the mouse mammary SCp2 cells, and the level of interleukin-1? produced by phorbol-12-myristate-13-acetate-activated THP-1 human monocytic cells. Conclusion:The data reveal for the first time promising anti-proliferative and anti-inflammatory activities in H. polii water extract in two-dimensional and three-dimensional culture models.

Dataset Information

Anti-proliferative activities of Byrsocarpus coccineus Schum. and Thonn. (Connaraceae) using ovarian cancer cell lines.

Publications

Anti-proliferative activities of Byrsocarpus coccineus Schum. and Thonn. (Connaraceae) using ovarian cancer cell lines.

Similar Datasets

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