Anti-proliferative and apoptotic effects of oleuropein and hydroxytyrosol on human breast cancer MCF-7 cells.
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ABSTRACT:
SUBMITTER: Han J
PROVIDER: S-EPMC2677148 | biostudies-other | 2009 Jan
REPOSITORIES: biostudies-other
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Project description:This study was designed to search for novel anti-cancer compounds from natural plants. The 70% ethanolic extract from the rizhomes of Cimicifuga dahurica (Turcz.) Maxim. (Ranunculaceae) was found to possess significant in vitro anti-proliferative effects on MCF-7 breast cancer cells. A phytochemical investigation using assay-guided fractionation of the ethanolic extract of C. dahurica resulted in the isolation of one new phenolic amide glycoside 3, two new lignan glycosides 4 and 7, one new 9,19-cycloartane triterpenoid glycoside 6, and thirteen known constituents 1, 2, 5, and 8⁻17. The structures of 3, 4, 6, and 7 were established using contemporary NMR methods and from their HRESIMS data. The anti-proliferative effects of isolated compounds were evaluated using the BrdU-proliferation kit. Five among the 17 isolated compounds showed significant anti-proliferative effects (p ≤ 0.05), wherein compound 7 showed the most significant anti-proliferative and cell cycle arresting effect (p ≤ 0.05) which followed a dose dependent manner. Western blot protein expression analysis showed a down expression of c-Myc and cyclin D1 which further elucidated the anti-proliferation mechanism of compound 7 while apoptotic effects were found in association with Bcl-2 family protein expression variations. Conclusively this study reports the isolation and identification of 17 compounds from C. dahurica, including four novel molecules, in addition to the fact that compound 7 possesses significant anti-proliferative and apoptotic effects in vitro that may require further exploration.
| S-EPMC6102574 | biostudies-literature
Project description:PurposeAnti-cancer and anti-migration effects of lupeol as a biological pentacyclic triterpenoid were investigated individually and in combination with Doxorubicin (DOX) on MCF-7 and MDA-MB-231 breast cancer cells and human foreskin fibroblasts.MethodsTo uncover the anticancer effect of lupeol and the impact of its combination with DOX, cell viability and scratch assays and dual acridine-orange apoptotic staining were performed. Moreover, the expression of proapoptotic caspase-3 and metastasis-related MMP-9 at the mRNA and protein levels was analyzed using qPCR and western blot techniques.ResultsLupeol synergistically increased the anti-proliferative effect of DOX with IC50 values of 42.55, 62.24 and 65.9 μM on MCF-7, MDA-MB-231 and HFF cells, respectively. Lupeol reduced the cell migration and lowered the DOX-induced cell migration, significantly (p < 0.05). The number of apoptotic cells elevated significantly (p < 0.05) when cancer cells were treated with the combination of lupeol and DOX. Lupeol individually and in combination with DOX up-regulated the expression of caspase-3. The proposed combination therapy synergized (3-4 fold) the down-regulation of MMP-9 expression in MCF-7 and MDA-MB-231 cells.ConclusionOur results indicate that lupeol could be considered as an anticancer agent and anticancer adjuvant in breast cancer-therapy. The anticancer properties of lupeol attribute to its antiproliferative, antimigrative and apoptotic effects.
| S-EPMC9114251 | biostudies-literature
Project description:Lichens are stable symbiotic associations between fungus and algae and/or cyanobacteria that have different biological activities. Around 60% of anti-cancer drugs are derived from natural resources including plants, fungi, sea creatures, and lichens. This project aims to identify the apoptotic effects and proliferative properties of extracts of Bryoria capillaris (Ach.) Brodo & D.Hawksw, Cladonia fimbriata (L.) Fr., Evernia divaricata (L.) Ach., Hypogymnia tubulosa (Schaer.) Hav., Lobaria pulmonaria (L.) Hoffm., and Usnea florida (L.) Weber ex Wigg. lichen species on prostate cancer cells. Lichen extracts were performed by ethanol, methanol, and acetone separately by using the Soxhlet apparatus and the effects of the extracts on cell viability, proliferation, and apoptosis were measured with the utilization of MTT, LDH assay, Annexin V assay, and Western Blot. Findings of our study revealed a positive correlation between the elevation of cell sensitivity and the increase in the treatment doses of the extract in that higher doses applied reverberate to higher cell sensitivity. A similar correlation was also identified between cell sensitivity elevation and the duration of the treatment. Evidence in our study have shown the existence of an anti-proliferative effect in the extracts of Bryoria capillaris, Evernia divaricata (L.) Ach., Hypogymnia tubulosa (Schaer.) Hav., Lobaria pulmonaria (L.) Hoffm., and Usnea florida (L.) Weber ex Wigg., while a similar effect was not observed in the extracts of Cladonia fimbriata. Evernia divaricata induced anti-proliferative and apoptotic effects in PC-3 cells, which induced apoptotic cell death by both extrinsic and intrinsic pathways. Hypogymnia tubulosa has been shown to have anti-proliferative and apoptotic effects in all extractions methods and our findings identified that both the percentage of the apoptotic cells and apoptotic protein expressions recorded an increase at lower treatment concentrations. Although Lobaria pulmonaria is known to have significant cytotoxic effects, we did not observe a decrease in cell proliferation. Indeed, proliferation marker proliferating cell nuclear antigen (PCNA) protein expression levels have shown an increase in all extracts, while Usnea florida exhibited apoptosis induction and slight proliferation reduction in extract treatments with lower concentrations. We tested 18 extracts of six lichen species during our study. Of these, Evernia divaricata and Hypogymnia tubulosa demonstrated significant apoptotic activity on prostate cancer cells including at low concentrations, which implies that it is worth pursuing the biologically active lead compounds of these extracts on prostate cancer in vitro. Further corroboratory studies are needed to validate the relative potential of these extracts as anti-metastatic and anti-tumorigenic agents.
| S-EPMC7527208 | biostudies-literature
Project description:Resveratrol (RSV), a natural compound present in the skin and seeds of red grapes, is considered a phytoestrogen and has structural similarity to the synthetic estrogen diethylstilbestrol. RSV inhibits tumor cell growth in estrogen receptor-positive (ER+) and negative (ER-) breast cancer cell lines resulting in cell specific regulation of the G1/S and G2/M stages of the cell cycle. However apoptotic cell death was only observed in ER+ MCF-7 cells. In this study, we designed and synthesized boronic acid derivative of RSV and evaluated their biological effects on ER+ MCF-7 breast cancer cells. The trans-4 analog inhibited the growth of MCF-7 cells and is not a substrate for p-glycoprotein. The trans-4 analog induces G1 cell cycle arrest, which coincides with marked inhibition of G1 cell cycle proteins and a greater pro-apoptotic effect. Finally, the trans-4 analog had no effect on the estrogen-stimulated growth of MCF-7 cells. Our results demonstrate that the trans-4 analog inhibits MCF-7 breast cancer cells by a different mechanism of action than that of RSV (S-phase arrest), and provides a new class of novel boronic acids of RSV that inhibit breast cancer cell growth.
| S-EPMC3679116 | biostudies-literature
Project description:BackgroundIt has been demonstrated that platycodin D (PD) exhibits anti-cancer activities. This study aims to investigate the anti-proliferative effects of the combination of PD and doxorubicin (DOX) on human breast cancer cells (MCF-7 and MDA-MB-231 cells).MethodsThe anti-proliferative effects of different dosages of PD, DOX, and PD + DOX on MCF-7 and MDA-MB-231 cells were determined by the MTT assay. The 10 μM PD, 5 μM DOX, and 10 μM PD + 5 μM DOX induced-protein expression of apoptosis-related molecules on MCF-7 and MDA-MB-231 cells were detected by western blot. The 10 μM PD, 5 μM DOX and 10 μM PD + 5 μM DOX-induced mitochondrial membrane potential changes on MCF-7 and MDA-MB-231 cells were stained with JC-1 before visual determination. The intracellular accumulations of DOX, induced by 10 μM PD, 5 μM DOX and 10 μM PD + 5 μM DOX, were detected by flow cytometry.ResultsPD enhanced anti-cancer activities of DOX were observed in both MCF-7 and MDA-MB-231 cell lines. Compared with mono treatment, the combined treatment increased the protein expression of cleaved poly (ADP-ribose) polymerase and decreased the mitochondrial membrane potential. The combined treatment with PD did not obviously increase the accumulation of DOX in MCF-7 cells (1.66 ± 0.13 in DOX-treated group, and 1.69 ± 0.06 in PD + DOX-treated group, P = 0.76), but it significantly increased the accumulation of DOX in MDA-MB-231 cells (1.76 ± 0.17 in DOX-treated group, 2.09 ± 0.02 in PD + DOX-treated group, P = 0.027).ConclusionThe combined treatment of DOX and PD exhibited stronger anti-proliferative effects on MCF-7 and MDA-MB-231 cells than DOX and PD treatment did.
| S-EPMC4075934 | biostudies-literature
Project description:Molecular targeted therapy has shown promise as a treatment for advanced hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, recently received FDA approval for the treatment of advanced HCC. However, although sorafenib is well tolerated, concern for its safety has been expressed. Celecoxib (Celebrex®) is a selective cyclooxygenase-2 (COX-2) inhibitor which exhibits antitumor effects in human HCC cells. The present study examined the interaction between celecoxib and sorafenib in two human liver tumor cell lines HepG2 and Huh7. Our data showed that each inhibitor alone reduced cell growth and the combination of celecoxib with sorafenib synergistically inhibited cell growth and increased apoptosis. To better understand the molecular mechanisms underlying the synergistic antitumor activity of the combination, we investigated the expression profile of the combination-treated liver cancer cell lines using microarray analysis. Combination treatment significantly altered expression levels of 1,986 and 2,483 transcripts in HepG2 and Huh7 cells, respectively. Genes functionally involved in cell death, signal transduction and regulation of transcription were predominantly up-regulated, while genes implicated in metabolism, cell-cycle control and DNA replication and repair were mainly down-regulated upon treatment. However, combination-treated HCC cell lines displayed specificity in the expression and activity of crucial factors involved in hepatocarcinogenesis. The altered expression of some of these genes was confirmed by semi-quantitative and quantitative RT-PCR and by Western blotting. Many novel genes emerged from our transcriptomic analyses, and further functional analyses may determine whether these genes can serve as potential molecular targets for more effective anti-HCC strategies.
| S-EPMC3680460 | biostudies-literature
Project description:Finding intracellular pathways and molecules that can prevent the proliferation of colon cancer cells can provide significant bases for developing treatments for this disease. Ostreolysin (Oly) is a protein found in the mushroom Pleurotus ostreatus, and we have produced a recombinant version of this protein (rOly).We measured the viability of several colon cancer cells treated with rOly. Xenografts and syngeneic colon cancer cells were injected into in vivo mouse models, which were then treated with this recombinant protein.rOly treatment induced a significant reduction in viability of human and mouse colon cancer cells. In contrast, there was no reduction in the viability of normal epithelial cells from the small intestine. In the search for cellular targets of rOly, we showed that it enhances the anti-proliferative activity of drugs targeting cellular tubulin. This was accompanied by a reduction in the weight and volume of tumours in mice injected with rOly as compared to their respective control mice in two in vivo models.Our results advance the functional understanding of rOly as a potential anti-cancer treatment associated with pro-apoptotic activities preferentially targeting colon cancer cells.
| S-EPMC5438697 | biostudies-literature
Project description:BackgroundJatropha curcas (JCP1), Pyrenacantha staudtii (PS), Picralima nitida (ZI) and Jatropha gossypifolia (JCP2) are plants used in the African folklore for the treatment of various cancers.MethodsThis study investigated the in vitro anticancer effects of the ethanol extracts against human epithelial MCF-7 breast cancer cells in a dose-dependent manner (1-50 μg/ml) by using cell cycle analysis, viability assay, annexin V/PI staining, TUNEL method and expression determination of apoptotic and adhesion relevant proteins. Adhesion processes were monitored by detachment via flow cytometry, β1-integrin expression and formation of the actin cytoskeleton.ResultsThe three extracts, termed PS, JCP1 and JCP2 at a concentration of 10 μg/ml induced cell death in MCF-7 breast cancer cells verified by high amounts of PI-positive cells in the cell cycle analysis, Annexin V/PI staining and DNA fragmentation measurements. In parallel cell detachment was accompanied by decreased β1- integrin expression and phosphorylation of the focal adhesion kinase at Tyr397. ZI extract was the exception by the increasing β1-integrin expression and strengthening the cortical actin cytoskeleton. However, all four plant extracts mediated strong anti-cancer properties with IC50 values between 23-38 μg/ml.ConclusionPS, JCP1 and JCP2 were found to be very active against MCF-7 cells by inducing anoikis and therefore possessing vast potential as medicinal drugs especially in estrogen receptor positive breast cancer treatment. ZI mediated their anti-cancer action by different signaling mechanisms which should be analyzed in future studies. Our results further supported the idea that medicinal plants can be promising sources of putative anticancer agents.
| S-EPMC4177160 | biostudies-literature
Project description:ONC201 was initially identified as an inducer of cell death through the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway. The compound is currently being tested in patients with hematological malignancies and solid tumors, including those of the breast. We investigated strategies to convert the response of breast cancers to ONC201 from anti-proliferative to apoptotic. ONC201 treatment upregulates TRAIL and primes TRAIL-resistant non-triple negative breast cancer (TNBC) cells to undergo cell death through the extrinsic pathway. Remarkably, the addition of exogenous recombinant human TRAIL (rhTRAIL) converts the response of TRAIL-resistant non-TNBC cells to ONC201 from anti-proliferative to apoptotic in a death receptor 5 (DR5)-dependent manner in vitro. Importantly, normal fibroblasts do not undergo apoptosis following rhTRAIL plus ONC201. In vivo, MDA-MB-361 tumor growth rate is significantly reduced following treatment with a combination of ONC201 and rhTRAIL as compared to control tumors. Natural killer (NK) cells which use TRAIL to kill DR5-expressing cancer cells, exhibit greater cytotoxicity against ONC201-treated breast cancer cells compared to controls. rhTRAIL also converts the response of cells from other tumor types to ONC201 from anti-proliferative to apoptotic. A monoclonal DR5-agonistic antibody converts the response of non-TNBC cells to ONC201 from anti-proliferative to apoptotic. Our findings describe a novel therapeutic strategy that potently converts the response of a cancer cell to ONC201 from anti-proliferative to apoptotic. This approach may be clinically relevant and has potential to induce tumor regression of patient tumors with relative resistance to ONC201 monotherapy.
| S-EPMC7584235 | biostudies-literature
Project description:: Background and objectives: Previous studies have shown anti-tumor activity of quercetin (QT). However, the low bioavailability of QT has restricted its use. This study aimed to assess the toxic effect of QT encapsulated in solid lipid nanoparticles (QT-SLNs) on the growth of MCF-7 human breast cancer cells. Materials and Methods: MCF-7 and MCF-10A (non-tumorigenic cell line) cell lines treated with 25 µmol/mL of QT or QT-SLNs for 48 h. Cell viability, colony formation, oxidative stress, and apoptosis were evaluated to determine the toxic effects of the QT-SLNs. Results: The QT-SLNs with appropriate characteristics (particle size of 85.5 nm, a zeta potential of -22.5 and encapsulation efficiency of 97.6%) were prepared. The QT-SLNs showed sustained QT release until 48 h. Cytotoxicity assessments indicated that QT-SLNs inhibited MCF-7 cells growth with a low IC50 (50% inhibitory concentration) value, compared to the free QT. QT-SLNs induced a significant decrease in the viability and proliferation of MCF-7 cells, compared to the free QT. QT-SLN significantly increased reactive oxygen species (ROS) level and MDA contents and significantly decreased antioxidant enzyme activity in the MCF-7 cells. Following QT-SLNs treatment, the expression of the Bcl-2 protein significantly decreased, whereas Bx expression showed a significant increase in comparison with free QT-treated cells. Furthermore, The QT-SLNs significantly increased apoptotic and necrotic indexes in MCF-7 cells. Viability, proliferation, oxidative stress and apoptosis of MCF-10A cells were not affected by QT or QT-SLNs. Conclusion: According to the results of this study, SLN significantly enhanced the toxic effect of QT against human breast cancer cells.
| S-EPMC6524048 | biostudies-literature