Natural prenylated xanthones as potential inhibitors of PI3k/Akt/mTOR pathway in triple negative breast cancer cells

Planta Medica ◽  
2021 ◽  
Author(s):  
Thi Thu Ha Nguyen ◽  
Zhao Qu ◽  
Van Tuyen Nguyen ◽  
Thanh Tra Nguyen ◽  
Thi Tu Anh Le ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Inhibitory Effect ◽  
Positive Control ◽  
Phosphorylated Form ◽  
Anti Cancer ◽  
M Phase ◽  
Potential Inhibitors ◽  
Leading Compounds

Three prenylated xanthones, garcinone E (1), bannaxanthone D (2) and bannanxanthone E (3) were isolated from the leaves of Garcinia mckeaniana Graib. Their structures were elucidated by spectral methods and compared with literature data. To evaluate their anti-proliferative effects in tumor cells, firstly, cisplatin was used as a positive control and the effects of compound 1-3 were determined by performing MTT assay in MDA-MB-231, CNE-2 and A549 cancer cells. The results showed compound 1-3 exhibited stronger inhibitory effect than cisplatin in MDA-MB-231. Further effects of compound 1-3 in TNBC MDA-MB-231 and MDA-MB-468 cells were examined by performing cell cycle and apoptosis assays. The results indicated that compound 1-3 had ability to arrest cell cycle at G2/M phase and induce apoptosis. Furthermore, compound 2 significantly down-regulated PI3K, Akt and mTOR levels in both total proteins and phosphorylated form, which is its potential anti-cancer mechanism. These findings indicated that those prenylated xanthones might serve as promising leading compounds for the development of anticancer drug for TNBC.

[(2-Phenylindol-3-yl)methylene]propanedinitriles inhibit the growth of breast cancer cells by cell cycle arrest in G2/M phase and apoptosis

2007 ◽  
Vol 15 (23) ◽  
pp. 7368-7379 ◽  
Author(s):  
Michaela Pojarová ◽  
Doris Kaufmann ◽  
Robert Gastpar ◽  
Tsuyuki Nishino ◽  
Przemyslaw Reszka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cycle Arrest ◽  
M Phase

scholarly journals A Flavone Constituent from Myoporum bontioides Induces M-Phase Cell Cycle Arrest of MCF-7 Breast Cancer Cells

Molecules ◽  
2017 ◽  
Vol 22 (3) ◽  
pp. 472 ◽  
Author(s):  
Jing-Ru Weng ◽  
Li-Yuan Bai ◽  
Wei-Yu Lin ◽  
Chang-Fang Chiu ◽  
Yu-Chang Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Phase Cell ◽  
Cycle Arrest ◽  
M Phase ◽  
Mcf 7

scholarly journals Antibody–drug nanoparticle induces synergistic treatment efficacies in HER2 positive breast cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Muhammad Raisul Abedin ◽  
Kaitlyne Powers ◽  
Rachel Aiardo ◽  
Dibbya Barua ◽  
Sutapa Barua
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Anti Cancer ◽  
Antibody Drug ◽  
Positive Breast Cancer

AbstractChemotherapeutic drugs suffer from non-specific binding, undesired toxicity, and poor blood circulation which contribute to poor therapeutic efficacy. In this study, antibody–drug nanoparticles (ADNs) are engineered by synthesizing pure anti-cancer drug nanorods (NRs) in the core of nanoparticles with a therapeutic monoclonal antibody, Trastuzumab on the surface of NRs for specific targeting and synergistic treatments of human epidermal growth factor receptor 2 (HER2) positive breast cancer cells. ADNs were designed by first synthesizing ~ 95 nm diameter × ~ 500 nm long paclitaxel (PTX) NRs using the nanoprecipitation method. The surface of PTXNRs was functionalized at 2′ OH nucleophilic site using carbonyldiimidazole and conjugated to TTZ through the lysine residue interaction forming PTXNR-TTZ conjugates (ADNs). The size, shape, and surface charge of ADNs were characterized using scanning electron microscopy (SEM), SEM, and zeta potential, respectively. Using fluorophore labeling and response surface analysis, the percentage conjugation efficiency was found > 95% with a PTX to TTZ mass ratio of 4 (molar ratio ≈ 682). In vitro therapeutic efficiency of PTXNR-TTZ was evaluated in two HER2 positive breast cancer cell lines: BT-474 and SK-BR-3, and a HER2 negative MDA-MB-231 breast cancer cell using MTT assay. PTXNR-TTZ inhibited > 80% of BT-474 and SK-BR-3 cells at a higher efficiency than individual PTX and TTZ treatments alone after 72 h. A combination index analysis indicated a synergistic combination of PTXNR-TTZ compared with the doses of single-drug treatment. Relatively lower cytotoxicity was observed in MCF-10A human breast epithelial cell control. The molecular mechanisms of PTXNR-TTZ were investigated using cell cycle and Western blot analyses. The cell cycle analysis showed PTXNR-TTZ arrested > 80% of BT-474 breast cancer cells in the G2/M phase, while > 70% of untreated cells were found in the G0/G1 phase indicating that G2/M arrest induced apoptosis. A similar percentage of G2/M arrested cells was found to induce caspase-dependent apoptosis in PTXNR-TTZ treated BT-474 cells as revealed using Western blot analysis. PTXNR-TTZ treated BT-474 cells showed ~ 1.3, 1.4, and 1.6-fold higher expressions of cleaved caspase-9, cytochrome C, and cleaved caspase-3, respectively than untreated cells, indicating up-regulation of caspase-dependent activation of apoptotic pathways. The PTXNR-TTZ ADN represents a novel nanoparticle design that holds promise for targeted and efficient anti-cancer therapy by selective targeting and cancer cell death via apoptosis and mitotic cell cycle arrest.

Lidocaine Inhibits Breast Cancer Cell Proliferation and Induces Cell Apoptosis via Regulating MEK/ERK and PI3K/AKT Signalling Pathways

2021 ◽  
Author(s):  
Xu Wang ◽  
Shi-Hang Xi ◽  
Qin Li ◽  
ting han
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Flow Cytometric Analysis ◽  
Inhibitory Effect ◽  
Potential Candidate ◽  
Protein Levels ◽  
M Phase ◽  
Mcf 7

Abstract Background: Lidocaine is a commonly used local anesthetic in clinic, which is mainly used for anesthesia and analgesia. Lidocaine has been recently found to have an inhibitory effect on a variety of cancers.Materials and Methods: We used MTT assay and cell proliferation assay to detect the inhibition of lidocaine on proliferation of MCF-7 and MDA-MB-231 breast cancer cells. Flow cytometric analysis was used to detect cell cycle and apoptosis. Western blot was used to detect protein levels of cyclin-dependent kinase 1(CDK1) ,cyclinB1, BCL2, BCL-XL, p62, LC3B, p-ERK,p-AKT, ERK and AKT.Results: Lidocaine inhibited the proliferation of MCF-7 and MDA-MB-231 breast cancer cells, increased the percentage of G2 / M phase cells , apoptosis and autophagy by reducing the mRNA of CDK1 and cyclinB1, decreasing protein levels of CDK1,cyclinB1,BCL2, BCL-XL, p62, p-ERK and p-AKT protein, and increasing LC3B-II/LC3B-I protein levels.Conclusion: Lidocaine may be a potential candidate for treatment of breast cancer.

scholarly journals Naringenin inhibits human breast cancer cells (MDA-MB-231) by inducing programmed cell death, caspase stimulation, G2/M phase cell cycle arrest and suppresses cancer metastasis

2021 ◽  
Vol 67 (2) ◽  
pp. 8-13
Author(s):  
Zhaozhen Qi ◽  
Shuangxi Kong ◽  
Shunyu Zhao ◽  
Qiu Tang
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Apoptotic Cell ◽  
Flow Cytometric Analysis ◽  
Annexin V ◽  
Cycle Arrest ◽  
Flow Cytometric ◽  
M Phase

The current study was designed to unveil the anticancer effects of naringenin against breast cancer MDA-MB-231 cells. Cytotoxic effects were estimated via MTT viability assay. Clonogenic assay was performed to assess clonogenic potential of MDA-MB-231 cells. Apoptosis was examined via AO/EB staining, quantified via annexin V/PI staining and western blotting was performed to monitor apoptosis allied protein expressions. Cell cycle was analyzed through flow cytometric analysis. Transwell chambers assay was executed for determination of cell migration and cell invasion tendency of MDA-MB-231 breast cancer cells. Results indicated significant anticancer potential of naringenin drug against MDA-MB-231 cells. On evaluation of cell proliferation rate of breast cancer cells by MTT assay, it was observed that naringenin inhibited proliferation rate in dose as well as time dependent manner. AO/EB staining assay revealed potential morphological changes indicating apoptotic cell death. Annexin V/PI staining assay revealed increased apoptotic cell percentage with increased drug doses. The apoptosis inducing potential of naringenin drug was observed to be mediated via caspase activation. Flow cytometric analysis predicted cell cycle arrest at G2/M phase of cell cycle. Further cell migration as well as cell invasion tendency of MDA-MB-231 cells was reduced to minimum upon application of naringenin drug.

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