Cannabinoid Combination Induces Cytoplasmic Vacuolation in MCF-7 Breast Cancer Cells

This study evaluated the synergistic anti-cancer potential of cannabinoid combinations across the MDA-MB-231 and MCF-7 human breast cancer cell lines. Cannabinoids were combined and their synergistic interactions were evaluated using median effect analysis. The most promising cannabinoid combination (C6) consisted of tetrahydrocannabinol, cannabigerol (CBG), cannabinol (CBN), and cannabidiol (CBD), and displayed favorable dose reduction indices and limited cytotoxicity against the non-cancerous breast cell line, MCF-10A. C6 exerted its effects in the MCF-7 cell line by inducing cell cycle arrest in the G2 phase, followed by the induction of apoptosis. Morphological observations indicated the induction of cytoplasmic vacuolation, with further investigation suggesting that the vacuole membrane was derived from the endoplasmic reticulum. In addition, lipid accumulation, increased lysosome size, and significant increases in the endoplasmic reticulum chaperone protein glucose-regulated protein 78 (GRP78) expression were also observed. The selectivity and ability of cannabinoids to halt cancer cell proliferation via pathways resembling apoptosis, autophagy, and paraptosis shows promise for cannabinoid use in standardized breast cancer treatment.

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Compounds From the Root of Pueraria peduncularis (Grah. ex Benth.) Benth. and Their Antitumor Effects

Natural Product Communications ◽

10.1177/1934578x19882521 ◽

2019 ◽

Vol 14 (11) ◽

pp. 1934578X1988252

Author(s):

Huabao Chen ◽

Yong Qian ◽

Xiaomin Zhao ◽

Tianxing Lv ◽

Bin Wang ◽

...

Keyword(s):

Breast Cancer ◽

Lung Adenocarcinoma ◽

Cell Line ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Breast Cancer Cell Lines ◽

Root Extract ◽

Antitumor Effects ◽

Wide Range ◽

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Pueraria peduncularis belongs to the genus Pueraria DC., and has a wide range of medicinal and agricultural values. Previous studies have shown that methanol extracts of P. peduncularis had broad range bioactivities against different pests such as insects, phytopathogens, and snails; however, the specific studies with regard to active compounds against these pests have not been reported. In the current study, we systematically assessed the effects of P. peduncularis root extract against cancer cells, and we also isolated, purified, and analyzed the active ingredients of 8 different compounds from the root of P. peduncularis. To the best of our knowledge, coumestrol (compound 1), lupinalbin A (compound 2), wighteone (compound 6), and erythrinin C (compound 4) were the first isolated from the P. peduncularis root in our study. The extract of the P. peduncularis root had a significantly strong cytotoxic activity on the lung adenocarcinoma cell line A549 (31.0%) and breast cancer cell line MCF-7 (33.0%), respectively. Lupinalbin A (compound 2), erythrinin C (compound 4), pedunsaponin A (compound 7), and pedunsaponin C (compound 8) had more than 40% inhibitory effects on the lung adenocarcinoma line A549. Whereas erythrinin C (compound 4) and pedunsaponin C inhibited more than 47% breast cancer cell lines MCF-7. These results indicate that P. peduncularis is rich in anticancer substances that laid the foundation for a further understanding of P. peduncularis and need to be further explored for other diseases.

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A Combination of an Antimitotic and a Bromodomain 4 Inhibitor Synergistically Inhibits the Metastatic MDA-MB-231 Breast Cancer Cell Line

BioMed Research International ◽

10.1155/2019/1850462 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 1

Author(s):

Thandi Mqoco ◽

André Stander ◽

Anna-Mart Engelbrecht ◽

Anna M Joubert

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cell Line ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Breast Cancer Cells ◽

Chemotherapeutic Agents ◽

Breast Cancer Cell Lines ◽

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Current chemotherapeutic agents have many side effects and are toxic to normal cells, providing impetus to identify agents that can effectively eliminate tumorigenic cells without damaging healthy cells. The aim of this study was to examine whether combining a novel BRD4 inhibitor, ITH-47, with the antimitotic estradiol analogue, ESE-15-ol, would have a synergistic effect on inhibiting the growth of two different breast cancer cell lines in vitro. Our docking and molecular dynamics studies showed that compared to JQ1, ITH-47 showed a similar binding mode with hydrogen bonds forming between the ligand nitrogens of the pyrazole, ASN99, and water of the BRD4 protein. Data from cell growth studies revealed that the GI50 of ITH-47 and ESE-15-ol after 48 hours of exposure was determined to be 15 μM and 70 nM, respectively, in metastatic MDA-MB-231 breast cancer cells. In tumorigenic MCF-7 breast cancer cells, the GI50 of ITH-47 and ESE-15-ol was 75 μM and 60 nM, respectively, after 48 hours of exposure. Furthermore, the combination of 7.5 μM and 14 nM of ITH-47 and ESE-15-ol, respectively, resulted in 50% growth inhibition of MDA-MB-231 cells resulting in a synergistic combination index (CI) of 0.7. Flow cytometry studies revealed that, compared to the control, combination-treated MDA-MB-231 cells had significantly more cells present in the sub-G1 phase and the combination treatment induced apoptosis in the MDA-MB-231 cells. Compared to vehicle-treated cells, the combination-treated cells showed decreased levels of the BRD4, as well as c-Myc protein after 48 hours of exposure. In combination, the selective BRD4 inhibitor, ITH-47, and ESE-15-ol synergistically inhibited the growth of MDA-MB-231 breast cancer cells, but not of the MCF-7 cell line. This study provides evidence that resistance to BRD4 inhibitors may be overcome by combining inhibitors with other compounds, which may have treatment potential for hormone-independent breast cancers.

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Kaurenoic Acid Induces Cell Cycle Arrest and Apoptosis in the MCF‐7 Breast Cancer Cell Line

ChemistrySelect ◽

10.1002/slct.202002638 ◽

2020 ◽

Vol 5 (38) ◽

pp. 11850-11853

Author(s):

Anderson Roberto de Souza ◽

Mona Stefany de Souza Castro ◽

Thiago Olímpio de Souza ◽

Rodrigo Cassio Sola Veneziani ◽

Jairo Kenupp Bastos ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Cell Line ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Breast Cancer Cell Line ◽

Cancer Cell Line ◽

Cycle Arrest ◽

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PRELIMINARY CYTOTOXIC EVALUATION OF Andrographis paniculata IN BREAST CANCER CELL LINES

Jurnal Bioteknologi & Biosains Indonesia (JBBI) ◽

10.29122/jbbi.v2i1.533 ◽

2016 ◽

Vol 2 (1) ◽

pp. 34

Author(s):

Tarwadi . ◽

Churiyah . ◽

Olivia Bunga Pongtuluran ◽

Fifit Juniarti ◽

Fery Azis Wijaya

Keyword(s):

Breast Cancer ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Cancer Cell Lines ◽

Andrographis Paniculata ◽

Normal Fibroblast ◽

Breast Cancer Cell Lines ◽

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Sambiloto (Andrographis paniculata) banyak digunakan untuk mengobati berbagai penyakit di Indonesia dan negara-negara Asia lainnya. Dalam studi ini, ekstrak metanol dan etanol sambiloto yang diperoleh dari B2PTO Tawangmangu telah diuji terhadap sel lini kanker payudara T47D dan MCF-7 dan sel lini normal fibroblast HFL-1 menggunakan reaksi enzimatik 3-(4,5-dimethylthiazoyl-2-yl) 2,5-diphenyltetrazoliumbromide (MTT). Uji in vitro terhadap sel lini normal fibroblast HFL-1 menunjukkan bahwa 50 ppm ekstrak metanol sambiloto tidak menghambat pertumbuhan sel. Tetapi, ekstrak metanol dan etanolnya menghasilkan IC50 yang relatif rendah pada sel lini kanker payudara, yaitu 111 ppm dan 122 ppm pada sel lini MCF-7 dan 70 ppm dan 197 ppm pada sel lini T47D. Selain itu, campuran ekstrak sambiloto yang mengandung 25% ekstrak Thyponium divaricatum dan Anredera cordifolia memberikan daya hambat pertumbuhan pada sel kanker payudara MCF-7 yang lebih besar, dengan nilai IC50 masing-masing adalah 68 ppm dan 34 ppm. Kesimpulannya, total ekstrak metanol atau etanol sambiloto yang diperoleh dari Tawangmangu memiliki potensi sebagai sumber senyawa anti-kanker serta perlu kajian lebih lanjut.Kata kunci: Ekstrak Andrographis paniculata, MTT, sel lini normal, sel lini kanker, aktivitas anti kanker ABSTRACTSambiloto (Andrographis paniculata) is widely used as medicine to treat various diseases in Indonesia and other Asian countries. In this study, methanolic and ethanolic extracts of sambiloto collected from B2PTO Tawangmangu have been tested againts breast cancer cell lines of T47D and MCF-7 and normal fibroblast cell line of HFL-1 using enzymatic reaction of 3-(4,5-dimethylthiazoyl-2-yl) 2,5-diphenyltetrazoliumbromide (MTT). In vitro assay performed on normal fibroblast of HFL-1 cell line showed that 50 ppm of methanolic extract of sambiloto did not inhibit cell growth. However, methanolic and ethanolic extracts of sambiloto gave relatively low of IC50 on breast cancer cell lines which were 111 ppm and 122 ppm on the MCF-7 cell lines and 70 ppm and 197 ppm on the T47D cell lines, respectively. In addition, the mixture of sambiloto extract containing 25% of Thyponium divaricatum and Anredera cordifolia extracts confered greater growth inhibition on breast cancer cell line of MCF-7, where IC50 values were 68 ppm and 34 ppm, respectively. In conclusion, the total methanolic or ethanolic extract of sambiloto collected from Tawangmangu has potency as a source of anti-cancer compounds and needs further study.Key words: Andrographis paniculata extract, MTT, normal cell line, cancer cell lines, anti-cancer activity

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The Effect of a Ferrocene Containing Camphor Sulfonamide DK-164 on Breast Cancer Cell Lines

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190724094334 ◽

2019 ◽

Vol 19 (15) ◽

pp. 1874-1886

Author(s):

Maria Schröder ◽

Shazie Yusein-Myashkova ◽

Maria Petrova ◽

Georgi Dobrikov ◽

Mariana Kamenova-Nacheva ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Breast Cancer Cell Lines ◽

Regulatory Pathways ◽

Cycle Arrest ◽

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Background: Drug resistance is a major cause of cancer treatment failure. Most cancer therapies involve multiple agents, to overcome it. Compounds that exhibit strong anti-tumor effect without damaging normal cells are more and more in the focus of research. Chemotherapeutic drugs, combining different moieties and functional groups in one molecule, can modulate different regulatory pathways in the cell and thus reach the higher efficacy than the agents, which affect only one cellular process. Methods: We tested the effect of recently synthesized ferrocene-containing camphor sulfonamide DK-164 on two breast cancer and one breast non-cancer cell lines. The cytotoxic effects were evaluated using the standard MTT-dye reduction and clonogenic assays. The apoptotic or autophagic effects were evaluated by Annexin v binding or LC3 puncta formation assays respectively. Cell cycle arrest was determined using flow cytometry. Western blot and immunofluorescent analyses were used to estimate the localization and cellular distribution of key regulatory factors NFκB and p53. Results: Compound DK-164 has well pronounced cytotoxicity greater to cancer cells (MDA-MB-231 and MCF-7) compared to non-cancerous (MCF-10A). IC50 of the substance caused a cell cycle arrest in G1 phase and induced apoptosis up to 24 hours in both tumor cells, although being more pronounced in MCF-7, a functional p53 cell line. Treatment with IC50 concentration of the compound provoked autophagy in both tumor lines but is better pronounced in the more aggressive cancer line (MDA-MB-231). Conclusion: The tested compound DK-164 showed promising properties as a potential therapeutic agent.

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Chenopodium AlbumPrevents Progression of Cell Growth and Enhances Cell Toxicity in Human Breast Cancer Cell Lines

Oxidative Medicine and Cellular Longevity ◽

10.4161/oxim.2.3.8837 ◽

2009 ◽

Vol 2 (3) ◽

pp. 160-165 ◽

Cited By ~ 12

Author(s):

Menka Khoobchandani ◽

B. K. Ojeswi ◽

Bhavna Sharma ◽

Man Mohan Srivastava

Keyword(s):

Breast Cancer ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Human Breast Cancer ◽

Human Breast Cancer Cell ◽

Breast Cancer Cell Lines ◽

Human Breast ◽

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The present study is aimed to investigate the effects ofChenopodium album(leaves) on the growth of estrogen dependent (MCF-7) and estrogen independent (MDA-MB-468) human breast cancer cell lines. The different solvent extracts (petroleum ether, ethyl acetate and methanol) were assessed for their cytotoxicity using TBE (Trypan blue exclusion) and MTT [3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium] bioassay. These cells were cultured in MEM (minimum essential medium) medium and incubated with the dilution series of extracts (10–100 mg/ml) in CO2incubator at 37°C for 24 h. Among the various extracts studied for two cell lines, methanolic extract ofC. album(leaves) exhibited maximum antibreast cancer activity having IC50(the concentration of an individual compound leading to 50% inhibition) value 27.31 mg/ml against MCF-7 cell line. Significant percent inhibition (94.06%) in the MeOH extract ofC. album(leaves) at 48 h of exposure and concentration 100 mg/ml (p < 0.05) against MCF-7 breast cancer cell line, indicates the presence of some structural moiety responsible for this observed antiproliferative effect. In vivo study and structural elucidation of its bioactive principle are in progress. Our findings highlight the potential of this plant for its possible clinical use to counteract malignancy development as antibreast cancer bioagent.

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Activation of Intrinsic Apoptosis and G1 Cell Cycle Arrest by a Triazole Precursor, N-(4-chlorophenyl)-2-(4-(3,4,5-trimethoxybenzyloxy)benzoyl)-hydrazinecarbothioamide in Breast Cancer Cell Line

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200318100051 ◽

2020 ◽

Vol 20 (9) ◽

pp. 1072-1086

Author(s):

Stephanie B. Arulnathan ◽

Kok H. Leong ◽

Azhar Ariffin ◽

Huda S. Kareem ◽

Kevin K.H. Cheah

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Cancer Cell Line ◽

Cycle Arrest ◽

Flow Cytometric ◽

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Background: Oxadiazoles, triazoles, and their respective precursors have been shown to exhibit various pharmacological properties, namely antitumour activities. Cytotoxic activity was reported for these compounds in various cancer cell lines. Aim and Objectives: In this study, we aim at investigating the mechanism of apoptosis by N-(4-chlorophenyl)-2-(4- (3,4,5-trimethoxybenzyloxy)benzoyl)-hydrazinecarbothioamide, a triazole precursor, henceforth termed compound P7a, in breast cancer cell line, MCF-7. We first screen a series of analogues containing (3,4,5-trimethoxybenzyloxy) phenyl moiety in breast cancer cell lines (MCF-7 and MDA-MB-231) to select the most cytotoxic compound and demonstrate a dose- and time-dependent cytotoxicity. Then, we unravel the mechanism of apoptosis of P7a in MCF-7 as well as its ability to cause cell cycle arrest. Methods: Synthesis was performed as previously described by Kareem and co-workers. Cytotoxicity of analogues containing (3,4,5-trimethoxybenzyloxy)phenyl moiety against MCF-7 and MDA-MB-231 cell lines was evaluated using the MTS assay. Flow cytometric analyses was done using Annexin V/PI staining, JC-1 staining and ROS assay. The activity of caspases using a chemoluminescence assay and western blot analysis was conducted to study the apoptotic pathway induced by the compound in MCF-7 cells. Lastly, cell cycle analysis was conducted using flow cytometry. Results: Upon 48 hours of treatment, compound P7a inhibited the proliferation of human breast cancer cells with IC50 values of 178.92 ± 12.51μM and 33.75 ± 1.20μM for MDA-MB-231 and MCF-7, respectively. Additionally, compound P7a showed selectivity towards the cancer cell line, MCF-7 compared to the normal breast cell line, hTERT-HME1, an advantage against current anticancer drugs (tamoxifen and vinblastine). Flow cytometric analyses using different assays indicated that compound P7a significantly increased the proportion of apoptotic cells, increased mitochondria membrane permeabilisation and caused generation of ROS in MCF-7. In addition, cell cycle analysis showed that cell proliferation was arrested at the G1 phase in the MCF-7 cell line. Furthermore, upon treatment, the MCF-7 cell line showed increased activity of caspase-3/7, and caspase-9. Lastly, the western blot analysis showed the up-regulation of pro-apoptotic proteins along with up-regulation of caspase-7 and caspase-9, indicating that an intrinsic pathway of apoptosis was induced. Conclusion: The results suggest that compound P7a could be a potential chemotherapeutic agent for breast cancer.

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miR-622 Induces Breast Cancer Cell MCF-7 Proliferation, Migration, and Invasion by Directly Negatively Targeting EYA1

Journal of Nanomaterials ◽

10.1155/2022/9000689 ◽

2022 ◽

Vol 2022 ◽

pp. 1-10

Author(s):

Pan Tang ◽

Yanyan Shen ◽

Jihui Yang ◽

Nan Wen ◽

Ying Liu ◽

...

Keyword(s):

Breast Cancer ◽

Cell Line ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Interaction Mechanism ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Breast Cancer Cell Lines ◽

Breast Cancer Patients ◽

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Breast cancer is the most common female cancer in the world. Breast cancer patients are currently treated with a combination of surgery, chemotherapy, radiotherapy, and targeted therapy, but the 5-year overall survival rate is still low. Therefore, we plan to explore the potential interaction mechanism between miR-622 and EYA1 in the breast cancer cells and their effect on proliferation, migration, and invasion of breast cancer, to lay a foundation for the gene therapy of breast cancer and improve the therapeutic effect. This study found that miR-622 was highly expressed in breast cancer cell lines, while EYA1 was poorly. In MCF-7 cell line, miR-622 had the highest expression level, while EYA1 had the lowest. Besides, the bioinformatics analysis showed that EYA1 possesses putative miR-622 binding sites within its 3 ′ UTR. The increased miR-622 significantly enhanced the proliferation, migration, and invasion of MCF-7 cell line and inhibited luciferase reporter activity in the 3 ′ UTR of EYA1-WT. When upregulating the expression of miR-622, the mRNA and protein expression levels of EYA1 were significantly decreased. We also found that the silencing of EYA1 promoted the proliferation, migration, and invasion of breast cancer MCF-7 cell line. These results indicate that miRNA-622 plays a tumor-promoting role in breast cancer through targeted negative regulation of EYA1, suggesting that miRNA-622 may become a potential target for breast cancer treatment.

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