Design, Synthesis and Molecular Modeling of Quinoline Based Derivatives as Anti‐Breast Cancer Agents Targeting EGFR/AKT Signaling Pathway

Objective. To explore the ability of asiatic acid to interfere with the invasion and proliferation of breast cancer cells by inhibiting WAVE3 expression and activation through the PI3K/AKT signaling pathway. Methods. The MDA-MB-231 cells with strong invasiveness were screened by transwell assay, and plasmids with high expression of WAVE3 were constructed for transfection. The transfection effect and protein expression level of plasmids were verified by PCR and WB. The effects of asiatic acid on cell proliferation and invasion were investigated by flow cytometry. The xenografted tumor models in nude mice were established to study the antitumor activity of asiatic acid. Results. Asiatic acid significantly inhibited the activity of MDA-MB-231 cells, and the expression level of WAVE3 increased significantly in the tissue of ductal carcinoma in situ and was lower than that in the metastasis group. After plasmid transfection, the mRNA and protein expression of WAVE3 increased significantly in the cells. Asiatic acid at different concentrations had an impact on cell apoptosis and invasion and could significantly inhibit the expression of WAVE3, P53, p-PI3K, p-AKT, and other proteins. The T/C(%) of asiatic acid (50 mg/kg) for MDA-MB-231(F10) xenografted tumor in nude mice was 46.33%, with a tumor inhibition rate of 59.55%. Asiatic acid could significantly inhibit the growth of MDA-MB-231 (F10) xenografted tumors in nude mice (p<0.05). Conclusions. Asiatic acid interferes with the ability of breast cancer cells to invade and proliferate by inhibiting WAVE3 expression and activation and the mechanism of action may be related to the PI3K/AKT signaling pathway.

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Overexpression of IL-8 promotes cell migration via PI3K-Akt signaling pathway and EMT in triple-negative breast cancer

Pathology - Research and Practice ◽

10.1016/j.prp.2020.152902 ◽

2020 ◽

Vol 216 (4) ◽

pp. 152902 ◽

Cited By ~ 1

Author(s):

Fang Deng ◽

Yaguang Weng ◽

Xian Li ◽

Teng Wang ◽

Mengtian Fan ◽

...

Keyword(s):

Breast Cancer ◽

Cell Migration ◽

Signaling Pathway ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Akt Signaling ◽

Akt Signaling Pathway

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Role of regulatory miRNAs of the PI3K/AKT signaling pathway in the pathogenesis of breast cancer

Gene ◽

10.1016/j.gene.2020.144459 ◽

2020 ◽

Vol 737 ◽

pp. 144459 ◽

Cited By ~ 9

Author(s):

Farzad Rahmani ◽

Gordon A Ferns ◽

Sahar Talebian ◽

Mahnaz Nourbakhsh ◽

Amir Avan ◽

...

Keyword(s):

Breast Cancer ◽

Signaling Pathway ◽

Akt Signaling ◽

Akt Signaling Pathway

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Thidiazuron suppresses breast cancer progression via targeting miR-132 and miR-202-5p/PTEN axis mediated dysregulation of PI3K/AKT signaling pathway

Biochemistry and Cell Biology ◽

10.1139/bcb-2020-0377 ◽

2020 ◽

Author(s):

Hairul-Islam Ibrahim ◽

Mohammad Bani Ismail ◽

Rebai Ben Ammar ◽

Emad Ahmed

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Cancer Progression ◽

Cancer Metastasis ◽

Metastatic Cancer ◽

Akt Signaling ◽

Breast Cancer Metastasis ◽

Akt Signaling Pathway ◽

Stressful Environment

Chemo-resistance and metastatic disease development are the most common causes of breast cancer recurrence and death. Thidiazuron (TDZ) is a plant growth regulator, its biological role on human and animals has not been yet clarified. In the present study, we investigated the anticancer activity of this plant phytohormone on the drug resistant-triple negative breast cancer MDA-MB-231 cell line. Treatment of the breast cancer cells with TDZ (1-50 μM) caused more stressful environment and induced a significant increase in percentages of active caspases positive cells. In addition, TDZ treatment (5 and 10 μM) significantly attenuated the migration and the invasion activities of these highly metastatic cancer cells. Mechanistically, TDZ reducesd cancer progression and invasive activity through targeting miR-202-5p, which stimulatesd the expression of the phosphatase and tensin homolog (PTEN), the tumor suppressor that downregulates PI3K/AKT signaling pathway. In the meantime, TDZ treatment statistically upregulatesd the suppressor of breast cancer proliferation, miRNA-132 that is also implicated in dysregulating the TEN-AKT/the nuclear factor NFκB signaling pathway. Interestingly, our molecular docking analysis revealed potential non-covalent interaction between TDZ with AKT, PTEN and PI3K. These findings suggest that TDZ may suppresses breast cancer metastasis through targeting miRNA-132, miR-202-5p/PTEN and PI3K/AKT downstream molecules.

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