scholarly journals The Bcl-2 silencing with an Antisense Oligonucleotide: Increase early Apoptosis

2021 ◽  
Author(s):  
Mohsen Sedaghat Janaghard ◽  
Vahid Erfani-Moghadam ◽  
Ali Akbar Saffar Moghadam
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Cellular Proliferation ◽  
Molecular Therapy ◽  
Cellular Delivery ◽  
Breast Cancer Patients ◽  
Combination Drug ◽  
Early Apoptosis ◽  
Mcf 7

Abstract Background Breast cancer is a heterogenic disease and hormone dependence. Estrogen receptor is positive in more than seventy percent of breast cancer patients. Tamoxifen is an estrogen receptor (ER) antagonist and used as the first line of treatment. Drug resistance is a main reason in failure of cancer treatment and progression of the disease. Combination drug therapy is a method to treatment but is not sufficient. New approaches like molecular therapy reveal new insight to cancer therapy. Studies shown, Bcl-2 gene family inhibitors and ER blockers enhance recovery. Interfering molecules such as antisense can inhibit the expression of Bcl-2 and push the cancer cells to apoptosis. Nevertheless, their effectiveness is low, mostly due to their direct use. Methods Our team designed an Antisense Oligonucleotides (ASO). The MCF-7 and the MDA-MB-231breast cancer cell lines used to evaluate cellular proliferation. Liposome and cationic nano-complex (Niosome) used to increase cellular delivery of ASO and Tamoxifen. We also investigated the cytotoxicity and apoptotic effects of Tamoxifen, naked ASO and Nano-packed ASO. Results The ASO functional potency to assess apoptosis and expression of Bcl-2 mRNA compared in different groups. The results indicated, significant down regulation of Bcl-2 gene and inhibition of MCF-7 and MDA-MB-231 cellular proliferation. Flow-cytometry showed early apoptosis in all groups. Conclusions The ASO reduced the expression of Bcl-2 gene. It also had the synergistic effect with the Tamoxifen. In all studied groups, it was able to push cancer cells to apoptosis. The cationic nano-complex (Niosome) was more efficient than the liposome in delivering designed oligo antisense Bcl-2 into the cancer cells.

scholarly journals Hesperidin and Chlorogenic Acid Synergistically Inhibit the Growth of Breast Cancer Cells via Estrogen Receptor/Mitochondrial Pathway

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 950
Author(s):  
Pang-Hung Hsu ◽  
Wei-Hsuan Chen ◽  
Chen JuanLu ◽  
Shu-Chen Hsieh ◽  
Shih-Chao Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Chlorogenic Acid ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Breast Cancer Patients ◽  
Atp Production ◽  
Chemotherapy Drugs ◽  
Mitochondrial Functions ◽  
Mcf 7

Breast cancer is the most common cancer in women worldwide. Hesperidin (Hes) and chlorogenic acid (CA) are traditional medicinal molecules that abundantly exist in natural plants or foods. These compounds have been shown to prevent and suppress various cancers and therefore can be utilized as adjunctive therapies to aid cancer treatment. Here, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays show a greater synergistic inhibitory effect on the growth of breast cancer cells, MCF-7, but not normal breast cells, MCF-10A, than hesperidin or chlorogenic acid alone. We present the possible molecular signaling pathways in MCF-7 cells with or without herbal molecule treatments via proteomic approaches. The data were further analyzed by Ingenuity Pathway Analysis (IPA) and confirmed by quantifying mRNA associated with the estrogen-receptor signaling pathway and mitochondrial functions. We demonstrated that the expression of CYC1, TFAM, ATP5PB, mtATP6, mtDNA, and NRF-1 were decreased upon 12 h treatment, and subsequent ATP production was also significantly decreased at 24 h. These results identified a synergistic effect induced by combinational treatment with hesperidin and chlorogenic acid, which can regulate mitochondria and ATP production through the estrogen receptor pathway in MCF-7 cells. However, none of the treatments induced the generation of reactive oxygen species (ROS), suggesting that ROS likely plays no role in the observed pharmacological activities. Overall, our study sheds light on the adequacy of hesperidin and chlorogenic acid to serve as an adjunctive therapy when co-administrated with chemotherapy drugs in breast cancer patients.

scholarly journals ERβ-induced MFN2 inhibits the migration and invasiveness of breast cancer cells by inhibiting the P-AKT signaling pathway

2020 ◽  
Author(s):  
Mengyu Wei ◽  
Jun Hao ◽  
Xiaomei Liao ◽  
Yinfeng Liu ◽  
Ruihuan Fu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Akt Pathway ◽  
Cancer Cell Migration ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
Mcf 7

Abstract Background Mitofusin 2 (MFN2) is localized on the outer membrane of mitochondria and is closely related to the migration of malignant tumor cells. Estrogen receptor β (ERβ) plays an anticancer role in breast cancer. Our previous experiments showed that ERβ can induce MFN2 expression, which then inhibits breast cancer cell migration. However, the exact mechanism by which ERβ-induced MFN2 inhibits breast cancer cell migration is unknown. Methods In this study, immunohistochemistry was first used to detect the expression of MFN2 in breast cancer tissues, and its relationship with the clinicopathological characteristics and prognosis of breast cancer patients was analyzed. MCF-7 and MDA-MB-231 cells were transfected with ERβ and MFN2 knockdown or expression plasmids. Western blot was used to detect the effects of ERβ on MFN2 and MFN2 on P-AKT473 and MMP2; the P-AKT pathway inhibitor LY294002 was administered to cells transfected with MFN2 knockdown plasmids, Western blot, immunocytofluorescence, and a wound healing assay revealed the effect of MFN2 on its downstream signaling pathway and the migration of breast cancer cells. Results This study found that the expression of MFN2 is related to the molecular type and prognosis of breast cancer patients ( P <0.05). The positive expression rate of MFN2 in triple-negative breast cancer was significantly lower than that in the HER2 + and luminal types. However, MFN2 expression was unrelated to age, tumor size, lymph node metastasis, TNM stage, histological type and grade ( P >0.05); ERβ positively regulated MFN2 expression and reduced the migration of both MCF-7 and MDA-MB-231 cells, while MFN2 knockdown increased the expression of P-AKT473 and MMP2. In contrast, the overexpression of MFN2 inhibited the expression of P-AKT473 and MMP2. These results showed that in MFN2 knockdown cells treated with LY294002, P-AKT473 and MMP2 expression levels were reversed. The reversal of P-AKT473 and MMP2 expression levels inhibits the invasiveness of human breast cancer cells. Conclusion MFN2 is related to the molecular subtype and prognosis of breast cancer. In human breast cancer MCF-7 and MDA-MB-231 cells, ERβ-induced MFN2 can inhibit the P-AKT pathway, which inhibits the invasiveness and migration of both breast cancer cell lines.

scholarly journals The Role of Aryl Hydrocarbon Receptor and Crosstalk with Estrogen Receptor in Response of Breast Cancer Cells to the Novel Antitumor Agents Benzothiazoles and Aminoflavone

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Mariana A. Callero ◽  
Andrea I. Loaiza-Pérez
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Aryl Hydrocarbon Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Antitumor Agents ◽  
Breast Cancers ◽  
Nude Mouse Model ◽  
Aryl Hydrocarbon ◽  
Mcf 7

Many estrogen-receptor- (ER-) expressing breast cancers become refractory to ER-based therapies. New antitumor drugs like aminoflavone (AF) and benzothiazoles (Bzs) have been developed and have exquisite antitumor activity in ER+MCF-7 and T47D cells and in a MCF-7 nude mouse model. ER(−) breast cancer cells like MDA-MB-231 are less susceptible. We previously found in MCF-7 cells that these drugs activate the aryl hydrocarbon receptor (AhR) via translocation to the nucleus, induction of AhR-specific DNA binding activity, and expression of CYP1A1, whose transcription is controlled by the AhR-ARNT transcription factor. CYP1A1 metabolizes AF and Bz to a species which directly or after further metabolism damages DNA. In contrast an AhR-deficient variant of MCF-7 or cells with predominantly nuclear AhR expression, such as MDA-MB 231, are resistant. Thus, these drugs, unlike other neoplastic agents, require AhR-mediated signaling to cause DNA damage. This is a new treatment strategy for breast cancers with intact AhR signaling.

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