scholarly journals Circadian Rhythms and Breast Cancer: The Role of Per2 in Doxorubicin-Induced Cell Death

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Megan I. Mitchell ◽  
Anna-Mart Engelbrecht

Mammalian circadian rhythms form an integral physiological system allowing for the synchronisation of all metabolic processes to daily light/dark cycles, thereby optimising their efficacy. Circadian disruptions have been implicated in the onset and progression of various cancers, including those arising in the breast. Several links between the circadian protein Per2 and DNA damage responses exist. Aberrant Per2 expression results in potent downstream effects on both cell cycle and apoptotic targets, suggestive of a tumour suppressive role for Per2. Due to the severe dose limiting side effects associated with current chemotherapeutic strategies, including the use of doxorubicin, a need for more effective adjuvant therapies to increase cancer cell susceptibility has arisen. This study was therefore aimed at characterizing the role of Per2 in normal breast epithelia (MCF-12A) and in ER−breast cancer cells (MDA-MB-231) and also at determining the role of Per2 in doxorubicin-induced cell death. In both cell lines Per2 protein expression displayed a 24-hour circadian rhythm in both cell lines. Per2 was located predominantly in the cytoplasm, with nuclear localization observed with lower cytoplasmic fluorescent intensities. Our results show that Per2 silencing effectively sensitizes the chemoresistant MDA-MB-231 breast cancer cells to the cytotoxic effects of doxorubicin.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tiantian Tang ◽  
Guiying Wang ◽  
Sihua Liu ◽  
Zhaoxue Zhang ◽  
Chen Liu ◽  
...  

AbstractThe role of organic anion transporting polypeptide 1B3 (SLCO1B3) in breast cancer is still controversial. The clinical immunohistochemical results showed that a greater proportion of patients with negative lymph nodes, AJCC stage I, and histological grade 1 (P < 0.05) was positively correlated with stronger expression of SLCO1B3, and DFS and OS were also increased significantly in these patients (P = 0.041, P = 0.001). Further subgroup analysis showed that DFS and OS were significantly enhanced with the increased expression of SLCO1B3 in the ER positive subgroup. The cellular function assay showed that the ability of cell proliferation, migration and invasion was significantly enhanced after knockdown of SLCO1B3 expression in breast cancer cell lines. In contrast, the ability of cell proliferation, migration and invasion was significantly reduced after overexpress the SLCO1B3 in breast cancer cell lines (P < 0.05). Overexpression or knockdown of SLCO1B3 had no effect on the apoptotic ability of breast cancer cells. High level of SLCO1B3 expression can inhibit the proliferation, invasion and migration of breast cancer cells, leading to better prognosis of patients. The role of SLCO1B3 in breast cancer may be related to estrogen. SLCO1B3 will become a potential biomarker for breast cancer diagnosis and prognosis assessment.


Acta Naturae ◽  
2015 ◽  
Vol 7 (3) ◽  
pp. 133-139 ◽  
Author(s):  
A. M. Scherbakov ◽  
O. E. Andreeva

Phytoestrogens are a group of plant-derived compounds with an estrogen-like activity. In mammalians, phytoestrogens bind to the estrogen receptor (ER) and participate in the regulation of cell growth and gene transcription. There are several reports of the cytotoxic effects of phytoestrogens in different cancer cell lines. The aim of this study was to measure the phytoestrogen activity against breast cancer cells with different levels of ER expression and to elucidate the molecular pathways regulated by the leader compound. Methods used in the study include immunoblotting, transfection with a luciferase reporter vector, and a MTT test. We demonstrated the absence of a significant difference between ER+ and ER- breast cancer cell lines in their response to cytotoxic stimuli: treatment with high doses of phytoestrogens (apigenin, genistein, quercetin, naringenin) had the same efficiency in ER-positive and ER-negative cells. Incubation of breast cancer cells with apigenin revealed the highest cytotoxicity of this compound; on the contrary, naringenin treatment resulted in a low cytotoxic activity. It was shown that high doses of apigenin (50 М) do not display estrogen-like activity and can suppress ER activation by 17-estradiol. Cultivation of HER2-positive breast cancer SKBR3 cells in the presence of apigenin resulted in a decrease in HER2/neu expression, accompanied by cleavage of an apoptosis substrate PARP. Therefore, the cytotoxic effects of phytoestrogens are not associated with the steroid receptors of breast cancer cells. Apigenin was found to be the most effective phytoestrogen that strongly inhibits the growth of breast cancer cells, including HER2-positive ones.


2021 ◽  
Vol 7 (2) ◽  
Author(s):  
Mahtab Zarchini ◽  
Haleh Forouhandeh ◽  
Elham Safarzadeh ◽  
Omoleila Molavi ◽  
Vahideh Tarhriz ◽  
...  

Objective: The genus Anthriscus from the Umbelliferae family has valuable compounds and pharmacological properties. Terpenoids, phenolics, anthocyanins, podophyllotoxins, and others have been identified in Anthriscus genus which has effects like analgesic, antiviral, anti-inflammatory, hepatoprotective, and anti-platelet aggregation. The present study concerns the cytotoxic activity of A. nemorosa different extracts on breast cancer cells  (MCF-7) and normal cell lines (HFFF). Methods: Different extracts of aerial parts of  A. nemorosa were prepared using Soxhlet apparatus. The cytotoxicity of samples was assessed by MTT assay on breast cancer cells (MCF-7) and noncancerous cells (HFFF) with different concentrations of extracts in 24 and 48 hours. The most potent extract was fractioned and cytotoxic activity of fractions was considered, As well. A flow cytometry (annexin V/PI) assay has been used for detecting the mechanism of cell death in sample treated cell lines. Moreover, for clarifying volatile components of n-Hexane extract and its 80% and 100% VLC fractions were subjected to GC-MS apparatus. Results: Results indicated that n-Hexane extract and its 80% and 100% VLC fractions exhibited a significant (p<0.001) inhibitory effect on the growth of the MCF-7 cell line compared to the control group. Meanwhile, flow cytometry analysis revealed that potent extract caused cell death through necrosis and 80% and 100% fractions showed different mechanisms (such as autophagy). The major compounds, which maybe were in charge of showing cytotoxic activity were non-terpenoids. Conclusion: This study provides the evidence that in vitro cytotoxic activity of n-Hexane extract and 80% and 100% VLC fractions of A. nemorosa inhibited the proliferation of breast cancer cells (MCF7) via a different mechanism.


2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Stéphane Zingue ◽  
Abel Joël Gbaweng Yaya ◽  
Julia Cisilotto ◽  
Larissa Vanelle Kenmogne ◽  
Emmanuel Talla ◽  
...  

Abyssinone V-4′ methyl ether (AVME) isolated from Erythrina droogmansiana was recently reported to exhibit anti-mammary tumor effect in mice. The present work was therefore aimed at elucidating its cellular and molecular mechanisms. To achieve our goal, the cytotoxicity of AVME against tumoral and non-tumoral cell lines was evaluated by resazurin reduction test; flow cytometry allowed us to evaluate the cell cycle and mechanisms of cell death; the mitochondrial transmembrane potential, reactive oxygen species (ROS) levels, and caspase activities as well as apoptosis-regulatory proteins (Bcl-2 and Bcl-XL) were measured in MDA-MB-231 cells. Further, the antimetastatic potential of AVME was evaluated by invasion assay. AVME exhibited cytotoxic effects in all tested tumor cell lines and induced a significant increase in the percentage of MDA-MB-231 cells at G2/M and S phases of the cell cycle in a concentration-dependent manner. AVME also induced apoptosis in MDA-MB-231 cells, which was accompanied by the activation of caspase-3 and caspase-9 and downregulation of Bcl-2 and Bcl-XL proteins. Moreover, AVME suppressed cancer cell invasion by the inhibition of the metalloproteinase-9 activity. Findings from this study suggest that AVME has anti-breast cancer activities expressed through mitochondrial proapoptotic pathway including impairment of aggressive behaviors of breast cancer cells.


2005 ◽  
Vol 4 (9) ◽  
pp. 1006-1013 ◽  
Author(s):  
Yi Huang ◽  
Allison Pledgie ◽  
Ethel Rubin ◽  
Laurence J. Marton ◽  
Patrick M. Woster ◽  
...  

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