scholarly journals Anticancer Effects and Molecular Action of 7-α-Hydroxyfrullanolide in G2/M-Phase Arrest and Apoptosis in Triple Negative Breast Cancer Cells

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 407
Author(s):  
Siriphorn Chimplee ◽  
Sittiruk Roytrakul ◽  
Suchada Sukrong ◽  
Theera Srisawat ◽  
Potchanapond Graidist ◽  
...  

Triple negative breast cancer (TNBC) is a breast cancer subtype characterized by the absence of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 expression. TNBC cells respond poorly to targeted chemotherapies currently in use and the mortality rate of TNBC remains high. Therefore, it is necessary to identify new chemotherapeutic agents for TNBC. In this study, the anti-cancer effects of 7-α-hydroxyfrullanolide (7HF), derived from Grangea maderaspatana, on MCF-7, MDA-MB-231 and MDA-MB-468 breast cancer cells were assessed using MTT assay. The mode of action of 7HF in TNBC cells treated with 6, 12 and 24 µM of 7HF was determined by flow cytometry and propidium iodide (PI) staining for cell cycle analysis and annexin V/fluorescein isothiocyanate + PI staining for detecting apoptosis. The molecular mechanism of action of 7HF in TNBC cells was investigated by evaluating protein expression using proteomic techniques and western blotting. Subsequently, 7HF exhibited the strongest anti-TNBC activity toward MDA-MB-468 cells and a concomitantly weak toxicity toward normal breast cells. The molecular mechanism of action of low-dose 7HF in TNBC cells primarily involved G2/M-phase arrest through upregulation of the expression of Bub3, cyclin B1, phosphorylated Cdk1 (Tyr 15) and p53-independent p21. Contrastingly, the upregulation of PP2A-A subunit expression may have modulated the suppression of various cell survival proteins such as p-Akt (Ser 473), FoxO3a and β-catenin. The concurrent apoptotic effect of 7HF on the treated cells was mediated via both intrinsic and extrinsic modes through the upregulation of Bax and active cleaved caspase-7–9 expression and downregulation of Bcl-2 and full-length caspase-7–9 expression. Notably, the proteomic approach revealed the upregulation of the expression of pivotal protein clusters associated with G1/S-phase arrest, G2/M-phase transition and apoptosis. Thus, 7HF exhibits promising anti-TNBC activity and at a low dose, it modulates signal transduction associated with G2/M-phase arrest and apoptosis.

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Elisa Martino ◽  
Daniela Cristina Vuoso ◽  
Stefania D’Angelo ◽  
Luigi Mele ◽  
Nunzia D’Onofrio ◽  
...  

Abstract Polyphenols represent the most studied class of nutraceuticals that can be therapeutics for a large spectrum of diseases, including cancer. In this study, we investigated for the first time the antitumor activities of polyphenol extract from Annurca apple (APE) in MDA-MB-231 triple negative breast cancer cells, and we explored the underlying mechanisms. APE selectively inhibited MDA-MB-231 cell viability and caused G2/M phase arrest associated with p27 and phospho-cdc25C upregulation and with p21 downregulation. APE promoted reactive oxygen species (ROS) generation in MDA-MB-231 cells while it acted as antioxidant in non-tumorigenic MCF10A cells. We demonstrated that ROS generation represented the primary step of APE antitumor activity as pretreatment with antioxidant N-acetylcysteine (NAC) prevented APE-induced G2/M phase arrest, apoptosis, and autophagy. APE downregulated Dusp-1 and induced a significant increase in JNK/c-Jun phosphorylation that were both prevented by NAC. Moreover, downregulation of JNK by its specific inhibitor SP600125 significantly diminished the anticancer activity of APE indicating that ROS generation and sustained JNK activation represented the main underlying mechanism of APE-induced cell death. APE also inhibited AKT activation and downregulated several oncoproteins, such as NF-kB, c-myc, and β-catenin. In light of these results, APE may be an attractive candidate for drug development against triple negative breast cancer.


PLoS ONE ◽  
2014 ◽  
Vol 9 (7) ◽  
pp. e103760 ◽  
Author(s):  
Yanjie Kong ◽  
Jianchao Chen ◽  
Zhongmei Zhou ◽  
Houjun Xia ◽  
Ming-Hua Qiu ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
pp. 73-83
Author(s):  
Mrudul Pravinbhai Vekaria ◽  
Pravin Tirgar

Therapeutics against breast cancer is a major research field, due to inefficiency or partial efficiency of existing therapeutics.  An urge to discover better therapeutics always persists. Our objective is to study salicin against breast cancer cells, in order to find its therapeutic properties. To study the effect of salicin on breast cancer cells, we performed MTT assay on MCF-7 (hormone positive) and MDA-MB-231 (triple negative) breast cancer cell lines, we did brine shrimp lethality test (BSLT) assay to see the lethal effects of salicin. By the help of bioinformatics we tried to locate the targets that delineate salicin activity. Salicin was docked with estrogen receptor (ER), progesterone receptor (PR) and Human epidermal growth factor receptor 2 (HER2) to study its binding efficiency and possible targets of salicin. Salicin remarkably reduces cell viability both in MCF-7 and MDA-MB-231, along with being lethal to brine shrimps. These results together opine that salicin can be an effective therapeutics against breast cancer cells. The mechanism of action of salicin is probably through ER, PR and HER2 receptors because it can efficiently bind these receptors with minimum energy required for binding. This explains that salicin can easily bind to these receptors. These results together opine that salicin can be an effective therapeutics against breast cancer cells. The mechanism of action of salicin is probably through ER, PR and HER2 receptors because it can efficiently bind these receptors with minimum binding energy. ER, PR and HER2 are major reasons behind the disease pathogenicity depending on the type of breast cancer. According to our results salicin may either induce apoptosis or reduce cellular mitosis both via P53 dependent and independent pathway, which makes salicin a good choice of both hormone positive and negative breast cancer cells. 


2020 ◽  
Vol Volume 13 ◽  
pp. 4089-4097 ◽  
Author(s):  
Yang Wang ◽  
Nan Wu ◽  
Jun Zhang ◽  
Huidong Wang ◽  
Xiaojuan Men

2017 ◽  
Vol 12 (1) ◽  
pp. 221-229
Author(s):  
Abeer M. Ashmawy ◽  
Mona A. Sheta ◽  
Faten Zahran ◽  
Abdel Hady A. Abdel Wahab

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