F1012-2 Induced ROS-Mediated DNA Damage Response through Activation of MAPK Pathway in Triple-Negative Breast Cancer

Dai, Lingjie; Tian, Shasha; Zhang, Jinyao; Lu, Mengyuan; Zhu, Jun; Zhao, Huajun

doi:10.1155/2021/6650045

Cited by 11 publications

(9 citation statements)

References 31 publications

(29 reference statements)

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“…Together with DNA damage, response factors including tumor suppressor p53 and NF-κB become activated [24]. We previously reported that F1012-2 induced DNA damage in TNBC [14]. In the present study, F1012-2 not only regulated the expression of p53, but also significantly decreased the expression levels of NF-κB family members p-p65 and p105 and had no effect on the expression of p65 and p50.…”

Section: Discussionsupporting

confidence: 46%

“…Western blotting was carried out as described previously [14,16]. Cells were seeded on 6-well culture dishes (8×10 5 cells/dish) and treated with the indicated concentrations of F1012-2 for 24 h. Cells were harvested, washed twice with ice-cold PBS, lysed by incubation in RIPA buffer for 30 min on ice, and then centrifuged at 16100 ×g at 4°C for 15 min.…”

Section: Western Blotting Analysismentioning

confidence: 99%

“…F1012-2 is a sesquiterpene lactone isolated from the Chinese herbal medicine Eupatorium lindleyanum DC. Previously we found that F1012-2 exhibited a significant anticancer effect and induced cell cycle arrest, apoptosis and ROS-mediated DNA damage [14]. To elucidate the mechanism of F1012-2 action, we further investigated its effect on the crosstalk between p53 and NF-κB signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

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Eupatorium lindleyanum DC. sesquiterpene fraction F1012-2 regulates p53/NF-κB signaling pathways in human breast cancer

Wang

Tao

et al. 2022

ARCH BIOL SCI BELGRA

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F1012-2, a novel sesquiterpene lactone isolated from the Chinese herbal medicine Eupatorium lindleyanum DC, exhibits an antitumor effect. In this study, we investigated the anticancer activities of F1012-2 on ten human breast cancer lines and demonstrated significantly lower IC50 values for triple-negative breast cancer (TNBC) than for non-TNBC cell lines. The transcription factors p53 and nuclear factor-?B (NF-?B) are important regulators of tumorigenesis. F1012-2 not only depleted mutant p53, but also activated wild-type p53. F1012-2 reduced the expression of phosphorylated p65 and p105 F-?B family members and coregulated p53, NF-?B members and their dependent targets. To further clarify the key role of p53, lentivirus small hairpin RNA (shRNA) infection was used to knockdown p53 in MDAMB- 231 cells. F1012-2 significantly reduced the inhibitory effect on cell proliferation and apoptosis, while the levels of p53, NF-?B family members and their dependent genes were not significantly different. F1012-2 exhibited a significant antitumor effect and reduced the expression of p53 in MDA-MB-231 xenografts. Taken together, our results show that F1012-2 exhibited an inhibitory effect on TNBC and affected the regulation of p53/NF-?B signaling pathways.

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Section: Discussionsupporting

confidence: 46%

Section: Western Blotting Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Eupatorium lindleyanum DC. sesquiterpene fraction F1012-2 regulates p53/NF-κB signaling pathways in human breast cancer

Wang

Tao

et al. 2022

ARCH BIOL SCI BELGRA

Self Cite

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“…Besides, it is reported that the elevated ROS can inhibit Bcl-2 expression and activate Bax expression in the mitochondria [ 42 ]. F1012-2, another compound isolated from Eupatorium lindleyanum DC., has been reported to cause DNA damage in TNBC cells by increasing ROS production [ 43 ]. In this study, the generation of ROS was notably elevated in TNBC cells upon exposure to EO.…”

Section: Discussionmentioning

confidence: 99%

Eupalinolide O Induces Apoptosis in Human Triple-Negative Breast Cancer Cells via Modulating ROS Generation and Akt/p38 MAPK Signaling Pathway

Zhao

Chen

et al. 2022

Journal of Oncology

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Background. Triple-negative breast cancer (TNBC) is a subtype of breast cancer with limited therapeutic options. Eupalinolide O (EO) was reported to inhibit tumor growth. This study is aimed at exploring the role of EO on TNBC both in vivo and in vitro. Methods. In in vitro experiments, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenic assay were conducted to measure the impact of EO on TNBC cell growth at different concentrations and time points. Flow cytometry was conducted to evaluate cell apoptosis. Mitochondrial membrane potential (MMP) loss, caspase-3 activity, and reactive oxygen species (ROS) generation were assessed. The expressions of apoptosis-related mRNAs and Akt/p38 MAPK signaling pathway-related proteins were measured. In in vivo experiments, by injecting TNBC cells into the nude mice to induce xenograft tumor, mice were treated with EO for 20 days. Then, in vivo bioluminescence imaging system was utilized to monitor the growth and distribution of TNBC cells. Tumor volume and weight were also recorded. Hematoxylin-eosin (HE) staining and ELISA assay were applied to observe tumor tissue morphology and ROS levels. Furthermore, western blotting was conducted to observe the expression of apoptosis-related proteins and Akt/p38 MAPK signaling pathway-associated proteins. Results. EO inhibited the cell viability and proliferation of TNBC cells but not normal epithelial cells. Furthermore, EO induced apoptosis, decreased MMP, and elevated caspase-3 activity and ROS content in TNBC cells. Meanwhile, the expression of apoptosis-related mRNAs and Akt/p38 MAPK pathway-related proteins was regulated by EO treatment. Besides, in vivo experiments demonstrated EO not only suppressed tumor growth, Ki67 expression, ROS generation, and Akt phosphorylation but also upregulated caspase-3 expression and p-38 phosphorylation. Conclusion. EO may induce cell apoptosis in TNBC via regulating ROS generation and Akt/p38 MAPK pathway, indicating EO may be a candidate drug for TNBC.

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“…HER2+ breast cancer usually grows aggressively, and HER2-targeted antibody therapy using pertuzumab/trastuzumab plus a taxane has been widely used as the first-line standard therapy in HER2-enriched BC patients [5]. TNBC accounts for 15-20% of all breast cancers; it is considered to be one of the most drug-resistant cancer types and is characterized by a high malignancy [6]. Due to the absence of molecular targets, no desirable targeted therapeutic agents have been clinically approved for TNBC, so the mortality rate remains high [7,8].…”

Section: Introductionmentioning

confidence: 99%

Integrated Molecular Characterization to Reveal the Association between Kynurenine 3-Monooxygenase Expression and Tumorigenesis in Human Breast Cancers

Tsang

Liao

et al. 2021

JPM

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Kynurenine 3-monooxygenase (KMO) is overexpressed in several tumors and participates in the progression of breast cancer tumorigenesis, including cancer types such as triple-negative breast cancer (TNBC). This malignant gene is an enzyme in the kynurenine pathway, which is involved in the carcinogenesis of cancer through immune function manipulation. However, it remains unclear whether the role of the KMO contributes to tumorigenesis and immune functions in human breast cancer. In this study, we found that KMO was highly expressed in different types of tumors, especially in invasive ductal breast carcinoma. In addition, KMO expression was positively correlated with the malignant clinical features of patients with breast cancer, such as TNBC and a nodal-positive status, along with patients with a higher Nottingham prognostic index (NPI). Furthermore, the top ten KMO-correlated genes were the chemokines and pro-inflammatory cytokines known to be involved in the progression of various cancers, therefore, KMO may facilitate breast cancers via synergistically regulating inflammatory responses in tumors with these hub genes. Taken together, these findings highlight the tumor-promotion role of KMO in breast cancers and suggest that KMO can serve as a biomarker for prognosis prediction in breast cancer patients.

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F1012-2 Induced ROS-Mediated DNA Damage Response through Activation of MAPK Pathway in Triple-Negative Breast Cancer

Cited by 11 publications

References 31 publications

Eupatorium lindleyanum DC. sesquiterpene fraction F1012-2 regulates p53/NF-κB signaling pathways in human breast cancer

Eupatorium lindleyanum DC. sesquiterpene fraction F1012-2 regulates p53/NF-κB signaling pathways in human breast cancer

Eupalinolide O Induces Apoptosis in Human Triple-Negative Breast Cancer Cells via Modulating ROS Generation and Akt/p38 MAPK Signaling Pathway

Integrated Molecular Characterization to Reveal the Association between Kynurenine 3-Monooxygenase Expression and Tumorigenesis in Human Breast Cancers

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