Inhibitory Effects of Osthole on Human Breast Cancer Cell Progression via Induction of Cell Cycle Arrest, Mitochondrial Dysfunction, and ER Stress

Park, Wonhyoung; Song, Gwonhwa; Lim, Whasun

doi:10.3390/nu11112777

Cited by 33 publications

(31 citation statements)

References 66 publications

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“…Novel Target of OST. An increasing number of studies revealed that OST acted as an inhibitory role in the oncogenesis and development of BrCa [7][8][9]; there is still a lack of systematic research on its molecular mechanisms. To obtain a comprehensive insight into its molecular mechanisms, we use the "limma" R package to extract DEGs between the control and the treatment group.…”

Section: Systematic Bioinformatics Analysis Reveals Gng7 As Amentioning

confidence: 99%

“…OST has been shown to significantly inhibit the growth and metastasis of BrCa, thus serving as an effective candidate drug for the comprehensive treatment of BrCa [ 7 , 8 ]. Although several studies have revealed the molecular mechanisms of OST in the treatment of BrCa [ 9 ], there is still a lack of systematic research on its molecular mechanism.…”

Section: Introductionmentioning

confidence: 99%

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Osthole Inhibits Breast Cancer Progression through Upregulating Tumor Suppressor GNG7

Mei

Wang

Zhao

et al. 2021

Journal of Oncology

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Osthole (OST) is a plant-derived compound that can inhibit the proliferation of tumor cells and has a tumor-suppressive effect in multiple types of cancers. However, the mechanisms of OST-mediated breast cancer (BrCa) inhibition were still largely unknown. In this study, we made full use of the GSE85871 dataset to identify potential targets of OST in BrCa via multiple bioinformatics analysis. Next, a series of in vitro experiments were conducted to check the role of GNG7 in BrCa and the relationship between OST and GNG7. Through a series of bioinformatics analyses, GNG7 was identified as a potential target of OST, which could be significant upregulated by OST exposure in BrCa cells. Besides, GNG7 was lowly expressed in BrCa tissues compared with normal breast tissues, and BrCa patients with low GNG7 expression had shorter overall survival (OS) and relapse-free survival (RFS) compared with those with high GNG7 expression. Moreover, GNG7 silencing significantly enhanced cell proliferation and inhibited apoptosis, and exogenous overexpression of GNG7 showed reverse effects on BrCa cells. Last but not least, GNG7 inhibition could notably rescue OST-mediated cytotoxic effects. In summary, we identified GNG7 as a novel target for OST in BrCa and a potential tumor suppressor. Thus, OST could be therapeutically beneficial for BrCa through a GNG7-dependent mechanism.

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Section: Systematic Bioinformatics Analysis Reveals Gng7 As Amentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Osthole Inhibits Breast Cancer Progression through Upregulating Tumor Suppressor GNG7

Mei

Wang

Zhao

et al. 2021

Journal of Oncology

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“…Because the expression of CDK inhibitors in these cells may be insufficient, the G 1 phase of the cell cycle arrest provides cells with a repair mechanism or follows the pathological changes ( 27 ). Therefore, targeting the cell-cycle disorders have been considered promising targets for cancer treatment ( 28 ). Results from flow cytometry showed that cells in the G 0 /G 1 phase increased and those in the S phase decreased in Eupafolin-treated cells.…”

Section: Discussionmentioning

confidence: 99%

Eupafolin inhibits breast cancer cell proliferation and induces apoptosis by inhibiting the PI3K/Akt/mTOR pathway

et al. 2021

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Eupafolin is a flavonoid extracted from common sage. Previous studies have reported that Eupafolin has antioxidant, anti-inflammatory, and anti-tumor effects. However, its role in breast cancer remains unclear. The present study investigated the effects and underlying mechanism of action of Eupafolin using breast cancer cell lines. The effects of Eupafolin on breast cancer cell proliferation, migration, apoptosis and the cell cycle were determined. Cell viability and Transwell assays, reverse transcription-quantitative PCR, flow cytometry and western blot analysis were used in this study. The data showed that the proliferation, migration and invasion ability of EO771 cells treated with Eupafolin was significantly decreased, and the apoptosis rate was increased compared with that of the control. The protein levels of Bax and cleaved caspase 3 increased, whereas that of Bcl-2 decreased. In addition, Eupafolin treatment also caused the proliferation of breast cancer cells to be arrested at the G 0 /G 1 phase. Furthermore, results from western blotting indicated that Eupafolin treatment decreased the protein levels of p-PI3K, p-Akt and p-mTOR. Taken together, the present findings demonstrate that Eupafolin has a significant inhibitory effect on the proliferation of EO771 cells, inhibits cell migration and invasion, and promotes cell apoptosis, thereby causing G 0 /G 1 phase arrest, at least partially through the PI3K/Akt/mTOR signaling pathway. Therefore, the findings provide novel insights regarding the use of Eupafolin for the treatment of breast cancer.

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“…It has been reported that osthole-induced antitumor effects is relevant to ROS overproduction [26]. Although different forms of PCDs have different molecular mechanisms, it seems that they cannot bypass the key link of ROS generation [12].…”

Section: Discussionmentioning

confidence: 99%

Osthole Induces Apoptosis, Secondary Necrosis and Mitophagy Via NQO1-Mediated ROS Overproduction in HeLa Cells

Huangfu¹,

Wang²,

Yu³

et al. 2020

Preprint

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Background: Osthole is a natural coumarin which has been proved to inhibit growth of cancer cells by inducing cancer cells death, while its mechanism of anticancer remains unclearly. In our study, we found that osthole activated multiple forms of cell death including apoptosis, secondary necrosis and mitophagy in receptor interacting protein kinase (RIP) 3-deficient cervical cancer HeLa cells. Methods: Cell viability was detected by MTT assay. Cell membrane integrity was detected by LDH release assay and PI staining. Cell apoptosis and necrosis were detected by flow cytometry assay. Reactive oxygen species (ROS) was detected by DCFH-DA staining and mitochondrial membrane potential (MMP) was detected by JC-1 staining using flow cytometry. The expression of proteins was detected by western blotting assay and proteomics. Xenograft tumor model was used to evaluate the effect of osthole in vivo.Results: Our study showed osthole caused HeLa cells apoptosis and secondary necrosis, which is a phenomenon of the apoptotic cells’ plasma membrane breakdown. And when Hela cells pretreatment with Z-DEVD-FMK, an irreversible caspase-3 inhibitor, not only inhibited osthole-induced apoptosis but also necrosis. Moreover, we found that Z-DEVD-FMK reversed the effect of osthole on the induction of cleaved the N-terminal fragment of GSDME in Hela cells. Furthermore, inhibition of NAD (P) H: quinone oxidoreductase 1 (NQO1) by osthole induced the overproduction of reactive oxygen species (ROS). ROS inhibitor N-Acetyl-L-cysteine (NAC) not only reduced osthole-induced apoptosis, but also reversed its effect on the necrotic induction and the GSDME N-terminal generation. It was shown that osthole decreased mitochondrial membrane potential (MMP) and increased the expression of PTEN-induced putative kinase 1 (PINK1) and Parkin, which indicated that the activation of mitophagy induced by osthole. Meanwhile, as well as apoptosis and secondary necrosis, mitophagy was also restrained by NAC. Conclusions: In conclusion, all these data suggested that osthole induced apoptosis, secondary necrosis and mitophagy via NQO1-mediated ROS overproduction.

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Inhibitory Effects of Osthole on Human Breast Cancer Cell Progression via Induction of Cell Cycle Arrest, Mitochondrial Dysfunction, and ER Stress

Cited by 33 publications

References 66 publications

Osthole Inhibits Breast Cancer Progression through Upregulating Tumor Suppressor GNG7

Osthole Inhibits Breast Cancer Progression through Upregulating Tumor Suppressor GNG7

Eupafolin inhibits breast cancer cell proliferation and induces apoptosis by inhibiting the PI3K/Akt/mTOR pathway

Osthole Induces Apoptosis, Secondary Necrosis and Mitophagy Via NQO1-Mediated ROS Overproduction in HeLa Cells

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