Saussurea lappaClarke-Derived Costunolide Prevents TNFα-Induced Breast Cancer Cell Migration and Invasion by Inhibiting NF-κB Activity

Choi, Youn Kyung; Cho, Sung Gook; Woo, Sang‐Mi; Yun, Yee Jin; Jo, J.H.; Kim, Wooyoung; Shin, Yong Cheol; Ko, Seong‐Gyu

doi:10.1155/2013/936257

Cited by 41 publications

(37 citation statements)

References 41 publications

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“…Recent studies suggest that the NF-κB pathway may be related to tumor metastasis [28][29][30] and chemotherapy resistance [31][32][33]. The migration and invasion of thyroid cancer cells [30], breast cancer cells [28], and oral squamous cancer cells [29] are related to the activation of the NF-κB pathway.…”

Section: Discussionmentioning

confidence: 99%

Galectin-3 regulates metastatic capabilities and chemotherapy sensitivity in epithelial ovarian carcinoma via NF-κB pathway

Liu

Wang

et al. 2016

Tumor Biol.

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Galectin-3 (Gal-3) has been found to be involved in the tumor progression and chemoresistance of epithelial ovarian cancer (EOC). Some studies have shown that Gal-3 may interact with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). However, it is unclear whether the effects of Gal-3 on the metastasis and chemosensitivity of EOC are related to NF-κB. In this study, we aimed to explore whether Gal-3 promoted progression and carboplatin resistance in EOC via NF-κB pathway. Plasmid transfection and RNA interference were used to upregulate or downregulate the expression of Gal-3 in ovarian cancer cell lines. Then, the expression of Gal-3 and the protein expressions of phosphorylation NF-κB pathway molecules were further detected by Western blot. Transwell migration assay was employed to detect the effects of Gal-3 on the migration and invasion of ovarian cancer cell lines. After treatment with carboplatin, flow cytometry (FCM) was employed to detect the effects of Gal-3 on carboplatin-induced apoptosis. Immunofluorescence technique was used to examine the translocation of phosphorylated P65 into the nucleus in ovarian cancer cells after the upregulation of Gal-3. After the knockdown of Gal-3 by small interfering RNA (siRNA), the migration and the invasion of cancer cells were significantly inhibited while the apoptosis and the sensitivities to carboplatin increased. Western blot showed reduction in the phosphorylation components of the NF-κB pathway: inhibitor of kappa B (IκB), IκB kinase (IKK), and P65. However, after the Gal-3 upregulation by plasmid transfection, the capabilities of migration and invasion of cancer cells were significantly promoted while the apoptosis and the sensitivities to carboplatin decreased. Immunofluorescence showed increased nuclear translocation of P65. Inhibitors of the NF-κB pathway did not affect the Gal-3 expression level in ovarian cancer cells. Gal-3 may affect the migratory and invasive capabilities of cancer cells as well as the chemosensitiviy to carboplatin in EOC by acting through the NF-κB pathway.

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Section: Discussionmentioning

confidence: 99%

Galectin-3 regulates metastatic capabilities and chemotherapy sensitivity in epithelial ovarian carcinoma via NF-κB pathway

Liu

Wang

et al. 2016

Tumor Biol.

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“…Sesquiterpene lactones are phytochemicals derived from Chinese medicinal herbs, and have been demonstrated previously to have anti-neoplastic and anti-inflammatory activities (8). Costunolide is a well-known sesquiterpene lactone and a number of previous studies have shown that it has a broad spectrum of cytotoxicity against human cancer cell lines of different origins (6,18,(20)(21)(22)26,27).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, costunolide potentiates 1,25-(OH)2D3-induced differentiation in HL-60 promyelocytic leukemia cells by modulating NF-κB activation (16,17). Previous studies have demonstrated that costunolide has anti-tumor potential by inhibiting proliferation, inducing apoptosis and reducing invasion and metastasis in a number of tumor cells including intestinal neoplasia and melanoma, leukemia and hepatocellular carcinoma cells, and cervical, prostate, bladder, colon and breast cancer cells (6,(18)(19)(20)(21)(22)(23)(24)(25). The effects of costunolide on human lung squamous carcinoma cells are still unknown.…”

Section: Introductionmentioning

confidence: 99%

Costunolide induces G1/S phase arrest and activates mitochondrial-mediated apoptotic pathways in SK-MES 1 human lung squamous carcinoma cells

Hua

Zhang

et al. 2016

Oncology Letters

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Abstract. Despite the availability of several therapeutic options, a safer and more effective modality strategy is required for the treatment of lung cancer. Costunolide, a sesquiterpene lactone which isolated from the Saussurea lappa, has potent anticancer properties. In the present study, the effects of costunolide on cell viability, the cell cycle and apoptosis in SK-MES-1 human lung squamous carcinoma cells were investigated. Costunolide induced morphological changes and inhibited growth of SK-MES-1 cells growth. Flow cytometric analysis data demonstrated that costunolide significantly induced apoptosis of SK-MES-1 cells and induced cell cycle arrest at G1/S phase in a dose-dependent manner. Through upregulation in the expression of p53 and Bax, and downregulation in the expression of Bcl-2 and activation of caspase-3, costunolide-induced apoptosis was confirmed by western blot analysis. In addition, the significant loss of mitochondrial membrane potential indicated that costunolide may induce apoptosis via the mitochondria-dependent pathway in SK-MES-1 cells. These results highlight the potential effects of costunolide as an anti-cancer agent in a human lung squamous carcinoma cell line.

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“…Costunolide, a sesquiterpene lactone isolated from Inula helenium (Compositae) [1,2], has previously been shown to counteract inflammation [3][4][5], gastric ulcer [6], tumor growth [3,[7][8][9][10][11], metastasis [12,13], angiogenesis [3], osteoclast differentiation [14], and fibrosis [3]. Costunolide is in part effective by decreasing vascular endothelial growth factor (VEGF) [3], interleukin (IL)-1β, IL-6, IL-17 [3], tumor necrosis factor (TNF)-α [3] and transforming growth factor (TGF-β) [3].…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand costunolide protects against oxidative stress [25]. Signaling involved in the effects of Costulonide includes stimulation of mitogen-activated kinases [20,26] as well as inhibition of the transcription factor NFκB [10,13,15] and the Wnt/β-Catenin Pathway [9]. The stimulation of apoptosis further involves mitochondria [19,27].…”

Section: Introductionmentioning

confidence: 99%

Stimulation of Eryptosis, the Suicidal Erythrocyte Death, by Costunolide

Fink

Bhuyan

Zacharopoulou

et al. 2018

Cell Physiol Biochem

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Background/Aims: The sesquiterpene lactone Costunolide is effective against various disorders including inflammation and malignancy. The substance is effective in part by triggering suicidal death or apoptosis of tumor cells. Mechanisms involved include altered function of transcription factors and mitochondria. Erythrocytes lack nuclei and mitochondria but are – in analogy to apoptosis of nucleated cells – able to enter suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca²⁺ activity ([Ca²⁺]_i), oxidative stress and ceramide. The present study explored, whether Costunolide induces eryptosis and, if so, to shed light on the mechanisms involved. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, [Ca²⁺]_i from Fluo3-fluorescence, reactive oxygen species (ROS) formation from 2’,7’-dichlorodihydrofluorescein (DCF)-dependent fluorescence, and ceramide abundance utilizing specific antibodies. Results: A 48 hours exposure of human erythrocytes to Costunolide (15 µg/ml) significantly enhanced the percentage of annexin-V-binding cells, significantly decreased forward scatter and significantly increased Fluo3-fluorescence, DCF-fluorescence, and ceramide abundance. The effect of Costunolide on annexin-V-binding was significantly blunted by removal of extracellular Ca²⁺. Conclusion: Costunolide triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect at least in part due to Ca²⁺ entry and paralleled by oxidative stress and ceramide formation.

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Saussurea lappaClarke-Derived Costunolide Prevents TNFα-Induced Breast Cancer Cell Migration and Invasion by Inhibiting NF-κB Activity

Cited by 41 publications

References 41 publications

Galectin-3 regulates metastatic capabilities and chemotherapy sensitivity in epithelial ovarian carcinoma via NF-κB pathway

Galectin-3 regulates metastatic capabilities and chemotherapy sensitivity in epithelial ovarian carcinoma via NF-κB pathway

Costunolide induces G1/S phase arrest and activates mitochondrial-mediated apoptotic pathways in SK-MES 1 human lung squamous carcinoma cells

Stimulation of Eryptosis, the Suicidal Erythrocyte Death, by Costunolide

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