Chlorogenic acid activates ERK1/2 and inhibits proliferation of osteosarcoma cells

Sapio, Luigi; Salzillo, Alessia; Illiano, Michela; Ragone, Angela; Spina, Annamaria; Chiosi, Emilio; Pacifico, Severina; Catauro, Michelina; Naviglio, Silvio

doi:10.1002/jcp.29269

Cited by 35 publications

(26 citation statements)

References 62 publications

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“…In accordance with our previous findings [23], Figure 1A shows a different responsiveness to CGA between U2OS and MG-63, the latter recognized as the least sensitive model. These discrepancies became quite obvious especially when OS cells were exposed to 200 and 400 µM CGA for 72 h. Indeed, whilst at these doses the inhibition index was 52% and 74% in U2OS, respectively, in MG-63, the losses were partially restrained, achieving values of 27% and 62%, correspondingly.…”

Section: Cga and Doxo Affect Cell Viability In Os Cells Differentlysupporting

confidence: 92%

“…We previously described that CGA strongly decreases the clonogenic potential of both U2OS and MG-63, whereas several findings report the Doxo ability to restrict colony formation in different cancer models, including OS [23,33].…”

Section: Co-administration Cga Plus Doxo Further Reduces the Clonogenic Potential In Os Cellsmentioning

confidence: 97%

“…In this connection, we lastly examined the CGA consequences in three different human OS cell lines, demonstrating that, albeit to a different extent, CGA inhibits growth and promotes cell death via apoptosis induction [23]. Moreover, CGA prevented Tyr705 Signal Transducer and Activator of Transcription 3 (STAT3) phosphorylation and triggered a remarkable Extracellular-signal-Regulated Kinase1/2 (ERK1/2) activation [23,24].…”

Section: Introductionmentioning

confidence: 99%

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Chlorogenic Acid Enhances Doxorubicin-Mediated Cytotoxic Effect in Osteosarcoma Cells

Salzillo

Ragone

Spina

et al. 2021

IJMS

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Despite the recurring outbreak of resistance mechanisms and adverse reactions, doxorubicin (Doxo) still remains the standard-of-care for several cancers, including osteosarcoma (OS). As an appealing source of phytochemical compounds, naturally occurring molecules have extensively been reported to overcome Doxo limitations in preclinical models. Unlike other dietary polyphenols, only few studies recognize chlorogenic acid (CGA) as a potential partner in combination therapy, while, conversely, its anticancer evidence is steadily growing, ultimately in OS. On this basis, herein we examine the cooperating effects between CGA and Doxo in U2OS and MG-63 human OS cells. With respect to Doxo alone, the concomitant administration of CGA further decreased cell viability and growth, promoting cell death potentially via apoptosis induction. Furthermore, a longer-lasting reduction in clonogenic potential deeply supported the CGA ability to improve Doxo efficacy in those cells. Remarkably, CGA treatment ameliorated Doxo-induced cytotoxicity in H9c2 rat cardiomyocyte cells instead. Although inactivation of p44/42 MAPK was detected in response to CGA plus Doxo, PD98059-mediated p44/42 MAPK impairment enhanced the combination outcome in OS cells. These findings firstly propose CGA as a promising chemosensitizer and cardioprotective agent in OS therapy, suggesting the p44/42 MAPK pathway as relevantly involved in CGA-mediated Doxo susceptibility.

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Section: Cga and Doxo Affect Cell Viability In Os Cells Differentlysupporting

confidence: 92%

Section: Co-administration Cga Plus Doxo Further Reduces the Clonogenic Potential In Os Cellsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Chlorogenic Acid Enhances Doxorubicin-Mediated Cytotoxic Effect in Osteosarcoma Cells

Salzillo

Ragone

Spina

et al. 2021

IJMS

Self Cite

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“…More and more novel anticancer agents from natural products have been used in osteosarcoma treatment. Sapio et al demonstrate that CGA acts as an anticancer molecule affecting the cell cycle and provoking cell growth inhibition mainly by apoptosis induction by ERK1/2 activation [ 32 ]. They also reported AdipoR affected osteosarcoma cell cycle and cell death in the mTORC1 pathway [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg5 Inhibits Human Osteosarcoma Cell Proliferation and Induces Cell Apoptosis through PI3K/Akt/mTORC1‐Related LC3 Autophagy Pathway

Liu

et al. 2021

Oxidative Medicine and Cellular Longevity

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The function and mechanism underlying the suppression of human osteosarcoma cells by ginsenoside-Rg5 (Rg5) was investigated in the present study. MG-63, HOS, and U2OS cell proliferation was determined by MTT assay after Rg5 treatment for 24 h. Rg5 inhibited human osteosarcoma cell proliferation effectively in a dose-dependent manner. The range of effective inhibitory concentrations was 160-1280 nM. Annexin V-FITC and PI double-staining assay revealed that Rg5 induced human osteosarcoma cell apoptosis. Western blotting, qRT-PCR, and FACS experiments revealed that Rg5 inhibited human osteosarcoma cells via caspase-3 activity which was related to the LC3-mediated autophagy pathway. Rg5 decreased the phosphorylation of PI3K, Akt, and mTORC1 activation. In contrast, LC3-mediated autophagy and caspase-3 activity increased significantly. A PI3K/AKT stimulator, IGF-1, reversed Rg5-induced cell autophagy and apoptosis in MG-63 cells. Collectively, the current study demonstrated that Rg5 induced human osteosarcoma cell apoptosis through the LC3-mediated autophagy pathway. Under physiological conditions, activation of PI3K/AKT/mTORC1 inhibits LC3 activity and caspase-3-related cell apoptosis. However, Rg5 activated LC3 activity by inhibiting the activation of PI3K/AKT/mTORC1. The present study indicated that Rg5 could be a promising candidate as a chemotherapeutic agent against human osteosarcoma.

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“…As a robust metastatic tumor in children and adolescents, osteosarcoma is highly invasive. 28 The poor clinical outcome of OS patients is a massive problem in clinical treatment. Therefore, it is necessary to find new molecular targets and study their potential mechanism of action.…”

Section: Discussionmentioning

confidence: 99%

<p>CircRNA Circ_0001721 Promotes the Progression of Osteosarcoma Through miR-372-3p/MAPK7 Axis</p>

Gao¹,

Ma²,

Gao³

et al. 2020

CMAR

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Background: Osteosarcoma (OS) is the most common bone tumor. Many studies have reported that circular RNAs (circRNAs) play an important role in the development of a variety of human cancers. However, the underlying mechanism of circ_0001721 in regulating osteosarcoma progression remains unknown. Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the levels of circ_0001721, miR-372-3p, and mitogen-activated protein kinase 7 (MAPK7) in osteosarcoma tissues and cells. Besides, glycolysis was investigated by glucose consumption, lactate production and hexokinase II (HK2) protein level. Cell proliferation and apoptosis were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry, separately. Cell migration and invasion were determined by transwell assay. Moreover, the protein levels of HK2 and epithelial-to-mesenchymal transition (EMT) markers were determined by Western blot analysis. The relationship between miR-372-3p and circ_0001721 or MAPK7 was predicated by starbase v3.0 and confirmed by dualluciferase reporter assay or RNA binding protein immunoprecipitation (RIP) assay. Murine xenograft model was established to investigate the role of circ_0001721 in vivo. Results: The levels of circ_0001721 and MAPK7 were upregulated in osteosarcoma tissues and cells, while miR-372-3p was downregulated. Knockdown of circ_0001721 inhibited glycolysis, cell proliferation, cell migration, invasion and epithelial-to-mesenchymal transition (EMT), and promoted apoptosis. Circ_0001721 was validated as a sponge of miR-372-3p and mediated glycolysis, cell proliferation, apoptosis, migration, invasion, and EMT of osteosarcoma cells through miR-372-3p. MAPK7 was a target of miR-372-3p and overexpression of MAPK7 attenuated anti-cancer role of miR-372-3p in OS cells. Further studies revealed that circ_0001721 regulates MAPK7 expression via sponging miR-372-3-p. Finally, knockdown of circ_0001721 inhibited tumor progression in vivo. Conclusion: Circ_0001721 promoted osteosarcoma development through the miR-372-3p/ MAPK7 axis.

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Chlorogenic acid activates ERK1/2 and inhibits proliferation of osteosarcoma cells

Cited by 35 publications

References 62 publications

Chlorogenic Acid Enhances Doxorubicin-Mediated Cytotoxic Effect in Osteosarcoma Cells

Chlorogenic Acid Enhances Doxorubicin-Mediated Cytotoxic Effect in Osteosarcoma Cells

Ginsenoside Rg5 Inhibits Human Osteosarcoma Cell Proliferation and Induces Cell Apoptosis through PI3K/Akt/mTORC1‐Related LC3 Autophagy Pathway

<p>CircRNA Circ_0001721 Promotes the Progression of Osteosarcoma Through miR-372-3p/MAPK7 Axis</p>

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