Chlorogenic acid inhibits osteosarcoma carcinogenesis via suppressing the STAT3/Snail pathway

Zhang, Fang; Yin, Guodong; Han, Xiufu; Jiang, Xin-qiang; Bao, Zhongsheng

doi:10.1002/jcb.28318

Cited by 26 publications

(20 citation statements)

References 30 publications

(60 reference statements)

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“…Our findings indicate that CGA inhibits cell viability, cell growth, and colony-forming ability in all osteosarcoma cell lines tested, with a different sensitivity among them (U2OS and MG-63 the most and the least sensitive, respectively). Notably, our data are fully in agreement with a very recent study in which CGA exerts antiproliferative effects in p53-deficient OS cells Saos-2 and MG-63 (F. Zhang, Yin, Han, Jiang, & Bao, 2018). Herein, we confirm and extend such data, providing the first evidence regarding CGA and p53-proficient U2OS cells.…”

Section: Discussionsupporting

confidence: 92%

“…In contrast to ERK1/2 tendency, CGA induces a significant downregulation of STAT3 phosphorylation after 48 hr of treatment, whereas no obvious variations have been detected in the STAT3 total protein levels. Importantly, these findings are in line with a very recent paper in which the importance of STAT3 in CGA-produced outcome is described (F. Zhang et al, 2018). In particular, they show that CGA downregulates phospho-STAT3 in MG-63 and Saos-2 cells and that the activation of the STAT3/Snail pathway reverts the effects of CGA on OS cell growth and apoptosis.…”

Section: Discussionsupporting

confidence: 90%

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

Sapio

Salzillo

Illiano

et al. 2019

Journal Cellular Physiology

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Osteosarcoma (OS) is a very aggressive metastatic pediatric and adolescent tumor. Due to its recurrent development of chemotherapy resistance, clinical outcome for OS patients remains poor. Therefore, discovering more effective anticancer agents is needed. Chlorogenic acid (CGA) is a phenolic compound contained in plant-related products that modulates many cellular functions and inhibits cell proliferation in several cancer types. However, few evidence is available in OS. Here, we investigate the effects of CGA in U2OS, Saos-2, and MG-63 OS cells. By multiple approaches, we demonstrate that CGA acts as anticancer molecule affecting the cell cycle and provoking cell growth inhibition mainly by apoptosis induction. We also provide evidence that CGA strongly activates extracellular-signal-regulated kinase1/2 (ERK1/2). Strikingly, ERK1/2 inhibitor PD98059 sensitizes the cells to CGA. Altogether, our data enforce the evidence of the anticancer activity mediated by CGA and provide the rationale for the development of innovative therapeutic strategies in OS cure.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 90%

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

Sapio

Salzillo

Illiano

et al. 2019

Journal Cellular Physiology

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“…Matrix metallopeptidases (MMPs) are known to play important roles in breast cancer metastasis. A wellstudied mechanism of STAT3-mediated cell metastasis is through upregulating MMP2, MMP9, Twist, Snail, Slug and vimentin [47][48][49]. Ma et al have reported that inhibition of STAT3 phosphorylation could reduce the expression of vasodilator-stimulated phosphoprotein (VASP), MMP2 and MMP9 in breast cancer [50].…”

Section: The Role Of Stat3 In Breast Cancer Metastasismentioning

confidence: 99%

Role of STAT3 signaling pathway in breast cancer

2020

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Breast cancer has grown to be the second leading cause of cancer-related deaths in women. Only a few treatment options are available for breast cancer due to the widespread occurrence of chemoresistance, which emphasizes the need to discover and develop new methods to treat this disease. Signal transducer and activator of transcription 3 (STAT3) is an early tumor diagnostic marker and is known to promote breast cancer malignancy. Recent clinical and preclinical data indicate the involvement of overexpressed and constitutively activated STAT3 in the progression, proliferation, metastasis and chemoresistance of breast cancer. Moreover, new pathways comprised of upstream regulators and downstream targets of STAT3 have been discovered. In addition, small molecule inhibitors targeting STAT3 activation have been found to be efficient for therapeutic treatment of breast cancer. This systematic review discusses the advances in the discovery of the STAT3 pathways and drugs targeting STAT3 in breast cancer.

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“…Since both compounds have been reported to induce cell death in OS, we speculated that combination treatment CGA plus Doxo could enhance single-agent cytotoxicity [23,24,34]. To address this hypothesis, we firstly discriminated living from dead cells using Trypan Blue as the exclusion dye.…”

Section: Cga Enhances Doxo-mediated Cytotoxic Effects In Os Cellsmentioning

confidence: 99%

“…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%

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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Chlorogenic acid inhibits osteosarcoma carcinogenesis via suppressing the STAT3/Snail pathway

Abstract: Chlorogenic acid (CA) is a polyphenol compound that possesses anticancer

Cited by 26 publications

References 30 publications

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

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

Role of STAT3 signaling pathway in breast cancer

Chlorogenic Acid Enhances Doxorubicin-Mediated Cytotoxic Effect in Osteosarcoma Cells

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