Resveratrol eliminates cancer stem cells of osteosarcoma by STAT3 pathway inhibition

Peng, Lihua; Jiang, Dianming

doi:10.1371/journal.pone.0205918

Cited by 73 publications

(54 citation statements)

References 39 publications

(37 reference statements)

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“…Here, our results revealed that BD exhibited the capacity to inhibit the stem cell like traits of osteosarcoma cells and inhibit OSCs self‐renewal ability. Previous studies have reported that STAT3 activation was important in maintaining CSCs, and inhibition of STAT3 signaling may be involved in CSCs stemness attenuation . Consistent with these findings, we found that BD could deactivate STAT3 signaling and inhibition of STAT3 using Stattic significantly suppressed the sphere‐forming and self‐renewal capacity of osteosarcoma cells.…”

Section: Discussionsupporting

confidence: 90%

“…The data showed that BD stimulation reduced β ‐catenin expression in MNNG/HOS cells (Figure I). It has been reported that STAT3 signaling repression was implicated in resveratrol induced elimination of OSCs . Our results consistently showed that inhibition of STAT3 signaling using Stattic, significantly inhibits sphere formation and self‐renewal ability of OSCs (Figure B,D,F).…”

Section: Resultssupporting

confidence: 84%

“…Previous studies have reported that STAT3 activation was important in maintaining CSCs, and inhibition of STAT3 signaling may be involved in CSCs stemness attenuation. 33,50,51 Consistent with these findings, we found that BD could deactivate STAT3 signaling and inhibition of STAT3 using Stattic significantly suppressed the sphere-forming and self-renewal capacity of osteosarcoma cells. Collectively, our data indicated that inhibitory effects of BD on OSC stemness may be through the suppression of STAT3 signaling, and BD could be a promising agent for OSC-targeted therapy.…”

Section: Discussionsupporting

confidence: 85%

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Bruceine D inhibits tumor growth and stem cell‐like traits of osteosarcoma through inhibition of STAT3 signaling pathway

Wang

Zhong

et al. 2019

Cancer Medicine

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Patients with osteosarcoma exhibiting resistance to chemotherapy or presenting with metastasis usually have a poor prognosis. Osteosarcoma stem cells (OSCs) are a potential cause of tumor metastasis, relapse, and chemotherapy resistance. Therefore, it is necessary to develop novel therapeutic drugs, which not only kill osteosarcoma cells but also target OSCs. This study aims to explore the anti‐osteosarcoma effects of Bruceine D (BD), a natural compound derived from Brucea javanica, and investigate its underlying mechanisms. Results demonstrated that BD could significantly inhibit cell proliferation and migration, induce cell cycle arrest, and promote apoptosis in osteosarcoma cells. Besides, BD could also suppress the sphere‐forming and self‐renewal ability of OSCs. Mechanistically, the inhibitory role of BD on osteosarcoma cell growth and migration including OSC stemness was partially executed through the inhibition of STAT3 signaling pathway. More importantly, BD showed significant anti‐osteosarcoma activity without obvious side effects in vivo. Collectively, the results of this study demonstrated that BD exerts a strong inhibitory effect on tumor growth and stem cell like traits of osteosarcoma which may be partially due to STAT3 inhibition, suggesting that BD maybe a promising therapeutic candidate against osteosarcoma.

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Section: Discussionsupporting

confidence: 90%

Section: Resultssupporting

confidence: 84%

Section: Discussionsupporting

confidence: 85%

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Bruceine D inhibits tumor growth and stem cell‐like traits of osteosarcoma through inhibition of STAT3 signaling pathway

Wang

Zhong

et al. 2019

Cancer Medicine

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“…Moreover, treating gastric cancer cells with resveratrol elevated the levels of pro-apoptotic proteins such as Bax, while the levels of anti-apoptotic proteins such as Bcl-2 were decreased compared to untreated controls . Treatment of osteosarcoma cells with 20 μM resveratrol results in reduction of cell viability, decrease in self-renewing and tumorigenesis via inhibition of intracellular STAT3 signaling and cytokine synthesis (Peng & Jiang, 2018). In general, the anti-cancer activity of resveratrol is based on the suppression of the expression of proteins involved in carcinogenesis, such as phospholipid scramblase 1 , stimulation of caspase 3 cleavage (Lucas et al, 2018) and activation of the mitochondrial ROS signaling pathway (Zheng et al, 2018).…”

Section: Anti-cancer Activitymentioning

confidence: 99%

Health benefits of resveratrol administration

Aebisher²,

2019

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Resveratrol is a polyphenol which is abundant in grape skin and seeds. Sources of resveratrol in food also include wine, berries, and peanuts. This compound displays many properties including activity against glycation, oxidative stress, inflammation, neurodegeneration, several types of cancer, as well as aging. Due to the fact that resveratrol is generally well-tolerated, it is believed to be a promising compound in preventing many diseases such as diabetes and associated complications. Unfortunately, this compound exhibits low bioavailability and solubility. The aim of this review is to summarize recent information from in vitro and in vivo studies on animals and humans on the multiple effects of resveratrol on health and benefits of its intake.

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“…It has been proposed that a common gene expression program underpins both cancer and stemness. Consistent with this hypothesis, it has been shown that STAT3 is required to maintain stemness in many different tumors [34,35,[64][65][66][67][68][69][70][71][72][73][74][75][76][77]. At least in breast cancer, a critical mechanism stimulated by STAT3 to regulate stemness involves genes in fatty acid oxidation [72,73] and the ability of STAT3 to adjust the ROS levels produced in mitochondria [73].…”

Section: Reprogramming and Stemnessmentioning

confidence: 89%

STAT3 and STAT5 Activation in Solid Cancers

Igelmann¹,

Neubauer²,

Ferbeyre³

2019

Preprint

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The Signal Transducer and Activator of Transcription (STAT)3 and 5 are activated by many cytokine receptors to regulate specific gene expression and mitochondrial functions. Their role in cancer is largely context dependent as they can both act as oncogenes and tumor suppressors. We review here the role of STAT3/5 activation in solid cancers and summarize their association to survival in cancer patients. The molecular mechanisms that underpins the oncogenic activity of STAT3/5 signaling includes the regulation of genes that control cell cycle, cell death, inflammation and stemness. In addition, STAT3 mitochondrial functions are required for transformation. On the other hand, several tumor suppressor pathways act on or are activated by STAT3/5 signaling including the p19ARF/p53 pathway, tyrosine phosphatases, suppressor of cytokine signaling 1 and 3, the sumo ligase PIAS3, the E3 ubiquitin ligase TMF/ARA160 and the miRNAs miR-124 and miR-1181. Cancer mutations and epigenetic alterations may alter the balance between prooncogenic and tumor suppressor activities associated to STAT3/5 signaling explaining their context dependent association to tumor progression both in human cancers and animal models.

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Resveratrol eliminates cancer stem cells of osteosarcoma by STAT3 pathway inhibition

Cited by 73 publications

References 39 publications

Bruceine D inhibits tumor growth and stem cell‐like traits of osteosarcoma through inhibition of STAT3 signaling pathway

Bruceine D inhibits tumor growth and stem cell‐like traits of osteosarcoma through inhibition of STAT3 signaling pathway

Health benefits of resveratrol administration

STAT3 and STAT5 Activation in Solid Cancers

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