Quercetin induces apoptosis in the methotrexate-resistant osteosarcoma cell line U2-OS/MTX300 via mitochondrial dysfunction and dephosphorylation of Akt

Xie, Xianbiao; Yin, Juan Juan; Jia, Qiang; Wang, Jin; Zou, Changye; Brewer, Kari J.; Colombo, Chiara; Wang, Yaofei; Huang, Gang; Shen, Jingnan

doi:10.3892/or.2011.1328

Cited by 13 publications

(13 citation statements)

References 24 publications

(46 reference statements)

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“…Leukemic cells treated with Qu showed upregulation of BAX and increased phosphorylation of BCL-2 [52]. Similar results were observed in osteosarcoma [44] and breast cancer cells [46]. (iii) Qu induces the expression of death receptor- (DR-) 5, enhancing TNF-related apoptosis-inducing ligand- (TRAIL-) induced apoptosis [53–55] either by accumulating death receptors in lipid rafts [56] or inhibiting survivin in the ERK signalling pathway [57].…”

Section: Dietary Polyphenolssupporting

confidence: 59%

“…While, H 2 O 2 is eliminated by peroxidase, semiquinone and Qu radicals alter intracellular ROS metabolism by depleting the intracellular GSH pool in a concentration-dependent manner [39–41] and inhibiting thioredoxin reductase activity [42]. In vitro and in vivo studies (Table 1) show that Qu promotes ROS-induced apoptosis, necrosis, and autophagy [43] at a range of 10-100 μ M in a variety of cancers, including glioma [43], osteosarcoma [44], and cervical [45] and breast cancer [46]. Qu induces apoptosis through distinct mechanisms: (i) via the mitochondrial pathway through activation of caspase-3.…”

Section: Dietary Polyphenolsmentioning

confidence: 99%

See 1 more Smart Citation

ROS-Mediated Cancer Cell Killing through Dietary Phytochemicals

NavaneethaKrishnan

Rosales

Lee

2019

Oxidative Medicine and Cellular Longevity

148

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Reactive oxygen species (ROS) promote carcinogenesis by inducing genetic mutations, activating oncogenes, and raising oxidative stress, which all influence cell proliferation, survival, and apoptosis. Cancer cells display redox imbalance due to increased ROS level compared to normal cells. This unique feature in cancer cells may, therefore, be exploited for targeted therapy. Over the past few decades, natural compounds have attracted attention as potential cancer therapies because of their ability to maintain cellular redox homeostasis with minimal toxicity. Preclinical studies show that bioactive dietary polyphenols exert antitumor effects by inducing ROS-mediated cytotoxicity in cancer cells. These bioactive compounds also regulate cell proliferation, survival, and apoptotic and antiapoptotic signalling pathways. In this review, we discuss (i) how ROS is generated and (ii) regulated and (iii) the cell signalling pathways affected by ROS. We also discuss (iv) the various dietary phytochemicals that have been implicated to have cancer therapeutic effects through their ROS-related functions.

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Section: Dietary Polyphenolssupporting

confidence: 59%

Section: Dietary Polyphenolsmentioning

confidence: 99%

ROS-Mediated Cancer Cell Killing through Dietary Phytochemicals

NavaneethaKrishnan

Rosales

Lee

2019

Oxidative Medicine and Cellular Longevity

148

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“…PI3K/Akt pathway is a classical pathway modulating cisplatin resistance, thus influencing cisplatin resistance in osteosarcoma ( Zhao et al, 2013 ). Through mitochondrial dysfunction and dephosphorylation of Akt, quercetin induces apoptosis in methotrexate-resistant osteosarcoma cancer cells ( Xie et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Quercetin Enhances Cisplatin Sensitivity of Human Osteosarcoma Cells by Modulating microRNA-217-KRAS Axis

Zhang¹,

Guo²,

Chen³

et al. 2015

Molecules and Cells

114

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Quercetin can suppress osteosarcoma cell growth and metastasis. However, other effects of quercetin on osteosarcoma remain largely unknown. This research aims to evaluate the effects of quercetin in combination with cisplatin as treatment for osteosarcoma and investigate its regulatory mechanism. Cell viability and apoptosis in 143B cell line were determined after treatment with quercetin and/or cisplatin. RT-PCR and Western blot analysis were performed to determine the RNA or protein expression levels. Moreover, transwell assay was used to evaluate metastasis. Furthermore, rescue experiments were performed to investigate the potential regulatory mechanism of the treatment. Results showed that quercetin with concentration that was equal to or greater than 10 μM inhibited 143B proliferation, while 5 μM quercetin enhanced the cisplatin sensitivity of 143B cells. Expression of miR-217 was upregulated after quercetin and/or cisplatin treatment, while its target KRAS was downregulated both at mRNA and protein levels. MiR-217 knockdown led to the loss of enhanced cisplatin sensitivity while miR-217 overexpression showed the opposite effects, indicating that quercetin regulated cisplatin sensitivity by modulating the miR-217-KRAS axis. In conclusion, 5 μM quercetin enhanced the cisplatin sensitivity by modulating the miR-217-KRAS axis. This finding suggests that quercetin may be administered with cisplatin to improve the treatment for osteosarcoma.

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“…Based on this evidence, it is suggested that quercetin-induced apoptosis may be mediated by the mitochondrial-dependent pathway [ 93 ]. Another study has demonstrated that quercetin suppresses the viability of methotrexate (MTX)-resistant osteosarcoma cell line U2OS/MTX300 cells in a dose-dependent manner [ 94 ]. As evidenced by fluorescence staining and flow cytometry, quercetin induces apoptosis in the MTX-resistant cells, paralleled by a decrease in the potential of mitochondrial membrane, caspase-3 activation, mitochondrial cytochrome c release, Bax upregulation, and downregulation of p-Bad and Bcl-2.…”

Section: Quercetin and Osteosarcomamentioning

confidence: 99%

“…Active Akt plays a protective role against the Akt dephosphorylation, Bad, and degradation of poly(ADP-ribose) polymerase (PARP). Whereas, the combination of quercetin with LY294002 promotes the Bad and Akt dephosphorylation and cleavage of PARP [ 94 ]. The same result is concluded in a study by Yin et al [ 95 ].…”

Section: Quercetin and Osteosarcomamentioning

confidence: 99%

Anti-cancer properties of quercetin in osteosarcoma

et al. 2021

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Osteosarcoma is a primary bone tumor. Although it is a rare disease in general, it is the most common primary bone tumor among children. Despite the significant advances made in the field of osteosarcoma treatment, the outcomes of this disease are still unfavorable. Besides, there is still no targeted therapy for osteosarcoma that can be used in clinical settings. Quercetin is a member of the phytochemical family which is used for different diseases including cardiovascular diseases, diabetes, and cancer. Its anti-cancer effects are examined in many types of cancer including breast, colon, lung, prostate, and pancreatic cancers and have shown promising results. Herein, the studies dealing with the antitumor roles of quercetin in osteosarcoma are reviewed in this article. We take a look into quercetin’s ability to affect proliferation, apoptosis, invasion, and chemo-resistance of the osteosarcoma cells through regulating protein expression and signaling pathways.

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Quercetin induces apoptosis in the methotrexate-resistant osteosarcoma cell line U2-OS/MTX300 via mitochondrial dysfunction and dephosphorylation of Akt

Cited by 13 publications

References 24 publications

ROS-Mediated Cancer Cell Killing through Dietary Phytochemicals

ROS-Mediated Cancer Cell Killing through Dietary Phytochemicals

Quercetin Enhances Cisplatin Sensitivity of Human Osteosarcoma Cells by Modulating microRNA-217-KRAS Axis

Anti-cancer properties of quercetin in osteosarcoma

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