Quercetin Suppresses Drug-Resistant Spheres via the p38 MAPK–Hsp27 Apoptotic Pathway in Oral Cancer Cells

Chen, Su-Feng; Nieh, Shin; Jao, Shu-Wen; Liu, Chia‐Lin; Wu, Chien-Hua; Chang, Yun-Ching; Yang, Chin-Yuh; Lin, Yaoh‐Shiang

doi:10.1371/journal.pone.0049275

Cited by 92 publications

(80 citation statements)

References 33 publications

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“…MAPK plays important roles in regulating apoptosis, and cell death (Robinson and Cobb, 1997), and quercetin plays a critical role in modulating cancer cell survival through p38 MAPK pathway (Chen et al, 2012). These finding support that p38 MAPK plays a critical role in FEOJ-induced apoptosis.…”

Section: Discussionsupporting

confidence: 54%

Flavonoids from Orostachys Japonicus A. Berger Induces Caspase-dependent Apoptosis at Least Partly through Activation of p38 MAPK Pathway in U937 Human Leukemic Cells

Lee¹,

Yun²,

Nagappan³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Section: Discussionsupporting

confidence: 54%

Flavonoids from Orostachys Japonicus A. Berger Induces Caspase-dependent Apoptosis at Least Partly through Activation of p38 MAPK Pathway in U937 Human Leukemic Cells

Lee¹,

Yun²,

Nagappan³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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“…25 Treatment failures resulting in the development of a second primary tumor have urged for the novel non-toxic natural approaches to target CSCs for treatment of cancer. [27][28][29][30]31,32 Lectins have undergone advanced research in Asia comprising China and India and Europe as an alternative tumor therapy, 19 but more work has to be done to target CSCs. This work underpins the antineoplastic potential of AGG, an RIPII family member that inhibits proliferation and plasticity of orospheres and triggers ROS-mediated caspase-dependent apoptotic type-I programmed cell death.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, sulforaphane, cucurbitacin I, resveratrol, quercetin, and curcumin have been reported to suppress the CSCs by inducing apoptosis. 22,28,30,31,32 The proliferation of colon CSCs was eliminated by 20 (s)-ginsenoside Rg3 by induction of apoptosis through caspase-9 and caspase-3 pathways. 34 In CD133 + rectal CSCs, curcumin was found to induce apoptosis and significantly increased its radiosensitivity.…”

Section: Discussionmentioning

confidence: 99%

Abrus agglutinin targets cancer stem-like cells by eliminating self-renewal capacity accompanied with apoptosis in oral squamous cell carcinoma

et al. 2017

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The accumulating evidences show that Abrus agglutinin, a plant lectin, displays a broad range of anticancer activity including cancer-specific induction of apoptosis; however, the underlying molecular mechanism of Abrus agglutinin-induced oral cancer stem cell elimination remains elusive. Our data documented that Abrus agglutinin effectively downregulated the CD44 + expression with the increased CD44 − population in different oral cancer cells. After 24-h Abrus agglutinin treatment, FaDu cells were quantified for orosphere formation in ultra-low attachment plates and data showed that Abrus agglutinin inhibited the number and size of orosphere in a dose-dependent manner in FaDu cells. Furthermore, Abrus agglutinin hindered the plasticity of FaDu orospheres as supported by reduced sphere formation and downregulated the self-renewal property via inhibition of Wnt-β-catenin signaling pathway. Introduction of LiCl, a glycogen synthase kinase 3β inhibitor, rescued the Abrus agglutinin-stimulated inhibition of β-catenin and phosphorylated glycogen synthase kinase 3β in FaDu cell-derived orospheres confirming importance of Wnt signaling in Abrus agglutinin-mediated inhibition of stemness. In this connection, our data showed that Abrus agglutinin restrained proliferation and induced apoptosis in FaDu-derived cancer stem cells in dose-dependent manner. Moreover, western blot data demonstrated that Abrus agglutinin increased the Bax/Bcl-2 ratio with activation of poly(adenosine diphosphate-ribose) polymerase and caspase-3 favoring apoptosis induction in orospheres. Abrus agglutinin induced reactive oxygen species accumulation in orospheres and pretreatment of N-acetyl cysteine, and a reactive oxygen species scavenger inhibited Abrus agglutinin-mediated caspase-3 activity and β-catenin expression indicating reactive oxygen species as a principal regulator of Wnt signaling and apoptosis. In conclusion, Abrus agglutinin has a potential role as an integrative therapeutic approach for combating oral cancer through targeting self-renewability of orospheres via reactive oxygen species-mediated apoptosis.

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“…Hsp27 is a member of the small heat shock protein family and has been found to increase tumorigenicity or induce treatment resistance and apoptosis inhibition [10][11][12] . It has been reported to be associated with drug resistance of breast cancer, oral cancer and non-small cell lung carcinoma (NSCLC) [11,13,14] . Recently, the inhibition of Hsp27 was also reported to enhance the chemosensitivity of glioma to TMZ [15] .…”

Section: Introductionmentioning

confidence: 99%

Quercetin sensitizes human glioblastoma cells to temozolomide in vitro via inhibition of Hsp27

Sang

Lan

2014

Acta Pharmacol Sin

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Aim: Quercetin is an effective Hsp27 inhibitor and has been reported to facilitate tumor cell apoptosis. The aim of this study was to investigate whether quercetin could sensitize human glioblastoma cells to temozolomide (TMZ) in vitro. Methods: Both U251 and U87 human glioblastoma cells were treated with quercetin and/or TMZ for 48 h. Cell viability was detected using the MTT assay. Cell apoptosis was analyzed with caspase-3 activity kits and flow cytometry. Hsp27 expression and phosphorylation were examined using Western blot analysis. RNA interference using Hsp27 siRNA oligos was performed to knock down the gene expression of Hsp27. Results: TMZ (200 or 400 μmol/L) alone effectively inhibited the viability of U251 and U87 cells. When combined with quercetin (30 μmol/L), TMZ (100 μmol/L) significantly inhibited the cell viability, and the inhibition of TMZ (200 and 400 μmol/L) was enhanced. TMZ or quercetin anole did not affect caspase-3 activity and cell apoptosis, while TMZ combined with quercetin significantly increased caspase-3 activity and induced cell apoptosis. TMZ anole significantly increased Hsp27 phosphorylation in U251 and U87 cells, while quercetin or Hsp27 siRNA oligos combined with TMZ attenuated TMZ-induced Hsp27 phosphorylation and significantly inhibited Hsp27 expression. Conclusion: Combined treatment with TMZ and quercetin efficiently suppressed human glioblastoma cell survival in vitro.

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Quercetin Suppresses Drug-Resistant Spheres via the p38 MAPK–Hsp27 Apoptotic Pathway in Oral Cancer Cells

Cited by 92 publications

References 33 publications

Flavonoids from Orostachys Japonicus A. Berger Induces Caspase-dependent Apoptosis at Least Partly through Activation of p38 MAPK Pathway in U937 Human Leukemic Cells

Flavonoids from Orostachys Japonicus A. Berger Induces Caspase-dependent Apoptosis at Least Partly through Activation of p38 MAPK Pathway in U937 Human Leukemic Cells

Abrus agglutinin targets cancer stem-like cells by eliminating self-renewal capacity accompanied with apoptosis in oral squamous cell carcinoma

Quercetin sensitizes human glioblastoma cells to temozolomide in vitro via inhibition of Hsp27

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