8-Bromo-7-methoxychrysin-blocked STAT3/Twist axis inhibits the stemness of cancer stem cell-like cell originated from SMMC-7721 cells

Luo, Yukun; Cui, Yinghong; Cao, Xiaocheng; Li, Xiang; Chen, A; Zhang, Jiansong; Chen, Xiang-Ding; Cao, Ji

doi:10.1093/abbs/gmx025

Cited by 8 publications

(9 citation statements)

References 32 publications

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“…3 , 4 To date, it has been confirmed that epithelial-mesenchymal transition (EMT), an embryonic developmental process, confers stem-cell like features to cancer cells. 5 , 6 Therefore, the development of agents targeting CSLCs to reverse EMT deserves further attention.…”

Section: Introductionmentioning

confidence: 99%

Modulation of MnSOD and FoxM1 Is Involved in Invasion and EMT Suppression by Isovitexin in Hepatocellular Carcinoma Cells

Qiu¹,

Cao²,

Liu³

et al. 2020

CMAR

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Background Manganese superoxide dismutase (MnSOD) induces FoxM1 expression, subsequently contributing to migration in several cancer cells. Isovitexin (ISOV) was recently found to downregulate MnSOD and FoxM1, decreasing stemness in hepatocellular carcinoma (HCC) stem-like cells (HCSLCs). The current study aimed to determine whether inhibition of migration, invasion and EMT in HCSLCs by ISOV results from MnSOD/FoxM1 signaling blockade and subsequent Twist1, Slug, ZEB1 and MMP-2 downregulation. Materials and Methods We examined the migratory and invasive capabilities and EMT phenotype in HCC cells and their HCSLCs, respectively, by wound-healing assay, transwell invasion assay and Western blot after treatment with non-cytotoxic concentrations of ISOV, and explored the mechanism by which ISOV affects migration, invasion and EMT by MnSOD or FoxM1 knockdown and/or overexpression in HCSLCs or HCC cells. Results The results showed that ISOV not only downregulated MnSOD and FoxM1 but also suppressed the migratory and invasive capabilities and reversed the EMT phenotype in HCSLCs, which was reflected by elevated E-cadherin protein amounts, and reduced N-cadherin, Twist1, Slug, ZEB1 and MMP-2 protein levels. The suppressive effects of ISOV on the migratory and invasive capabilities and EMT phenotype could be potentiated by MnSOD or FoxM1 knockdown in HCSLCs, and attenuated by MnSOD or FoxM1 overexpression in HCC cells. Importantly, FoxM1 overexpression reversed MnSOD knockdown combined with ISOV suppression on the migratory and invasive capabilities and EMT phenotype in HCSLCs, while having little effects on MnSOD expression. Conclusion Collectively, the above findings demonstrated that ISOV suppresses migration, invasion and EMT in HCSLCs by blocking MnSOD/FoxM1 signaling subsequently inhibiting the expression of EMT-related transcription factors and MMP-2.

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Section: Introductionmentioning

confidence: 99%

Modulation of MnSOD and FoxM1 Is Involved in Invasion and EMT Suppression by Isovitexin in Hepatocellular Carcinoma Cells

Qiu¹,

Cao²,

Liu³

et al. 2020

CMAR

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“…Additionally Lirdprapamongkol et al found that chrysin overcame TRAIL resistance of cancer cells mainly as blocking STAT3 25. Our recent study demonstrated that chrysin inhibited the sphere formation capability of SKOV3-derived ovarian cancer stem-like cells (CSLCs),26 and 8-Bromo-7-methoxychrysin, a synthetic analog of chrysin,27 reduced sphere-forming rate of the spheres originated from SMMC-7721 cells by blocking STAT3/Twist axis 28. However, the mechanisms underlying the regulation of STAT3 activation by chrysin are also unclear.…”

Section: Introductionmentioning

confidence: 80%

“…Previous study demonstrated that 8-Bromo-7-methoxychrysin could inhibit the stemness of CSLCs derived from SMMC-7721 cells by blocking the STAT3/Twist axis 28. Many studies have found that SHP-1 tumor suppression may result from its direct downregulating of p-STAT3 Tyr705.…”

Section: Resultsmentioning

confidence: 99%

Chrysin inhibits sphere formation in SMMC-7721 cells via modulation of SHP-1/STAT3 signaling pathway

Zhang

Chen

Xiao

et al. 2019

CMAR

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Background: Chrysin is a natural flavonoid which has been identified as a candidate anti-cancer agent due to its inhibitory effect on a variety of cancer cells, including targeted inhibition of sphere formation in hepatocellular carcinoma (HCC) cell lines. However, the mechanism by which chrysin modulates HCC spheres remains unclear. Materials and methods: In this study, we investigate the effect of chrysin on the regulation of SHP-1 and its downstream signal molecule STAT3 to explain the mechanism by which chrysin inhibits sphere formation of HCC cell lines. Results: Here, we found that SHP-1 protein expression was markedly down-regulated in the spheres from both SMMC-7721 and MHCC97H cells. Chrysin significantly inhibited sphere formation and upregulated the expression of SHP-1 protein in both SMMC-7721 and MHCC97H cells, as well as reduced p-STAT3 and Twist1 expressions in SMMC-7721 cells. Furthermore, knockdown of SHP-1 in SMMC-7721 cells resulted in the induction of p-STAT3 and Twist1 protein expression and antagonizing the inhibitory effect of chrysin on sphere formation in SMMC-7721 cells. Conclusion: Overall, the study findings demonstrated that chrysin acts as a candidate for the treatment of HCC through modulating SHP-1/STAT3 signaling pathway.

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“…The wound-healing assay was performed as previously described ( 35 ). Briefly, H460, A549 cells or their corresponding LCSLCs were seeded (2×10 5 cells/well) into a 6-well plate.…”

Section: Methodsmentioning

confidence: 99%

Genistein inhibits lung cancer cell stem‑like characteristics by modulating MnSOD and FoxM1 expression

Cao

Liu

et al. 2020

Oncol Lett

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Manganese superoxide dismutase (MnSOD) promotes invasive and migratory activities by upregulating Forkhead box protein M1 (FoxM1) expression. The present study investigated whether modulation of MnSOD and FoxM1 expression was responsible for the antitumor effects of genistein on cancer stem-like cells (CSLCs) derived from non-small cell lung cancer cells (NSCLCs). Spheroids prepared from H460 or A549 cells were defined as lung cancer stem-like cells (LCSLCs) and were treated with genistein. The Cell Counting Kit-8 assay was performed to assess human lung fibroblast IMR-90 cell proliferation, as well as NSCLC H460 and A549 cell proliferation following treatment with genistein. MnSOD, FoxM1, cluster of differentiation (CD)133, CD44, BMI1 proto-oncogene, polycomb ring finger (Bmi1) and Nanog homeobox (Nanog) protein expression levels were examined via western blotting. The sphere formation assay was conducted to evaluate LCSLC self-renewal potential, and LSCLC migratory and invasive activities were analyzed using the wound healing and Transwell invasion assays, respectively. Knockdown and overexpression of MnSOD and FOXM1 via short hairpin-RNA or cDNA transfection were performed. The results indicated that genistein (80 and 100 µM) suppressed H460 and A549 cell viability compared with IMR-90 cells. Sub-cytotoxic concentrations of genistein (20 and 40 µM) inhibited sphere formation activity and decreased the protein expression levels of CD133, CD44, Bmi1 and Nanog in LCSLCs compared with the control group. Genistein also suppressed the migratory and invasive activities of LCSLCs compared with the control group. MnSOD and FoxM1 overexpression antagonized the effects of genistein (40 µM), whereas MnSOD and FoxM1 knockdown enhanced the inhibitory effects of genistein (20 µM) on CSLC characteristics of LCSLCs. Overall, the results suggested that genistein suppressed lung cancer cell CSLC characteristics by modulating MnSOD and FoxM1 expression levels.

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8-Bromo-7-methoxychrysin-blocked STAT3/Twist axis inhibits the stemness of cancer stem cell-like cell originated from SMMC-7721 cells

Cited by 8 publications

References 32 publications

<p>Modulation of MnSOD and FoxM1 Is Involved in Invasion and EMT Suppression by Isovitexin in Hepatocellular Carcinoma Cells</p>

<p>Modulation of MnSOD and FoxM1 Is Involved in Invasion and EMT Suppression by Isovitexin in Hepatocellular Carcinoma Cells</p>

<p>Chrysin inhibits sphere formation in SMMC-7721 cells via modulation of SHP-1/STAT3 signaling pathway</p>

Genistein inhibits lung cancer cell stem‑like characteristics by modulating MnSOD and FoxM1 expression

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