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8-bromo-7-methoxychrysin targets NF-?B and FoxM1 to inhibit lung cancer stem cells induced by pro-inflammatory factors.

ABSTRACT: We have previously reported that 8-bromo-7-methoxychrysin (BrMC), a novel synthetic derivative of chrysin, was demonstrated anti-tumor activities against several human cancers, including lung cancer. Interaction between inflammation and cancer stem cell are recently increasingly recognized in tumorigenesis and progression. The purpose of this study was to investigate whether BrMC inhibits lung cancer stemness of H460 cells induced by inflammatory factors (TGF-? combined with TNF-?) and its potential mechanism. Our results showed that BrMC inhibited lung cancer stemness, as validated by enhanced self-renewal ability, higher in vitro tumorigenicity, and increased expression of CD133, CD44, Bmi1 and Oct4 in H460 cells administered TNF-? after prolonged induction by TGF-?, in a concentration-dependent manner. Both NF-?B inhibition by SN50 and FoxM1 suppression by thiostrepton (THI) prompted the inhibition of BrMC on lung CSCs. Conversely, overexpression of NF-?Bp65 significantly antagonized the above effects of BrMC. Meanwhile, overexpression of FoxM1 also significantly compromised BrMC function on suppression of FoxM1 and NF-?Bp65 as well as stemness of lung CSCs. Our results suggest that activation of NF-?B and FoxM1 by cytokines facilitate the acquisition CSCs phenotype, and compromise the chemical inhibition, which may represent an effective therapeutic target for treatment of human lung cancer. Moreover, BrMC may be a potential promising candidate for targeting NF-?B/ FoxM1 to prevent the tumorigenesis under inflammatory microenvironment.

SUBMITTER: Yuan Q

PROVIDER: S-EPMC6775618 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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8-bromo-7-methoxychrysin targets NF-κB and FoxM1 to inhibit lung cancer stem cells induced by pro-inflammatory factors.

Yuan Qing Q Wen Min M Xu Chang C Chen A A Qiu Ye-Bei YB Cao Jian-Guo JG Zhang Jian-Song JS Song Zhen-Wei ZW

Journal of Cancer 20190828 21

We have previously reported that 8-bromo-7-methoxychrysin (BrMC), a novel synthetic derivative of chrysin, was demonstrated anti-tumor activities against several human cancers, including lung cancer. Interaction between inflammation and cancer stem cell are recently increasingly recognized in tumorigenesis and progression. The purpose of this study was to investigate whether BrMC inhibits lung cancer stemness of H460 cells induced by inflammatory factors (TGF-β combined with TNF-α) and its poten ...[more]

PMID: 31602275

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Dataset Information

8-bromo-7-methoxychrysin targets NF-?B and FoxM1 to inhibit lung cancer stem cells induced by pro-inflammatory factors.

Publications

8-bromo-7-methoxychrysin targets NF-κB and FoxM1 to inhibit lung cancer stem cells induced by pro-inflammatory factors.

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