Clioquinol as an inhibitor of JmjC-histone demethylase exhibits common and unique histone methylome and transcriptome between clioquinol and hypoxia

Moon, Yunwon; Chae, Sehyun; Yim, Sujin; Yang, Eun Gyeong; Choe, Juhui; Hyun, Jiyeon; Chang, Rakwoo; Hwang, Daehee; Park, Hyunsung

doi:10.1016/j.isci.2022.104517

Cited by 1 publication

(2 citation statements)

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“…CLQ was proven an effective HIF-1α activator . The activation of the HIF-1α/Beclin1 signaling pathway would promote autophagy flux .…”

Section: Results and Discussionmentioning

confidence: 99%

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Development of Clioquinol Platinum(IV) Conjugates as Autophagy-Targeted Antimetastatic Agents

Zhang

et al. 2023

J. Med. Chem.

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A series of autophagy-targeted antimetastatic clioquinol (CLQ) platinum(IV) conjugates were designed and prepared by incorporating an autophagy activator CLQ into the platinum(IV) system. Complex 5 with the cisplatin core bearing dual CLQ ligands with potent antitumor properties was screened out as a candidate. More importantly, it displayed potent antimetastatic properties both in vitro and in vivo as expected. Mechanism investigation manifested that complex 5 induced serious DNA damage to increase γ-H2AX and P53 expression and caused mitochondria-mediated apoptosis through the Bcl-2/Bax/caspase3 pathway. Then, it promoted prodeath autophagy by suppressing PI3K/AKT/mTOR signaling and activating the HIF-1α/ Beclin1 pathway. The T-cell immunity was elevated by restraining the PD-L1 expression and subsequently increasing CD3 + and CD8 + T cells. Ultimately, metastasis of tumor cells was suppressed by the synergistic effects of DNA damage, autophagy promotion, and immune activation aroused by CLQ platinum(IV) complexes. Key proteins VEGFA, MMP-9, and CD34 tightly associated with angiogenesis and metastasis were downregulated.

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“…CLQ was proven an effective HIF-1α activator . The activation of the HIF-1α/Beclin1 signaling pathway would promote autophagy flux .…”

Section: Results and Discussionmentioning

confidence: 99%

“…CLQ was proven an effective HIF-1α activator. 42 The activation of the HIF-1α/Beclin1 signaling pathway would promote autophagy flux. 43 Meanwhile, the downregulated expression of mTOR would also increase Beclin1 expression.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Development of Clioquinol Platinum(IV) Conjugates as Autophagy-Targeted Antimetastatic Agents

Zhang

et al. 2023

J. Med. Chem.

View full text Add to dashboard Cite

show abstract

Clioquinol as an inhibitor of JmjC-histone demethylase exhibits common and unique histone methylome and transcriptome between clioquinol and hypoxia

Cited by 1 publication

References 62 publications

Development of Clioquinol Platinum(IV) Conjugates as Autophagy-Targeted Antimetastatic Agents

Development of Clioquinol Platinum(IV) Conjugates as Autophagy-Targeted Antimetastatic Agents

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