Leprosy drug clofazimine activates peroxisome proliferator-activated receptor-γ and synergizes with imatinib to inhibit chronic myeloid leukemia cells

Kumar, Harish; Chattopadhyay, Sourav; Das, Nandini; Shree, Sonal; Patel, Dinesh V.; Mohapatra, Jogeswar; Gurjar, Anagha; Kushwaha, Sapana; Singh, Abhishek Kumar; Dubey, Shikha; Lata, Kiran; Kushwaha, Rajesh; Riyazuddin, Mohammed; Dastidar, Krishnarup Ghosh; Yadav, Namrata; Vishwakarma, Achchhe Lal; Gayen, Jiaur R.; Bandyopadhyay, Sanghamitra; Chatterjee, Abhijit; Jain, Mukul; Tripathi, Anil Kumar; Trivedi, Arun Kumar; Chattopadhyay, Naibedya; Ramachandran, Ravishankar; Sanyal, Sabyasachi

doi:10.3324/haematol.2018.194910

Cited by 14 publications

(15 citation statements)

References 66 publications

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“…Clofazimine induces apoptosis in quiescent LSCs by blocking the transcription and translation of Bcl-2. Co-administration of clofazimine with imatinib for 96 h almost completely eradicates LSCs by intensifying the apoptosis of both quiescent and proliferative LSCs [29]. These findings support the potential use of clofazimine in specifically targeting quiescent LSCs.…”

Section: Clofaziminesupporting

confidence: 68%

Advances in therapeutic agents targeting quiescent cancer cells

Nabil

Liu

et al. 2022

Acta Materia Medica

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Quiescent cancer cells (QCCs) reversibly reside in G0 phase, thus allowing them to survive chemotherapy and radiotherapy, which generally target proliferating cells. Surviving QCCs may re-proliferate, and consequently result in cancer progression, recurrence, and metastasis. Therefore, understanding the key players governing QCC survival and activation is crucial for developing QCC-targeting agents. This review presents an overview of (1) the mechanisms underlying the regulation of QCC status and (2) recent advances in the development of QCC-targeting therapeutic agents and their underlying mechanisms. The development of effective therapeutic modalities that target QCCs may enable new cancer treatments to prevent cancer progression and recurrence.

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Section: Clofaziminesupporting

confidence: 68%

Advances in therapeutic agents targeting quiescent cancer cells

Nabil

Liu

et al. 2022

Acta Materia Medica

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“…Moreover, PPARγ activation inhibits 13 various signals, including JAK/STAT (Vallee et al, 2018). The inhibitory effect on leukemia stem cells works by suppressing Stat5 expression (Kumar et al, 2020). The present study showed that JWA deficiency elevated both transcription and translation levels of PPARγ, considering it a reason for Stat5 reduction.…”

Section: Discussionsupporting

confidence: 47%

“…It is made available under a preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in The copyright holder for this this version posted January 21, 2022. ; https://doi.org/10.1101/2022.01.17.476552 doi: bioRxiv preprint 13 various signals, including JAK/STAT (Vallee et al, 2018). The inhibitory effect on leukemia stem cells works by suppressing Stat5 expression (Kumar et al, 2020). The present study showed that JWA deficiency elevated both transcription and translation levels of PPARγ, considering it a reason for Stat5 reduction.…”

Section: Discussionmentioning

confidence: 52%

JWA deficiency accelerates aging through disrupting intestinal epithelial homeostasis via Notch1/PPARγ/Stat5 axis

Zhou

Li²,

et al. 2022

Preprint

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Aging usually suppresses the renewal and regeneration of intestinal epithelium. The imbalance of intestinal epithelial homeostasis may also be a promoter for aging. JWA responds to oxidative stress and repairs damaged DNA; it participates in multiple cellular processes like cell proliferation and differentiation. Here we identified JWA as a new aging-associated gene, whose deletion-accelerated aging in mice was related to intestinal epithelium atrophy. We further knocked out intestinal epithelial JWA and found it disrupted intestinal epithelial homeostasis, thus promoting aging in mice. Mechanistically, we discovered that JWA deficiency promoted Notch1 ubiquitination degradation via ERK/Fbxw7 cascade and interfered with the PPARγ/Stat5 signal axis. This reduced the intestinal stem cell function and altered the intestinal epithelial cell lineage distribution, finally suppressing the renewal and regeneration of intestinal epithelium. Our results demonstrated that JWA is a new aging-associated gene essential for the renewal and regeneration of intestinal epithelium. We also provide a new idea that maintaining intestinal epithelial homeostasis may be a potential anti-aging strategy in humans or mammals.

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“…Clofazamine showed anti-leukemic potential in CML by modulating transcriptional activity of PPARγ and its subsequent interaction with p65 NF-κB to induce degradation. Degradation of p65 decreased transcription of myeloblastoma oncoprotein (MYB), which led to the downregulation of peroxiredoxin 1 (PRDX1) with enhanced reactive oxygen species (ROS) induced apoptosis [ 171 ].…”

Section: Targeting Wnt Signalingmentioning

confidence: 99%

Wnt Signaling in Leukemia and Its Bone Marrow Microenvironment

Ruan

Kim

Ogana

et al. 2020

IJMS

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Leukemia is an aggressive hematologic neoplastic disease. Therapy-resistant leukemic stem cells (LSCs) may contribute to the relapse of the disease. LSCs are thought to be protected in the leukemia microenvironment, mainly consisting of mesenchymal stem/stromal cells (MSC), endothelial cells, and osteoblasts. Canonical and noncanonical Wnt pathways play a critical role in the maintenance of normal hematopoietic stem cells (HSC) and LSCs. In this review, we summarize recent findings on the role of Wnt signaling in leukemia and its microenvironment and provide information on the currently available strategies for targeting Wnt signaling.

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Leprosy drug clofazimine activates peroxisome proliferator-activated receptor-γ and synergizes with imatinib to inhibit chronic myeloid leukemia cells

Cited by 14 publications

References 66 publications

Advances in therapeutic agents targeting quiescent cancer cells

Advances in therapeutic agents targeting quiescent cancer cells

JWA deficiency accelerates aging through disrupting intestinal epithelial homeostasis via Notch1/PPARγ/Stat5 axis

Wnt Signaling in Leukemia and Its Bone Marrow Microenvironment

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