Daunorubicin can eliminate iPS-derived cancer stem cells via ICAD/CAD-independent DNA fragmentation

Seno, Akimasa; Mizutani, Akifumi; Aizawa, Kazuki; Onoue, Ryoma; Masuda, Junko; Ochi, Naotaka; Taniguchi, Saki; Sota, Tatsuyuki; Hiramoto, Yuki; Michiue, Taisuke; Nair, Nisha; Seno, Masaharu

doi:10.20517/cdr.2019.01

Cited by 4 publications

(5 citation statements)

References 45 publications

(78 reference statements)

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“…The IC 50 s for gemcitabine was approximately 10 folds higher than that reported in previous studies while doxorubicin showed IC 50 s on these cells at around 50 to 100 nM, which is feasibly low to be a candidate as drug targeting CSCs [27]. This result is consistent with our previous report [30]. These differences could be traced to the mechanism of action of the two drugs, of which efficacy is depending on the cell phenotypes.…”

Section: Discussionsupporting

confidence: 91%

Different pancreatic cancer microenvironments convert iPSCs into cancer stem cells exhibiting distinct plasticity with altered gene expression of metabolic pathways

Hassan

Ohara

Afify

et al. 2022

J Exp Clin Cancer Res

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Background Cancer stem cells (CSCs) are generated under irregular microenvironment in vivo, of which mimic is quite difficult due to the lack of enough information of the factors responsible for cancer initiation. Here, we demonstrated that mouse induced pluripotent cells (miPSCs) reprogrammed from normal embryonic fibroblasts were susceptible to the microenvironment affected by cancer cells to convert into CSCs in vivo. Methods Three different pancreatic cancer line cells, BxPC3, PANC1, and PK8 cells were mixed with miPSCs and subcutaneously injected into immunodeficient mice. Tumors were evaluated by histological analysis and cells derived from iPSCs were isolated and selected from tumors. The isolated cells were characterized for cancer stem cell characters in vitro and in vivo as well as their responses to anticancer drugs. The impact of co-injection of iPSCs with cancer cells on transcriptome and signaling pathways of iPSCs was investigated. Results The injection of miPSCs mixed with human pancreatic cancer cells into immunodeficient mice maintained the stemness of miPSCs and changed their phenotype. The miPSCs acquired CSC characteristics of tumorigenicity and self-renewal. The drug responses and the metastatic ability of CSCs converted from miPSCs varied depending on the microenvironment of cancer cells. Interestingly, transcriptome profiles of these cells indicated that the pathways related with aggressiveness and energy production were upregulated from the levels of miPSCs. Conclusions Our result suggests that cancer-inducing microenvironment in vivo could rewire the cell signaling and metabolic pathways to convert normal stem cells into CSCs.

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Section: Discussionsupporting

confidence: 91%

Different pancreatic cancer microenvironments convert iPSCs into cancer stem cells exhibiting distinct plasticity with altered gene expression of metabolic pathways

Hassan

Ohara

Afify

et al. 2022

J Exp Clin Cancer Res

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“…And this method allowed us to establish CSC models under various conditions of microenvironments so that it becomes possible to evaluate the efficacy of the drugs against CSCs in easier ways than before. [2][3][4] Currently, many aspects of the targets in a CSC are conceivable to design a drug against CSCs. 5 Sometimes the apoptosis inhibiting topoisomerase with daunorubicin/doxorubicin, 4 sometimes the dynamics of tubulins inhibiting with Paclitaxel and others cytoplasmic signaling have been evaluated.…”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4] Currently, many aspects of the targets in a CSC are conceivable to design a drug against CSCs. 5 Sometimes the apoptosis inhibiting topoisomerase with daunorubicin/doxorubicin, 4 sometimes the dynamics of tubulins inhibiting with Paclitaxel and others cytoplasmic signaling have been evaluated. 6 The metabolic pathways are also considered as good target candidates.…”

Section: Introductionmentioning

confidence: 99%

“…The CSCs derived from iPSCs can reflect the patient genetic background than those obtained from experimental genetic manipulation. And this method allowed us to establish CSC models under various conditions of microenvironments so that it becomes possible to evaluate the efficacy of the drugs against CSCs in easier ways than before 2–4 . Currently, many aspects of the targets in a CSC are conceivable to design a drug against CSCs 5 .…”

Section: Introductionmentioning

confidence: 99%

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Diphenyleneiodonium efficiently inhibits the characteristics of a cancer stem cell model derived from induced pluripotent stem cells

Monzur

Hassan

Afify

et al. 2022

Cell Biochemistry & Function

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Diphenyleneiodonium (DPI) has long been evaluated as an anticancer drug inhibiting NADPH oxidase, the IC 50 in several cancer cell lines was reported 10 µM, which is too high for efficacy. In this study, we employed miPS-Huh7cmP cells, which we previously established as a cancer stem cell (CSC) model from induced pluripotent stem cells, to reevaluate the efficacy of DPI because CSCs are currently one of the main foci of therapeutic strategy to treat cancer, but generally considered resistant to chemotherapy. As a result, the conventional assay for the cell growth inhibition by DPI accounted for an IC 50 at 712 nM that was not enough to define the effectiveness as an anticancer drug. Simultaneously, the wound-healing assay revealed an IC 50 of approximately 500 nM. Comparatively, the IC 50 values shown on sphere formation, colony formation, and tube formation assays were 5.52, 12, and 8.7 nM, respectively. However, these inhibitory effects were not observed by VAS2780, also a reputed NADPH oxidase inhibitor. It is noteworthy that these three assays are evaluating the characteristic of CSCs and are designed in the three-dimensional (3D) culture methods. We concluded that DPI could be a suitable candidate to target mitochondrial respiration in CSCs. We propose that the 3D culture assays are more efficient to screen anti-CSC drug candidates and better mimic tumor

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“…Such knowledge is essential to design future therapies to overcome cancer drug resistance. On a similar topic, the research article by Seno et al [14] describes the cytotoxic action of daunorubicin, a topoisomerase II inhibitor, against mouse induced pluripotent stem cells-derived cancer stem cells.…”

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confidence: 99%

Epigenetic basis of cancer drug resistance

Aziz¹,

Ahmad²

2020

CDR

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Daunorubicin can eliminate iPS-derived cancer stem cells via ICAD/CAD-independent DNA fragmentation

Abstract: can eliminate iPS-derived cancer stem cells via ICAD/CAD-independent DNA fragmentation.

Cited by 4 publications

References 45 publications

Different pancreatic cancer microenvironments convert iPSCs into cancer stem cells exhibiting distinct plasticity with altered gene expression of metabolic pathways

Different pancreatic cancer microenvironments convert iPSCs into cancer stem cells exhibiting distinct plasticity with altered gene expression of metabolic pathways

Diphenyleneiodonium efficiently inhibits the characteristics of a cancer stem cell model derived from induced pluripotent stem cells

Epigenetic basis of cancer drug resistance

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