Mad1 mediates hypoxia-induced doxorubicin resistance in colon cancer cells by inhibiting mitochondrial function

Cho, Kumsun; Shin, Hyun Woo; Kim, Young Im; Cho, Chung Hyun; Chun, Yang Sook; Kim, Tae You; Park, Jong-Wan

doi:10.1016/j.freeradbiomed.2013.02.022

Cited by 22 publications

(30 citation statements)

References 31 publications

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“…We observed similar mode of action with KP1019. However, the applications of doxorubicin in oncology are limited due its side effects, particularly cardio toxicity [55] and colon cancer cells developed resistance [56,57]. Since KP1019 shares similar property with doxorubicin, hence we propose that KP1019 can be an effective candidate for the treatment of doxorubicin resistant cancerous cells.…”

Section: Discussionmentioning

confidence: 99%

Anti‐cancer drug KP1019 modulates epigenetics and induces DNA damage response in Saccharomyces cerevisiae

et al. 2014

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a b s t r a c t KP1019 comprises a class of ruthenium compounds having promising anticancer activity. Here, we investigated the molecular targets of KP1019 using Saccharomyces cerevisiae as a model organism. Our results revealed that in the absence of the N-terminal tail of histone H3, the growth inhibitory effect of KP1019 was markedly enhanced. Furthermore, H3K56A or rtt109D mutants exhibit hypersensitivity for KP1019. Moreover, KP1019 evicts histones from the mononucleosome and interacts specifically with histone H3. We have also shown that KP1019 treatment causes induction of Ribonucleotide Reductase (RNR) genes and degradation of Sml1p. Our results also suggest that DNA damage induced by KP1019 is primarily repaired through double-strand break repair (DSBR). In summary, KP1019 targets histone proteins, with important consequences for DNA damage responses and epigenetics.

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Section: Discussionmentioning

confidence: 99%

Anti‐cancer drug KP1019 modulates epigenetics and induces DNA damage response in Saccharomyces cerevisiae

et al. 2014

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“…Conversely, overexpression of Mxd1 protects against apoptosis induced by tumor necrosis factor-related apoptosis inducing ligand (TRAIL), Fas ligand, serum withdrawal, UV and cysplatin treatments [113, 117]. Moreover, MXD1 is induced by hypoxia and mediates hypoxia-induced resistance to doxorubicin [188]. Importantly, MXD1 overexpression also specifically inhibits MYC dependent apoptosis upon serum withdrawal [113].…”

Section: Functional Interactions Among Network Membersmentioning

confidence: 99%

“…Moreover, MXD2-mediated, HIF-dependent downregulation of mitochondrial metabolism may provide a survival advantage by reducing ROS levels [196, 198]. Indeed, MXD1 is also induced by hypoxia in colon cancer cells and mediates resistance to doxorubicin under hypoxia [188]. …”

Section: Functional Interactions Among Network Membersmentioning

confidence: 99%

Functional interactions among members of the MAX and MLX transcriptional network during oncogenesis

Diolaiti

McFerrin

Carroll

et al. 2015

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

104

142

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The transcription factor MYC and its related family members MYCN and MYCL have been implicated in the etiology of a wide spectrum of human cancers. Compared to other oncoproteins, such as RAS or SRC, MYC is unique because its protein coding region is rarely mutated. Instead, MYC’s oncogenic properties are unleashed by regulatory mutations leading to unconstrained high levels of expression. Under both normal and pathological conditions MYC regulates multiple aspects of cellular physiology including proliferation, differentiation, apoptosis, growth and metabolism by controlling the expression of thousands of genes. How a single transcription factor exerts such broad effects remains a fascinating puzzle. Notably, MYC is part of a network of bHLHLZ proteins centered on the MYC heterodimeric partner MAX and its counterpart, the MAX-like protein MLX. This network includes MXD1-4, MNT, MGA, MONDOA and MONDOB proteins. With some exceptions, MXD proteins have been functionally linked to cell cycle arrest and differentiation, while MONDO proteins control cellular metabolism. Although the temporal expression patterns of many of these proteins can differ markedly they are frequently expressed simultaneously in the same cellular context, and potentially bind to the same, or similar DNA consensus sequence. Here we review the activities and interactions among these proteins and propose that the broad spectrum of phenotypes elicited by MYC deregulation is intimately connected to the functions and regulation of the other network members. Furthermore, we provide a meta-analysis of TCGA data suggesting that the coordinate regulation of the network is important in MYC driven tumorigenesis.

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“…20 Hypoxia has been shown to reduce the cytotoxic action of doxorubicin via HIF related pathways, the induction of MAX dimerization protein 1 (Mad1) 21 or the induction of the multidrug resistance-associated protein 1 gene (MRP1). 22 It was therefore desired to analyze whether doxorubicin could be loaded to the oxyGG hydrogels during gelation and what amount of it would be released into the surrounding media.…”

Section: Figure 2 Tunable Release Of Either Oxygen or Doxorubicin Camentioning

confidence: 99%

Oxygen-Producing Gellan Gum Hydrogels for Dual Delivery of Either Oxygen or Peroxide with Doxorubicin

Newland

Baeger

Eigel

et al. 2017

ACS Biomater. Sci. Eng.

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Hypoxic environments in the core of tumors can give rise to resistance against anticancer therapeutics. Oxygen-producing biomaterials may be able to improve chemotherapeutic efficiency by locally disrupting the hypoxic environment. We hypothesized that gellan gum hydrogels could be loaded with both a solid peroxide and the chemotherapeutic drug doxorubicin, to release both oxygen and doxorubicin simultaneously. We show that calcium peroxide physically cross-links gellan gum into a hydrogel, which when loaded with catalase raises the dissolved oxygen content of media for up to 64 h. Additionally, doxorubicin could be loaded into the hydrogel in situ, allowing release in well-defined quantities.

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Mad1 mediates hypoxia-induced doxorubicin resistance in colon cancer cells by inhibiting mitochondrial function

Cited by 22 publications

References 31 publications

Anti‐cancer drug KP1019 modulates epigenetics and induces DNA damage response in Saccharomyces cerevisiae

Anti‐cancer drug KP1019 modulates epigenetics and induces DNA damage response in Saccharomyces cerevisiae

Functional interactions among members of the MAX and MLX transcriptional network during oncogenesis

Oxygen-Producing Gellan Gum Hydrogels for Dual Delivery of Either Oxygen or Peroxide with Doxorubicin

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