The opposite effects of doxorubicin on bone marrow stem cells versus breast cancer stem cells depend on glucosylceramide synthase

Bhinge, Kaustubh N.; Gupta, Vineet; Hosain, Salman B.; Satyanarayanajois, Seetharama D.; Meyer, Sharon A.; Blaylock, Benny L.; Zhang, Qianjin; Liu, Yong‐Yu

doi:10.1016/j.biocel.2012.06.010

Cited by 34 publications

(33 citation statements)

References 54 publications

(84 reference statements)

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“…The present study found GCS and Gb3 overproduced in BCSCs, not normal adult stem cells, such as mammary epithelial stem cells (Fig. 3) and bone marrow stem cells reported by another study (68). It is not clear by which molecular mechanism CSCs regain ability in ceramide glycosylation that exists in ESCs.…”

Section: Discussionmentioning

confidence: 59%

“…It has been reported that CSCs (CD55 hi ) have high tolerance to ceramide-induced apoptosis, and this resistance is attributed to abundance of sphingomyelin synthase 1 that can converts ceramide to sphingomyelin (67). Because GCS level is higher in BCSCs versus lower in bone marrow stem cells, doxorubicin can enhance BCSC number and decrease the number of bone marrow stem cells (68). Numerous studies show that GSLs, such as Gb5 and MSGb5, are markers of stem cells; however, no cutting evidence links their expression to a role in pluripotency, and their molecular functions remain unclear.…”

Section: Discussionmentioning

confidence: 99%

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Ceramide Glycosylation by Glucosylceramide Synthase Selectively Maintains the Properties of Breast Cancer Stem Cells

Gupta

Bhinge

Hosain

et al. 2012

Journal of Biological Chemistry

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Background: Glucosylceramide synthase catalyzes ceramide glycosylation that regulates the synthesis of glycosphingolipids. Results: Increased globo-series glycosphingolipids in breast cancer stem cells activate c-Src signaling and ␤-catenin-mediated transcription up-regulating stem cell factors. Conclusion: Ceramide glycosylation maintains the stemness of cancer stem cells. Significance: Glycosphingolipids in cell membrane actively participate in maintaining cancer stem cells.

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Ceramide Glycosylation by Glucosylceramide Synthase Selectively Maintains the Properties of Breast Cancer Stem Cells

Gupta

Bhinge

Hosain

et al. 2012

Journal of Biological Chemistry

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“…Estrogen (17 β ‐estradiol) pellets (0.72 mg, 90‐day release) were implanted subcutaneously in all the mice under anesthesia. BT‐474 cells suspended in serum‐free RPMI‐1640 medium were injected into the second left mammary gland, orthotopically (nearly 2 million cells per mouse) as described by our collaborator in an earlier study . Animals were monitored daily, and body weight was measured.…”

Section: Methodsmentioning

confidence: 99%

Novel Peptidomimetics for Inhibition of HER2:HER3 Heterodimerization in HER2‐Positive Breast Cancer

et al. 2014

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The current approach to treating HER2-overexpressed breast cancer is the use of monoclonal antibodies or a combination of antibodies with traditional chemotherapeutic agents or kinase inhibitors. Our approach is to target clinically validated HER2 domain IV with peptidomimetics and inhibit the protein-protein interactions (PPI) of HERs. Unlike antibodies, peptidomimetics have advantages in terms of stability, modification, and molecular size. We have designed peptidomimetics (compounds 5 and 9) that bind to HER2 domain IV, inhibit protein-protein interactions, and decrease cell viability in breast cancer cells with HER2 overexpression. We have shown, using enzyme fragment complementation and proximity ligation assays, that peptidomimetics inhibit the PPI of HER2:HER3. Compounds 5 and 9 suppressed the tumor growth in a xenograft mouse model. Furthermore, we have shown that these compounds inhibit PPI of HER2:HER3 and phosphorylation of HER2 as compared to control in tissue samples derived from in vivo studies. The stability of the compounds was also investigated in mouse serum, and the compounds exhibited stability with a half-life of up to 3 h. These results suggest that the novel peptidomimetics we have developed target the extracellular domain of HER2 protein and inhibit HER2:HER3 interaction, providing a novel method to treat HER2-positive cancer.

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“…In order to assay the antimutagenic/mutagenic effect of mangaba fruit pulp in mice, an experiment was designed that involved administration of the drugs doxorubicin chloride (DXR) in experiment 1, and 1,2-dimethylhydrazine dihydrochloride (DMH) in experiment 2, whose main target tissues are in the bone marrow (Antunes & Takahashi, 1998;Bhinge et al, 2012;Gibaud, Andreaux, Weingarten, Renard & Couvreur, 1994) and colon (Vanhauwaert, Vanparys & Kirsch-Volders, 2001;Weisburger, Reddy;Wynder, 1977;Fiala, 1977;Newell & Heddle, 2004), respectively.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

First evaluation of the antimutagenic effect of mangaba fruit in vivo and its phenolic profile identification

Lima

Azevedo

Souza

et al. 2015

Food Research International

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The opposite effects of doxorubicin on bone marrow stem cells versus breast cancer stem cells depend on glucosylceramide synthase

Cited by 34 publications

References 54 publications

Ceramide Glycosylation by Glucosylceramide Synthase Selectively Maintains the Properties of Breast Cancer Stem Cells

Ceramide Glycosylation by Glucosylceramide Synthase Selectively Maintains the Properties of Breast Cancer Stem Cells

Novel Peptidomimetics for Inhibition of HER2:HER3 Heterodimerization in HER2‐Positive Breast Cancer

First evaluation of the antimutagenic effect of mangaba fruit in vivo and its phenolic profile identification

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