High aldehyde dehydrogenase activity enhances stem cell features in breast cancer cells by activating hypoxia-inducible factor-2α

Kim, Ran-Ju; Park, Jeong-Ran; Roh, Kyung-Jin; Choi, A-Ram; Kim, Chang Woo; Kim, Pyeung-Hyeun; Yu, Jong Han; Lee, Jong Won; Ahn, Sei-Hyun; Gong, Gyungyub; Hwang, Jae-Woong; Kang, Kyung‐Sun; Kong, Gu; Sheen, Yhun Yhong; Nam, Jeong‐Seok

doi:10.1016/j.canlet.2012.11.026

Cited by 79 publications

(69 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies have suggested that the stem cell markers Oct4 (27), Sca-1 (28), and ALDH1 (29) play important roles in maintaining the pluripotency of BCSCs. In the present study, we established a sphereforming culture system to culture BCSCs as an in vitro model of breast cancer as previously described (30). To confirm whether sphere-forming subpopulations are enriched for stem cell-like properties under 3D culture conditions, we examined the expression profiles of the stem cell markers Oct4, Sca-1, ALDH1, and Sox2.…”

Section: Resultsmentioning

confidence: 99%

Wnt/β-Catenin Small-Molecule Inhibitor CWP232228 Preferentially Inhibits the Growth of Breast Cancer Stem-like Cells

et al. 2015

Self Cite

View full text Add to dashboard Cite

Breast cancer stem cells (BCSC) are resistant to conventional chemotherapy and radiotherapy, which may destroy tumor masses but not all BCSC that can mediate relapses. In the present study, we showed that the level of Wnt/b-catenin signaling in BCSC is relatively higher than in bulk tumor cells, contributing to a relatively higher level of therapeutic resistance. We designed a highly potent small-molecule inhibitor, CWP232228, which antagonizes binding of b-catenin to T-cell factor (TCF) in the nucleus. Notably, although CWP232228 inhibited the growth of both BCSC and bulk tumor cells by inhibiting b-catenin-mediated transcription, BCSC exhibited greater growth inhibition than bulk tumor cells. We also documented evidence of greater insulinlike growth factor-I (IGF-I) expression by BCSC than by bulk tumor cells and that CWP232228 attenuated IGF-I-mediated BCSC functions. These results suggested that the inhibitory effect of CWP232228 on BCSC growth might be achieved through the disruption of IGF-I activity. Taken together, our findings indicate that CWP232228 offers a candidate therapeutic agent for breast cancer that preferentially targets BCSC as well as bulk tumor cells.

show abstract

Section: Resultsmentioning

confidence: 99%

Wnt/β-Catenin Small-Molecule Inhibitor CWP232228 Preferentially Inhibits the Growth of Breast Cancer Stem-like Cells

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…Luciferase activity assays were performed using the Luciferase Assay (Promega, Madison, Wis., USA), as previously described [15]. Briefly, cells in 12-well flat-bottomed plates were transfected with a total of 500 ng/well reporter plasmid and 250 ng/well β-gal plasmid DNA (for normalization) using Lipofectamine 2000 according to the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

“…Immunoblot analysis was performed as previously described [15]. Immunoblot bands were detected and scanned using the luminescent image analyzer Image Quant LAS-4000 (GE Healthcare, Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

PTEN Loss-Mediated Akt Activation Increases the Properties of Cancer Stem-Like Cell Populations in Prostate Cancer

Kim

Bae

Hong³

et al. 2014

Oncology

Self Cite

View full text Add to dashboard Cite

Objective: To demonstrate that the PTEN/PI3K/Akt/NF-κB pathway plays an important role in regulating the prostate cancer stem-like cell population by upregulating ABCG2. Methods: Targeted PTEN knockdown in human prostate DU145 and 22Rv1 cells using a small interfering RNA were confirmed by immunoblot analysis using antibodies of PTEN, phospho-Akt, Akt, and a-tubulin. Knockdown PTEN DU145 and 22Rv1 cells were augmented, and the stem cell-like properties were examined by cell viability and tumor sphere formation and treated by Akt IV inhibitor to provide the signal transduction pathway. Luciferase activity assays were performed. Results: The knockdown of PTEN in prostate cancer cell lines increased the stem-like properties of the cells, including their sphere-forming ability, stem cell population number, epithelial-mesenchymal transition-related gene expression, and ABCG2 expression. Additionally, PTEN expression was highly associated with elevated expression of phospho-Akt. Treatment with an Akt inhibitor suppressed the PTEN-mediated effects on the properties of these stem-like cells as well as drug resistance, ABCG2 expression, and the NF-κB pathway. Conclusion: The loss of PTEN in prostate cancer cells resulted in an increased PI3K/Akt pathway. Due to the Akt activation, PTEN loss may play an important role in prostate cancer by promoting cancer stemness through a mechanism that involves enhanced NF-κB signaling.

show abstract

“…In addition to Hoechst dye staining, aldehyde dehydrogenase (ALDH) can also be used as a functional marker for cancer stem cells [46][47][48] .…”

Section: The Inhibitory Effect Of Combination Nanoparticles On Cancermentioning

confidence: 99%

Co-Eradication of Breast Cancer Cells and Cancer Stem Cells by Cross-Linked Multilamellar Liposomes Enhances Tumor Treatment

Kim

Liu

et al. 2015

Mol. Pharmaceutics

View full text Add to dashboard Cite

The therapeutic limitations of conventional chemotherapeutic drugs have emerged as a challenge for breast cancer therapy; these shortcomings are likely due, at least in part, to the presence of the cancer stem cells (CSCs). Salinomycin, a polyether antibiotic isolated from Streptomyces albus, has been shown to selectively inhibit cancer stem cells; however, its clinical application has been hindered by the drug's hydrophobility, which limits the available administration routes. In this paper, a novel drug delivery system, cross-linked multilamellar liposomal vesicles (cMLVs), was optimized to allow for the codelivery of salinomycin (Sal) and doxorubicin (Dox), targeting both CSCs and breast cancer cells. The results show that the cMLV particles encapsulating different drugs have similar sizes with high encapsulation efficiencies (>80%) for both Dox and Sal. Dox and Sal were released from the particles in a sustained manner, indicating the stability of the cMLVs. Moreover, the inhibition of cMLV(Dox+Sal) against breast cancer cells was stronger than either single-drug treatment. The efficient targeting of cMLV(Dox+Sal) to CSCs was validated through in vitro experiments using breast cancer stem cell markers. In accordance with the in vitro combination treatment, in vivo breast tumor suppression by cMLV(Dox+Sal) was 2-fold more effective than single-drug cMLV treatment or treatment with the combination of cMLV(Dox) and cMLV(Sal). Thus, this study demonstrates that cMLVs represent a novel drug delivery system that can serve as a potential platform for combination therapy, allowing codelivery of an anticancer agent and a CSC inhibitor for the elimination of both breast cancer cells and cancer stem cells.

show abstract

High aldehyde dehydrogenase activity enhances stem cell features in breast cancer cells by activating hypoxia-inducible factor-2α

Cited by 79 publications

References 61 publications

Wnt/β-Catenin Small-Molecule Inhibitor CWP232228 Preferentially Inhibits the Growth of Breast Cancer Stem-like Cells

Wnt/β-Catenin Small-Molecule Inhibitor CWP232228 Preferentially Inhibits the Growth of Breast Cancer Stem-like Cells

PTEN Loss-Mediated Akt Activation Increases the Properties of Cancer Stem-Like Cell Populations in Prostate Cancer

Co-Eradication of Breast Cancer Cells and Cancer Stem Cells by Cross-Linked Multilamellar Liposomes Enhances Tumor Treatment

Contact Info

Product

Resources

About