Prostate and Colon Cancer Stem Cells as a Target for Anti-Cancer Drug Development

Botchkina, Galina I.; Ojima, Iwao

doi:10.5772/15622

Cited by 4 publications

(1 citation statement)

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“…Such conditions include growing on type I collagen-coated surface or in 3D type I collagen-containing culture, in stem cell serum-free medium, at low cell density and with repeated sets of cell sorting. The stemness features of cells grown under these conditions were demonstrated in our previous functional and genomics studies [25,30-32]. In particular, we have found the overactivation of several developmental cascades, such as Hedgehog, EGFR, Wnt/β-catenin and Notch, which was linked with prostate stem cell regulation [33-35] and the progression of prostate cancer to androgen-independence and metastasis [36,37].…”

Section: Discussionmentioning

confidence: 64%

Prostate Cancer Stem Cell-Targeted Efficacy of a New-Generation Taxoid, SBT-1214 and Novel Polyenolic Zinc-Binding Curcuminoid, CMC2.24

et al. 2013

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BackgroundProstate cancer is the second leading cause of cancer death among men. Multiple evidence suggests that a population of tumor-initiating, or cancer stem cells (CSCs) is responsible for cancer development and exceptional drug resistance, representing a highly important therapeutic target. The present study evaluated CSC-specific alterations induced by new-generation taxoid SBT-1214 and a novel polyenolic zinc-binding curcuminoid, CMC2.24, in prostate CSCs.Principal FindingsThe CD133high/CD44high phenotype was isolated from spontaneously immortalized patient-derived PPT2 cells and highly metastatic PC3MM2 cells. Weekly treatment of the NOD/SCID mice bearing PPT2- and PC3MM3-induced tumors with the SBT-1214 led to dramatic suppression of tumor growth. Four of six PPT2 and 3 of 6 PC3MM2 tumors have shown the absence of viable cells in residual tumors. In vitro, SBT-1214 (100nM-1µM; for 72 hr) induced about 60% cell death in CD133high/CD44+/high cells cultured on collagen I in stem cell medium (in contrast, the same doses of paclitaxel increased proliferation of these cells). The cytotoxic effects were increased when SBT-1214 was combined with the CMC2.24. A stem cell-specific PCR array assay revealed that this drug combination mediated massive inhibition of multiple constitutively up-regulated stem cell-related genes, including key pluripotency transcription factors. Importantly, this drug combination induced expression of p21 and p53, which were absent in CD133high/CD44high cells. Viable cells that survived this treatment regimen were no longer able to induce secondary spheroids, exhibited significant morphological abnormalities and died in 2-5 days.ConclusionsWe report here that the SBT-1214 alone, or in combination with CMC2.24, possesses significant activity against prostate CD133high/CD44+/high tumor-initiating cells. This drug combination efficiently inhibits expression of the majority of stem cell-related genes and pluripotency transcription factors. In addition, it induces a previously absent expression of p21 and p53 (“gene wake-up”), which can potentially reverse drug resistance by increasing sensitivity to anti-cancer drugs.

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Section: Discussionmentioning

confidence: 64%

Prostate Cancer Stem Cell-Targeted Efficacy of a New-Generation Taxoid, SBT-1214 and Novel Polyenolic Zinc-Binding Curcuminoid, CMC2.24

et al. 2013

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Colon cancer stem cells – From basic to clinical application

Botchkina

2013

Cancer Letters

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TBX21 predicts prognosis of patients and drives cancer stem cell maintenance via the TBX21–IL-4 pathway in lung adenocarcinoma

Zhao

Shen

et al. 2018

Stem Cell Res Ther

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BackgroundThe Th1 cell-specific transcription factor TBX21 functions as a regulator of expression of a Th1 cytokine, interferon gamma (IFN-γ). However, the specific function of TBX21 correlated with cancer stemness remains unclear.MethodsUsing univariate and multivariate survival analysis, TBX21was identified as an independent predictive factor and was associated with poor prognosis in 1389 patients with lung adenocarcinoma (LUAD). Its mechanism in the prognosis was explored by functional enrichment analysis and validated in bioexperiments.ResultsIn the training and test sets, TBX21 could classify 1389 LUAD patients into high and low-risk groups with significantly different prognosis (P < 0.01). Its prognostic power was independent of other clinical factors including stage, age, gender and smoking status. Functional studies indicated that downregulating TBX21 in lung cancer cells decreased the fraction of cancer stem cells and their sphere and tumor initiation frequency. Furthermore, the study showed that TBX21 activation transduced a TBX21–IL-4 signaling cascade to promote tumor initiation, tumor growth and expression of stemness markers.ConclusionsThese data demonstrated a key role of TBX21 in the maintenance of cancer stemness and that the TBX21–IL-4 pathway is a crucial factor contributing to lung carcinogenesis.Graphical abstractTBX21 prognostic model correlated with cancer stemness via TBX21-IL-4 pathway in LUAD patientsElectronic supplementary materialThe online version of this article (10.1186/s13287-018-0820-6) contains supplementary material, which is available to authorized users.

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Prostate and Colon Cancer Stem Cells as a Target for Anti-Cancer Drug Development

Cited by 4 publications

References 84 publications

Prostate Cancer Stem Cell-Targeted Efficacy of a New-Generation Taxoid, SBT-1214 and Novel Polyenolic Zinc-Binding Curcuminoid, CMC2.24

Prostate Cancer Stem Cell-Targeted Efficacy of a New-Generation Taxoid, SBT-1214 and Novel Polyenolic Zinc-Binding Curcuminoid, CMC2.24

Colon cancer stem cells – From basic to clinical application

TBX21 predicts prognosis of patients and drives cancer stem cell maintenance via the TBX21–IL-4 pathway in lung adenocarcinoma

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