Stem Cell Models for Breast and Colon Cancer: Experimental Approach for Drug Discovery

Abstract

The progression of the early stages of female breast and colon cancer to metastatic disease represents a major cause of mortality in women. Multi-drug chemotherapy and/or pathway selective targeted therapy are notable for their off-target effects and are associated with spontaneous and/or acquired chemotherapy resistance and the emergence of premalignant chemo-resistant cancer-initiating stem cells. The stem cell populations are responsible for the evolution of therapy-resistant metastatic disease. These limitations emphasize an unmet need to develop reliable drug-resistant cancer stem cell models as novel experimental approaches for therapeutic alternatives in drug discovery platforms. Drug-resistant stem cell models for breast and colon cancer subtypes exhibit progressive growth in the presence of cytotoxic chemo-endocrine therapeutics. The resistant cells exhibit upregulated expressions of stem cell-selective cellular and molecular markers. Dietary phytochemicals, nutritional herbs and their constituent bioactive compounds have documented growth inhibitory efficacy for cancer stem cells. The mechanistic leads for the stem cell-targeted efficacy of naturally occurring agents validates the present experimental approaches for new drug discovery as therapeutic alternatives for therapy-resistant breast and colon cancer. The present review provides a systematic discussion of published evidence on (i) conventional/targeted therapy for breast and colon cancer, (ii) cellular and molecular characterization of stem cell models and (iii) validation of the stem cell models as an experimental approach for novel drug discovery of therapeutic alternatives for therapy-resistant cancers.

Kurarinone targets JAK2‐STAT3 signaling in colon cancer‐stem‐like cells

“…The results are in consistent with previous published reports. 3,4 Our experimental analysis showed that KU treatment significantly reduced the sphere formation in HCT-116 cells and decreased the expression of CD44, c-Myc, Sox2, and Bmi1 markers at mRNA and protein levels. These results suggest that KU treatment has potential to inhibit colon cancer progression by reducing sphere formation in these cells.…”

“…2 Pharmacological agents targeting colon cancer cells are known to produce off-target effects, and acquired therapy resistance which leads to the initiation of colon cancer stem-like cells (CCSCs) population. 3 CCSCs are slow-dividing cells, known to play a critical role in cancer progression, recurrence, and metastasis. Standard chemotherapeutic drugs target fast-dividing cancer cells.…”

“…CCSCs express characteristic membrane-bound markers such as CD44, SOX2, and c-Myc providing stemness and selfrenewal properties in these special types of cells. 3,4 Dysregulated cellular signaling pathways results in the growth, metastasis, and stem cell formation in colon cancer. The JAK/STAT proteins are receptor tyrosine kinases and forms key component of the JAK/STAT pathway.…”

Increased soluble E‑cadherin of spheroid formation supplemented with fetal bovine serum in colorectal cancer cells

“…Although the CSC markers between cancers are not identical (10), CSCs exhibit common characteristics regarding the maintenance of CSC pool, tumorigenesis, metastasis, and treatment resistance and recurrence (11)(12)(13). As p21 attenuates Ras-and c-Myc-dependent EMT and CSC-like gene expression in vivo (14), it suppresses the cell cycle and is also used as a biomarker for CSCs (15).…”

“…Similarly, the Wnt/β-catenin signaling pathway is critical for the regulation of cell proliferation, differentiation and apoptosis during regeneration ( 16 ). CSCs are typically determined by the cell surface proteins [cluster of differentiation (CD) 44, and nuclear transcription factors, octamer binding transcription factor-4 (Oct-4), and sex determining region Y-box-2 (Sox-2)] ( 13 , 17 ) as well as ATP-binding cassette super-family G member 2 (ABCG2) transporter ( 18 ). Moreover, non-CSCs can acquire a CSC-like phenotype during EMT ( 19 ), and EMT-induced cells can form spheres in an anchorage-independent growth environment ( 20 ).…”