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Review
. 2022 Aug 17;23(16):9223.
doi: 10.3390/ijms23169223.

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

Nitin T Telang  1
Affiliations
Review

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

Nitin T Telang. Int J Mol Sci. .

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.

Keywords: breast and colon cancer; cancer stem cells; therapeutic alternatives.

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Conflict of interest statement

The author declares no conflict of interest.

Figures

Figure 1
Figure 1
Growth inhibitory effects of pharmacological agents on colon cancer models. (A) Reduction in AI colony number by treatment with DFMO, CLX, 5-FU and SUL in the FAP model for colon cancer. EtOH versus DFMO and CLX p = 0.038; EtOH versus 5-FU and SUL p = 0.04. (B) Reduction in AI colony number by treatment with SUL, DFMO and 5-FU in the HNPCC model. EtOH versus SUL and DFMO p = 0.037; EtOH versus 5-FU p = 0.04. Data analyzed by ANOVA with Dunnett’s multiple comparison post-hoc test. AI, anchorage independent; EtOH, ethanol; DFMO, difluoro-methyl ornithine; CLX, celecoxib; 5-FU, 5-fluoro-uracil; SUL, sulindac.
Figure 1
Figure 1
Growth inhibitory effects of pharmacological agents on colon cancer models. (A) Reduction in AI colony number by treatment with DFMO, CLX, 5-FU and SUL in the FAP model for colon cancer. EtOH versus DFMO and CLX p = 0.038; EtOH versus 5-FU and SUL p = 0.04. (B) Reduction in AI colony number by treatment with SUL, DFMO and 5-FU in the HNPCC model. EtOH versus SUL and DFMO p = 0.037; EtOH versus 5-FU p = 0.04. Data analyzed by ANOVA with Dunnett’s multiple comparison post-hoc test. AI, anchorage independent; EtOH, ethanol; DFMO, difluoro-methyl ornithine; CLX, celecoxib; 5-FU, 5-fluoro-uracil; SUL, sulindac.
Figure 2
Figure 2
Isolation of drug-resistant putative stem cells in breast cancer models. (A) Decreased viable cell number by treatment with TAM in TAM-S cells. EtOH versus TAM p = 0.01. (B) Increased tumor spheroid number in TAM-R cells. TAM-S versus TAM-R p = 0.01. (C) Decreased viable cell number by treatment with DOX in DOX-S cells. EtOH versus DOX p = 0.01. (D) Increased tumor spheroid number in DOX-R cells. DOX-S versus DOX-R p = 0.01. Data analyzed by the two-way Student’s t test. TAM, tamoxifen; TAM-S, TAM sensitive; TAM-R, TAM resistant; EtOH, ethanol; DOX, doxorubicin; DOX-S, DOX sensitive; DOX-R, DOX resistant (data summarized from [35,37]).
Figure 2
Figure 2
Isolation of drug-resistant putative stem cells in breast cancer models. (A) Decreased viable cell number by treatment with TAM in TAM-S cells. EtOH versus TAM p = 0.01. (B) Increased tumor spheroid number in TAM-R cells. TAM-S versus TAM-R p = 0.01. (C) Decreased viable cell number by treatment with DOX in DOX-S cells. EtOH versus DOX p = 0.01. (D) Increased tumor spheroid number in DOX-R cells. DOX-S versus DOX-R p = 0.01. Data analyzed by the two-way Student’s t test. TAM, tamoxifen; TAM-S, TAM sensitive; TAM-R, TAM resistant; EtOH, ethanol; DOX, doxorubicin; DOX-S, DOX sensitive; DOX-R, DOX resistant (data summarized from [35,37]).
Figure 2
Figure 2
Isolation of drug-resistant putative stem cells in breast cancer models. (A) Decreased viable cell number by treatment with TAM in TAM-S cells. EtOH versus TAM p = 0.01. (B) Increased tumor spheroid number in TAM-R cells. TAM-S versus TAM-R p = 0.01. (C) Decreased viable cell number by treatment with DOX in DOX-S cells. EtOH versus DOX p = 0.01. (D) Increased tumor spheroid number in DOX-R cells. DOX-S versus DOX-R p = 0.01. Data analyzed by the two-way Student’s t test. TAM, tamoxifen; TAM-S, TAM sensitive; TAM-R, TAM resistant; EtOH, ethanol; DOX, doxorubicin; DOX-S, DOX sensitive; DOX-R, DOX resistant (data summarized from [35,37]).
Figure 3
Figure 3
Isolation of drug-resistant putative stem cells in colon cancer models. (A) Deceased viable cell number by treatment with SUL in SUL-S cells. EtOH versus SUL p = 0.01. (B) Increased tumor spheroid number by treatment with SUL in SUL-R cells. SUL-S versus SUL-R p = 0.01. (C) Decreased viable cell number by treatment with 5-FU in 5-FU-S cells. EtOH versus 5-FU p = 0.01. (D) Increased tumor spheroid number by treatment in 5-FU-R cells5-FU-S versus 5-FU-R p = 0.01. SUL, sulindac; SUL-S, SUL sensitive; SUL-R, SUL resistant; 5-FU, 5-fluoro-uracil; 5-FU-S, 5-FU sensitive; 5-FU-R, 5-FU resistant (Data summarized from [36,37]).
Figure 3
Figure 3
Isolation of drug-resistant putative stem cells in colon cancer models. (A) Deceased viable cell number by treatment with SUL in SUL-S cells. EtOH versus SUL p = 0.01. (B) Increased tumor spheroid number by treatment with SUL in SUL-R cells. SUL-S versus SUL-R p = 0.01. (C) Decreased viable cell number by treatment with 5-FU in 5-FU-S cells. EtOH versus 5-FU p = 0.01. (D) Increased tumor spheroid number by treatment in 5-FU-R cells5-FU-S versus 5-FU-R p = 0.01. SUL, sulindac; SUL-S, SUL sensitive; SUL-R, SUL resistant; 5-FU, 5-fluoro-uracil; 5-FU-S, 5-FU sensitive; 5-FU-R, 5-FU resistant (Data summarized from [36,37]).
Figure 3
Figure 3
Isolation of drug-resistant putative stem cells in colon cancer models. (A) Deceased viable cell number by treatment with SUL in SUL-S cells. EtOH versus SUL p = 0.01. (B) Increased tumor spheroid number by treatment with SUL in SUL-R cells. SUL-S versus SUL-R p = 0.01. (C) Decreased viable cell number by treatment with 5-FU in 5-FU-S cells. EtOH versus 5-FU p = 0.01. (D) Increased tumor spheroid number by treatment in 5-FU-R cells5-FU-S versus 5-FU-R p = 0.01. SUL, sulindac; SUL-S, SUL sensitive; SUL-R, SUL resistant; 5-FU, 5-fluoro-uracil; 5-FU-S, 5-FU sensitive; 5-FU-R, 5-FU resistant (Data summarized from [36,37]).
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