The Chemo-Sensitisation Effect Of Curcumin Against Low Dose Cisplatin On Non-Small Cell Lung Cancer (NSCLC) Stem Cells

Cancer stem cells (CSCs) represent a small subpopulation within a tumour that possesses the stem-like properties but are also initiating resistance towards cytotoxic agent which contribute to cancer relapse. A natural compound such as curcumin that contains high polyphenol has been found to possess chemo-sensitivity effect with an ability to sensitise the CSCs to the cytotoxic agents such as cisplatin. Therefore, the present study was designed to investigate the efficiency of curcumin as a chemo-sensitiser in lung CSCs and to analyse its inhibitory effect on CSCs activity using A549 and H2170 cell lines that belong to non-small cell lung cancer (NSCLC)

The Chemo-Sensitisation Effect Of Curcumin Against Low Dose Cisplatin On Non-Small Cell Lung Cancer (Nsclc) Stem Cells

Cancer stem cells (CSCs) represent a small subpopulation within a tumour that possesses the stem-like properties but are also initiating resistance towards cytotoxic agent which contribute to cancer relapse. A natural compound such as curcumin that contains high polyphenol has been found to possess chemo-sensitivity effect with an ability to sensitise the CSCs to the cytotoxic agents such as cisplatin. Therefore, the present study was designed to investigate the efficiency of curcumin as a chemo-sensitiser in lung CSCs and to analyse its inhibitory effect on CSCs activity using A549 and H2170 cell lines that belong to non-small cell lung cancer (NSCLC). The NSCLC cell lines cultures were treated with various concentrations of cisplatin and curcumin to obtain the inhibitory concentration (IC50) using 3-(4, 5-dimethylthiazol-2-yl)-2H-tetrazolium, inner salt (MTS) assay. The lung CSCs with phenotype CD166+EpCAM+ was isolated using fluorescence-activated cell sorting (FACS). The efficiency of curcumin to sensitise lung CSCs was observed on apoptosis and stemness characteristics including migration ability, colonies and spheroid formation. The mRNA level was analysed for genes involved in apoptosis and stemness using quantitative real time-polymerase chain reaction (RT-qPCR). Liquid chromatography mass spectrometry (LCMS) was used to evaluate the effect of curcumin on CSC niche. The results discovered that exposure of NSCLC cell lines to curcumin (10 μM – 40 μM) reduced the percentage of cells viability to an average of ~51% and ~54% in both A549 and H2170

Targeting Lung Cancer Stem Cells: Research and Clinical Impacts

Lung cancer is the most common cancer worldwide, accounting for 1.8 million new cases and 1.6 million deaths in 2012. Non-small cell lung cancer (NSCLC), which is one of two types of lung cancer, accounts for 85–90% of all lung cancers. Despite advances in therapy, lung cancer still remains a leading cause of death. Cancer relapse and dissemination after treatment indicates the existence of a niche of cancer cells that are not fully eradicated by current therapies. These chemoresistant populations of cancer cells are called cancer stem cells (CSCs) because they possess the self-renewal and differentiation capabilities similar to those of normal stem cells. Targeting the niche of CSCs in combination with chemotherapy might provide a promising strategy to eradicate these cells. Thus, understanding the characteristics of CSCs has become a focus of studies of NSCLC therapies

Synergistic Roles of Curcumin in Sensitising the Cisplatin Effect on a Cancer Stem Cell-Like Population Derived from Non-Small Cell Lung Cancer Cell Lines

Cancer stem cells (CSCs) represent a small subpopulation within a tumour. These cells possess stem cell-like properties but also initiate resistance to cytotoxic agents, which contributes to cancer relapse. Natural compounds such as curcumin that contain high amounts of polyphenols can have a chemosensitivity effect that sensitises CSCs to cytotoxic agents such as cisplatin. This study was designed to investigate the efficacy of curcumin as a chemo-sensitiser in CSCs subpopulation of non-small cell lung cancer (NSCLC) using the lung cancer adenocarcinoma human alveolar basal epithelial cells A549 and H2170. The ability of curcumin to sensitise lung CSCs to cisplatin was determined by evaluating stemness characteristics, including proliferation activity, colony formation, and spheroid formation of cells treated with curcumin alone, cisplatin alone, or the combination of both at 24, 48, and 72 h. The mRNA level of genes involved in stemness was analysed using quantitative real-time polymerase chain reaction. Liquid chromatography-mass spectrometry was used to evaluate the effect of curcumin on the CSC niche. A combined treatment of A549 subpopulations with curcumin reduced cellular proliferation activity at all time points. Curcumin significantly (p SOX2, NANOG, and KLF4. Curcumin also regulated the niche of CSCs by inhibiting chemoresistance proteins, aldehyde dehydrogenase, metastasis, angiogenesis, and proliferation of cancer-related proteins. These results show the potential of using curcumin as a therapeutic approach for targeting CSC subpopulations in non-small cell lung cancer

Novel triple-positive markers identified in human non-small cell lung cancer cell line with chemotherapy-resistant and putative cancer stem cell characteristics

Through the specific identification and direct targeting of cancer stem cells (CSCs), it is believed that a better treatment efficacy of cancer may be achieved. Hence, the present study aimed to identify a CSC subpopulation from adenocarcinoma cells (A549) as a model of non-small cell lung cancer (NSCLC). Initially, we sorted two subpopulations known as the triple-positive (EpCAM+/CD166+/CD44+) and triple-negative (EpCAM−/CD166−/CD44−) subpopulation using fluorescence-activated cell sorting (FACS). Sorted cells were subsequently evaluated for proliferation and chemotherapy-resistance using a viability assay and were further characterized for their clonal heterogeneity, self-renewal characteristics, cellular migration, alkaline dehydrogenase (ALDH) activity and the expression of stemness-related genes. According to our findings the triple-positive subpopulation revealed significantly higher (P<0.01) proliferation activity, exhibited better clonogenicity, was mostly comprised of holoclones and had markedly bigger (P<0.001) spheroid formation indicating a better self-renewal capacity. A relatively higher resistance to both 5-fluouracil and cisplatin with 80% expression of ALDH was observed in the triple-positive subpopulation, compared to only 67% detected in the triple-negative subpopulation indicated that high ALDH activity contributed to greater chemotherapy-resistance characteristics. Higher percentage of migrated cells was observed in the triple-positive subpopulation with 56% cellular migration being detected, compared to only 19% in the triple-negative subpopulation on day 2. This was similarly observed on day 3 in the triple-positive subpopulation with 36% higher cellular migration compared to the triple-negative subpopulation. Consistently, elevated levels of the stem cell genes such as REX1 and SSEA4 were also found in the triple-positive subpopulation indicating that the subpopulation displayed a strong characteristic of pluripotency. In conclusion, our study revealed that the triple-positive subpopulation demonstrated similar characteristics to CSCs compared to the triple-negative subpopulation. It also confirmed the feasibility of using the triple-positive (EpCAM+/CD166+/CD44+) marker as a novel candidate marker that may lead to the development of novel therapies targeting CSCs of NSCLC