Abstract
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 < 0.001) suppressed colonies formation by 50% and shrank the spheroids in CSC subpopulations, indicating inhibition of their self-renewal capability. This effect also was manifested by the down-regulation of 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.
Highlights
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer as it accounts for approximately 80–85% of all lung cancer cases, with the remainder being small cell lung cancer (SCLC) [1,2,3,4]
Our previous study has shown that curcumin was able to increase the efficacy of cisplatin by enhancing the cisplatin-induced metastatic inhibition and apoptosis of the highly migratory cancer stem cells (CSCs) subpopulation of NSCLC cell lines
As reported in our previous study [15], the combination of 41 μM curcumin and 30 μM cisplatin was selected for A549 cells, and 33 μM of curcumin and 7 μM of cisplatin were selected for H2170 cells for further downstream study
Summary
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer as it accounts for approximately 80–85% of all lung cancer cases, with the remainder being small cell lung cancer (SCLC) [1,2,3,4] Conventional treatments such as radiotherapy, chemotherapy, and surgery are common cancer therapy methods, but they often lead to tumour recurrence. CSCs sheltered within the cancerous microenvironment, called the niche This niche helps them retain their self-renew ability and propagate more differentiated progenitor cells while staying undifferentiated state [10,11]. Recent studies have suggested that natural polyphenols might be used to sensitise tumour cells to chemotherapy and radiotherapy by inhibiting the pathway that leads to treatment resistance. The identification of proteins that regulate the CSC niche of NSCLC would open up future targeted therapy for lung cancer
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