Abstract
Curcumin is a novel drug for lung cancer treatment. However, the mechanism underlying the anti-tumor effect of curcumin remains elusive. Previous evidences indicated that, the methylating transferase DNMT1 is downregulated by curcumin, and the transcription factor 21 (TCF21) is suppressed by DNMT1. We hereby attempt to elucidate the correlation between curcumin treatment and TCF21 expression. Exosomes derived from curcumin-pretreated H1299 cells were used to treat BEAS-2B cells, which induced proliferation, colony formation and migration of BEAS-2B cells. An increase in TCF21 expression in response to curcumin was also seen, as revealed by real-time PCR (RT-PCR) and western blot. Analysis using the GEO database (access #GSE21210) indicated that a positive correlation existed between TCF21 levels and lung cancer patient survival. TCF21 overexpression and knockdown was introduced to H1299 cells through lentiviral system, which led to suppression and promotion of tumor growth, respectively. We also demonstrated that DNMT1 expression was downregulated by curcumin. Therefore, curcumin exerts its anti-cancer function by downregulating DNMT1, thereby upregulating TCF21.
Highlights
Lung cancer is the leading cause of cancer-related death worldwide and constitutes a major public health problem [1]
We examined the correlation between exosomal transcription factor 21 (TCF21) levels and curcumin
real-time PCR (RT-PCR) analysis indicated that downregulation of TCF21 was a characteristic of aggressive lung cancer, and the TCF21 levels were inversely correlated with the aggressiveness of cancer cells (Figure 2A)
Summary
Lung cancer is the leading cause of cancer-related death worldwide and constitutes a major public health problem [1]. Effective therapy against lung cancer is of paramount importance to improve prognosis and survival of lung cancer patients. Resistance to existing chemotherapy drugs poses a serious challenge to lung cancer therapy, necessitating the development of new drugs against lung cancer. A number of plant-derived anti-cancer compounds have been discovered [2]. One of them is curcumin, known as diferuloylmethane, which is a phenolic compound isolated from Curcuma longa [3, 4]. Curcumin is well tolerated in high doses, and has been found to exert antiinflammatory and anti-oxidative effects. The precise mechanism underlying the action of this drug in cancer is still unclear
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