Esculetin (6,7-dihydroxycoumarin): A potential cancer chemopreventive agent through suppression of Sp1 in oral squamous cancer cells

Abstract

Esculetin (6,7-dihydroxycoumarin), a coumarin compound, is known to inhibit proliferation and induce apoptosis in several types of human cancer cells and is regarded as a promising chemotherapeutic agent. The purpose of the present study was to investigate the anti-proliferative effects of esculetin on two oral squamous cell carcinoma (OSCC) cell lines, HN22 and HSC4, through regulation of specificity protein 1 (Sp1). We examined the apoptotic effects of esculetin were measured by MTS assay, DAPI staining, Annexin V, PI staining, RT-PCR, western blot analysis and immunocytochemistry in HN22 and HSC4 cells. Taken together, the results of the present study indicate that esculetin had anti-proliferative effect on the growth of OSCC cells (HN22 and HSC4) in a dose- and time-dependent manner. The treatment of HN22 and HSC4 cells with esculetin led to a significant reduction in growth and induced apoptosis, followed by the regulation of Sp1 and Sp1 regulatory protein. This indicates that esculetin inhibited cell growth and induced apoptosis by suppressing Sp1 in HN22 and HSC4 cells, suggesting it to be a potent anticancer drug candidate for oral cancer.

Esculetin induces cell cycle arrest and apoptosis in human colon cancer LoVo cells

“…In addition, there are several studies that suggest that ESC induces cell cycle arrest in cancer cells. In oral squamous cancer cells, ESC induced increased expression of p27 and p21 and decreased expression of cyclin D1, as well as induced G0/G1 arrest . In human oral cancer SAS cells, ESC induced G2 phase arrest and in liver cancer SMC7721 cells, ESC induced S phase arrest .…”

“…However, when the damage is severe, the cells express the Bax gene by p53 and induce apoptosis . Recent studies have shown that ESC induced cell cycle arrest at the G1 phase and increased p53, p21, and Bax in oral squamous cancer HN22 and HSC4 cells . In addition, there are several studies that suggest that ESC induces cell cycle arrest in cancer cells.…”

“…Sp1 is overexpressed in various human cancer cell lines and many studies have reported that Sp1 is highly expressed in a variety of cancers such as breast, prostate, pancreas, lung, and colon cancers . Several studies have shown that ESC induces a reduction in the Sp1 expression level in cancer cells such as oral squamous cancer cells and human malignant melanoma . To determine whether the level of Sp1 expression would be reduced by ESC, human colon cancer LoVo cells were treated with various concentrations (200, 400, and 600 μM) of ESC for 24 hours.…”

“…ESC is found in many medicinal plants, such as Artemisia capillaries , Citrus limonia , and Euphorbia lathyris . ESC has been reported to exhibit a wide range of biological and pharmacological properties including anti‐inflammatory, anti‐oxidant, anti‐edema, and anti‐tumor promoting properties . In addition, many previous studies have reported that ESC induces apoptosis in various cancer cells such as oral cancer, skin cancer, lung cancer, and gastric cancer .…”

Insulin sensitizing and cardioprotective effects of Esculetin and Telmisartan combination by attenuating Ang II mediated vascular reactivity and cardiac fibrosis

“…In addition, esculetin did not have any mutagenic or genotoxic effect in cultured human lymphocytes (Maistro et al, 2015). Esculetin also shows a potential therapeutic role in cancer (Cho et al, 2015), obesity (Kim and Lee, 2015;Sim et al, 2015), and diabetes (Surse et al, 2011). Recently, we have reported that Esculetin shows cardioprotective effect by reversing post translational histone modifications associated with IR and type 2 diabetes (Kadakol et al, 2015b).…”