Abstract
Resveratrol is a phytoalexin that naturally occurs in grapes, blueberries, cranberries, peanuts and many other plants. Although resveratrol inhibits carcinogenesis in all three stages, its clinical application is restricted due to poor pharmacokinetics. The methylated analogues of resveratrol have been found to have higher bioavailability and cytotoxic activity than that of the prototupe compound. Among the various methoxy derivatives of resveratrol, 3,4,5,4′-tetrametoxystilbene (DMU-212) is suggested to be one of the strongest activators of cytotoxicity and apoptosis. DMU-212 has been shown to exert anti-tumor activity in DLD-1 and LOVO colon cancer cells. Since colorectal cancer is the third most common cause of cancer-related deaths worldwide, the development of new anticancer agents is nowadays of high significance. The aim of the present study was to assess the anticancer activity of 4′-hydroxy-3,4,5-trimetoxystilbene (DMU-281), the metabolite of DMU-212, in DLD-1 and LOVO cell lines. We showed for the first time the cytotoxic activity of DMU-281 triggered via cell cycle arrest at G2/M phase and apoptosis induction accompanied by the activation of caspases-9, -8, -3/7. Furthermore, DMU-281 has been found to change the expression pattern of genes and proteins related to intrinsic as well as extrinsic apoptosis. Since the activation of these pathways of apoptosis is still the most desired strategy in anticancer research, DMU-281 seems to provide a promising approach to the treatment of colon cancer.
Highlights
According to the WHO, cancer is the most common cause of death globally and led to ~9.6 million deaths in 2018
To investigate the cytotoxic effects of the four metabolites in DLD-1, LOVO and CaCo-2 colon cancer cells, an MTT assay was performed after 24 h, 48 h and 72 h at concentration ranges of 0–20 μM
The viability of the DLD-1, LOVO and the CaCo-2 cells treated with the highest concentration 20 μM of DMU-281 for 72 h was reduced to 44.87% ± 7.57%, 50.71% ± 14.94% and 84.87% ± 11.56%, respectively (Table 1)
Summary
According to the WHO, cancer is the most common cause of death globally and led to ~9.6 million deaths in 2018. About one in six deaths have been estimated to occur due to cancer itself. Colorectal cancer is the third major cause of cancer-related deaths worldwide (862,000 deaths in 2018) [1]. The high mortality of this tumor is mainly due to the late diagnosis at stages III and IV and impaired clinical responses to chemotherapy due to emerging drug resistance [2]. The development of new anti-cancer agents is nowadays of high significance. One of the most desired types of cancer cell death triggered by chemotherapeutics is apoptosis since it has been shown not to induce any inflammation in the aftermath of cancer treatment [3,4]
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