Cancer anti-inflammatory, antiulcer, antiviral, and anti-microbial activities (Cusk et

Cancer is one of the major health problems all over the world. In 2015, over 8.7 million patients died from cancer globally, with approximately 17.5 million new cases (Fitzmaurice et al., 2017). Despite extensive efforts over the last several decades, cancer is still the second most common cause of death in many countries after cardiovascular diseases (Ma and Yu, 2006). By 2030, the annual number of new cancer cases is estimated to be 26 million, with 17 million cancer deaths (Thun et al., 2009). Due to this global increase in the cancer burden, a massive research effort has been devoted to the discovery of potent and selective anticancer agents (Goldblatt and Lee, 2010; Karabacak et al., 2015). 

Over the past few years protein kinases have become the most important group of drug target in anticancer drug discovery which play a major role in signal transduction and other cellular activation processes (Perez et al., 2011; Wang and Cole, 2014). More than 25 kinase inhibitors have been approved for cancer treatment and several promising candidates are currently in clinical development after the milestone approval of imatinib, the first inhibitor of tyrosine kinase that binds to kinase domain of Bcr-Abl observed in 95% of CML patients (Gross et al., 2015; Altintop et al, 2018). While imatinib can be initially effective in treating CML, some patients have shown drug resistance to imatinib due to the development of point mutations (Soverini et al., 2011). This major limitation is becoming a significant concern for the treatment of imatinib-resistant CML (Barouch-bentov, 2012). Several new generation drugs have been developed, but there are still no alternative drugs available to overcome this problem (Weisberg et al., 2007; Giles et al., 2009).

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Pentacyclic triterpenoids have emerged as a unique class of natural compounds and have been studied extensively for more than a century due to their effective therapeutic applications for the treatment of a wide spectrum of diseases and its high safety profile (Radwan et al., 2016; Salvador et al., 2017; Ciftci et al., 2018). Glycyrrhetic acid is a natural pentacyclic triterpenoid extracted from liquorice, which has various biological activities such as anticancer, anti-inflammatory, antiulcer, antiviral, and anti-microbial activities (Cusk et al., 2010). Recent studies have indicated that GA has a potent antitumor activity against different cancer cell lines including human ovarian cancer, breast cancer, hepatocellular carcinoma, pituitary adenoma, human bladder, and non-small cell lung cancer (Sharma et al., 2012; Zhu et al., 2015). In this study, we investigated in vitro biological activities of GA against HeLa and 3 different leukemic cell lines (Jurkat, MT-2 and K562) and then focused on its anti-tyrosine kinase activity. Furthermore, tumor selectivity test on normal blood cells (PBMC), the apoptotic/necrotic analysis against K562 cell line and molecular docking with the kinase domain were carried out using GA.