Abstract
Combination therapy comprising natural polyphenols and anticancer drugs has been used to decrease the adverse effects and increase the effectiveness and antioxidant activities of the drugs. The antioxidant and anticancer effects of quercetin (Q), a nutritive polyphenol, have been observed both in vitro and in vivo. Likewise, the anticancer activity of sulfamethoxazole (S) has been demonstrated in vitro and in vivo. This study aimed to investigate the in vitro and in vivo anticancer effects of Q alone and in combination with S. The in vitro effects of S, Q, and S + Q on HCT-116, HepG2, MCF-7, and PC3 cell lines were examined. Additionally, the in vivo effects of these drugs were evaluated using Ehrlich ascites carcinoma (EAC) tumor-bearing mice. The in vitro data revealed the potent anticancer activity of S + Q through the induction of apoptosis and cell cycle arrest. The EAC-inoculated mice treated with S + Q presented with elevated SOD, GSH, CAT, and TAC levels and decreased malondialdehyde levels compared with the untreated EAC group, thus revealing the antioxidant and protective actions of S + Q against EAC cell invasion. Furthermore, the downregulation of NFkB and upregulation of the caspase3 gene in the EAC-inoculated mice treated with the S + Q indicated the induction of the apoptotic pathway and decrease in both cell proliferation and metastasis. In conclusion, the combination of S and Q might exert anticancer effects by inducing apoptosis and exhibiting selective toxicity against the cancer cells and thereby protecting the vital organs.
Highlights
Anticancer, chemotherapeutic, and radio-therapeutic treatments are associated with several drawbacks
Recent studies approved the in vivo anticancer effects of S + selenium on hepatocellular carcinoma (Gupta et al 2013) and its improved in vitro anticancer activity against colon carcinoma (HCT-116) and human metastatic breast cancer (MDA-MB–231) cells when combined with copper (RAMA and SELVAMEENA 2015)
These results demonstrate the synergistic effect of Q and S as anti-proliferative and anticancer agents
Summary
Anticancer, chemotherapeutic, and radio-therapeutic treatments are associated with several drawbacks. Sulfa-drugs or sulfonamides are a group of biologically active compounds with flexible structures, which allow them to possess a broad range of biological activities, such as anti-inflammatory (Sondhi et al 2000; El-Araby et al 2012), antibacterial (Wulf and Matuszewski 2013), antitumor (Ghorab et al 2009, 2010), protease inhibitor (Stranix et al 2006), and carbonic anhydrase inhibitory activities (Casini et al 2002; Scozzafava et al 2003; Ghorab et al 2009; Marques et al 2010). Sulfa-drugs gained a fast approval to be used as anticancer agents in patients with solid tumors (Raymond et al 2002; Terret et al 2003) because it has been used as antibacterial agents for centuries (Greenwood 2010). Recent studies approved the in vivo anticancer effects of S + selenium on hepatocellular carcinoma (Gupta et al 2013) and its improved in vitro anticancer activity against colon carcinoma (HCT-116) and human metastatic breast cancer (MDA-MB–231) cells when combined with copper (RAMA and SELVAMEENA 2015)
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