Modulatory effect of hesperidin on benzo(a)pyrene induced experimental lung carcinogenesis with reference to COX-2, MMP-2 and MMP-9

Department of Biochemistry, University of Madras, Chennai 600 025, India.
European journal of pharmacology (Impact Factor: 2.53). 09/2010; 649(1-3):320-7. DOI: 10.1016/j.ejphar.2010.09.017
Source: PubMed


Hesperidin is a naturally occurring flavonoid that has been reported to possess anticancer effects. The purpose of this study is to evaluate the effect of hesperidin in modulating the expressions of cyclooxygenase-2 (COX-2), mast cells (MCs) and matrix metalloproteinases (MMPs) during benzo(a)pyrene (B(a)P) induced lung carcinogenesis in mice. B(a)P (50 mg/kg body weight) induced animals showed increased mast cell density (MCD) as revealed by toluidine blue staining and severe expression of COX-2 along with upregulated expression of MMP-2 and MMP-9 as revealed by Western blotting and immunohistochemistry. Supplementation of hesperidin (25 mg/kg body weight) to lung cancer bearing mice attenuated MCD and downregulated the expressions of COX-2, MMP-2 and MMP-9. These observations show that hesperidin exerts its anti-carcinogenic activity against lung cancer by altering the expressions of COX-2, MMP-2 and MMP-9.

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Available from: Ramakrishnan Gopalakrishnan, Mar 21, 2014
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    • "In recent years, studies have focused mainly on the protective properties of Hsd and Hst against various oxidants , such as peroxynitrite and hydrogen peroxide, and several other chemicals and toxins that cause damage to tissues via oxidative stress or other mechanisms (Kalpana et al., 2009; Kamaraj et al., 2010; Shrivastava et al., 2013; Kawaguchi et al., 2004; Kim et al., 2004) In 2009, Kalpana et al. (2009) studied different aspects of antioxidant and protective effects of Hsd against H 2 O 2 -induced membrane damage in red blood cells (RBCs). They found that Hsd had significant radical scavenging activity and prevented H 2 O 2 -induced oxidative damage on the cellular membranes of RBCs. "
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    • "While B(a)P lung carcinogenesis caused an increase in the mast cell density (MCD), COX-2, MMP-2 and matrix metalloproteinase-9 (MMP-9) expression, Hsd could decrease MCD, which was most likely due to a reduction in the COX-2 expression, thus reducing the chance of angiogenesis and invasion. MMPs have been shown to be tightly related to angiogenesis, invasion and metastasis , and here, the Hsd treatment significantly reduced the MMP-2 and MMP-9 expression [39]. "
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    • "Laboratory studies have showed that citrus flavonoids and anthocyanins are able to inhibit the growth of several tumors, including breast and colorectal cancer [46,47] through inhibiting multiple cancer-related biological pathways, such as carcinogen bio-activation, cell-signaling, cell cycle regulation, angiogenesis, and inflammation [48,49]. Citrus flavonoids have been hypothesized to inhibit the matrix metalloproteinase (MMP) secretion, migration, invasion and adhesion [50-52], and to have pro-apoptotic activity [53-56]. "
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