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.

Download full-text


Available from: Ramakrishnan Gopalakrishnan, Mar 21, 2014
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Inflammation and oxidative stress are two major causes of various life-threatening diseases. Hesperidin (Hsd) and its aglycone, hesperetin (Hst), are two flavonoids from citrus species that have numerous biological properties, particularly antioxidant and anti-inflammatory. New findings showed that the antioxidant activity of Hsd/Hst was not only limited to its radical scavenging activity, but it augmented the antioxidant cellular defenses via the ERK/Nrf2 signaling pathway as well. Various in vitro and in vivo studies have been conducted to evaluate Hsd, its metabolites, or its synthetic derivatives at reducing inflammatory targets including NF-κB, iNOS, and COX-2, and the markers of chronic inflammation. In this review, new findings regarding the molecular targets of Hsd and Hst in the reduction of oxidative stress are discussed. Also, in the anti-inflammatory section, we provide a summary of significant investigations concerning the mechanisms of action based on the studied inflammation models. Copyright © 2014 John Wiley & Sons, Ltd.
    Full-text · Article · Mar 2015 · Phytotherapy Research
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hesperidin (Hsd) and its aglycone, hesperetin (Hst), are two flavonoids from citrus species that have various biological properties, particularly those for the prevention of cancer and cardiovascular diseases. Studies have shown both anti-cancer and cancer chemopreventive effects for Hsd and Hst. Cancer chemopreventive properties of Hsd and Hst are mainly associated with their antioxidant, radical scavenging and anti-inflammatory activities. In addition, Hsd and Hst interfere at different stages of cancer. Unlike conventional anti-cancer drugs, Hsd and Hst inhibit tumor growth by targeting multiple cellular protein targets at the same time, including caspases, Bcl-2 (B-cell lymphoma 2) and Bax (Bcl-2 associated X protein) for the induction of apoptosis, and COX-2 (cyclooxygenase-2), MMP-2 (matrix metalloproteinase-2) and MMP-9 for the inhibition of angiogenesis and metastasis. The results of the recent basic and clinical studies revealed the beneficial effects for Hst, Hsd and their derivatives in the treatment of heart failure and cardiac remodeling, myocardial ischemia and infarction, and hypertension. In addition, the valuable effects of Hst and Hsd in the treatment of diabetes and dyslipidemia with their anti-platelet and anti-coagulant effects make them good candidates in the treatment of various cardiovascular diseases. In this review, new findings regarding the molecular targets of Hsd and Hst, animal studies and clinical trials are discussed. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Jan 2015 · Life Sciences
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Populations living in the area of the Mediterranean Sea suffered by decreased incidence of cancer compared with those living in the regions of northern Europe and US countries, attributed to healthier dietary habits. Nowadays, we are assisting to a moving away from the traditional Mediterranean dietary pattern, but whether this changing is influencing risk of cancers is still unclear. The aim of the study was to review recent evidence on potential relationship between the adherence to the Mediterranean diet and cancer. Discussion The most recent pooled analyses of epidemiological studies supported strongly the hypothesis that the Mediterranean diet may play a role in preventing several types of cancers, especially those of digestive tract, whereas contrasting results were reported for hormone-dependent cancers. Specific aspects of the Mediterranean diet such as high fruit and vegetables and low red processed meat intake may explain such protective effects. Moreover, evidence regarding olive oil and whole grains increase the beneficial effects of such dietary pattern against cancer. Conclusions Literature evidence actually demonstrates that the increased adherence to the Mediterranean dietary pattern is beneficial to health across populations and may translate a protective effect with certain cancers.
    Full-text · Article · Oct 2013 · BMC Surgery
Show more