Plant Polyphenols as Chemopreventive Agents for Lung Cancer.

Madumani Amararathna,H P Vasantha Rupasinghe,Michael R Johnston

doi:10.3390/ijms17081352

Madumani Amararathna, H P Vasantha Rupasinghe + Show 1 more

Open Access

https://doi.org/10.3390/ijms17081352

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Abstract

Lung cancer may be prevented by a diet rich in fruits and vegetables as they are enriched with dietary antioxidant polyphenols, such as flavonoids, proanthocyanidins, lignans, stilbenes, and phenolic acids. Dietary polyphenols exert a wide range of beneficial biological functions beyond their antioxidative properties and are involved in regulation of cell survival pathways leading to anticarcinogenic and antimutagenic functions. There are sufficient evidence from in vitro, in vivo, and epidemiological studies to suggest that the dietary intervention of polyphenols in cancer prevention, including the chemopreventive ability of dietary polyphenols, act against lung carcinogens. Cohort and epidemiological studies in selected risk populations have evaluated clinical effects of polyphenols. Polyphenols have demonstrated three major actions: antioxidative activity, regulation of phase I and II enzymes, and regulation of cell survival pathways against lung carcinogenesis. They have also shown an inverse association of lung cancer occurrences among high risk populations who consumed considerable amounts of fruits and vegetables in their daily diet. In in vitro cell culture experimental models, polyphenols bind with electrophilic metabolites from carcinogens, inactivate cellular oxygen radicals, prevent membrane lipid peroxidation and DNA oxidative damage, and adduct formation. Further, polyphenols enhance the detoxifying enzymes such as the phase II enzymes, glutathione transferases and glucuronosyl transferases.

Highlights

Worldwide cancer statistics document the devastating effects of lung cancer
Plant polyphenols have exhibited multiple modes of cancer prevention functions: (i) polyphenols act as antioxidants and regulate oxidative stress caused by the lung carcinogens; they mediate oxidative DNA damage, lipid autoxidation, and cell membrane damage; (ii) polyphenols inhibit the activation of cytochrome 450 enzymes, which form reactive electrophilic metabolites from pro-carcinogens
These reactive intermediary metabolites can covalently bind with DNA specific sites and form DNA adducts which activate oncogenes and suppress tumor suppressor genes, leading to lung cancer; and (iii) polyphenols enhance the activity of phase II detoxification enzymes, which are able to detoxify electrophilic metabolites from phase I enzymes and excrete them through urine and bile

Summary

Introduction

Worldwide cancer statistics document the devastating effects of lung cancer. Among all types of cancer, lung cancer has caused almost one fifth of cancer deaths (19.4%). As per the World Health Organization (WHO), at least one-third of all cancer cases are preventable through dietary modifications and lifestyle changes Eliminating risk factors, such as cigarette smoke and polluted environments, and adopting safety measures at work are a few actions for lung cancer prevention suggested by the WHO [3,4,5]. A population-based case control study (1061 cases and 1425 controls) conducted by Christensen and colleagues (2012) has shown that lower dietary flavonoid intake can increase the lung cancer risk. They found an inverse association between intake of flavone and flavanone-rich diets and squamous cell carcinoma incidences, but no association was found with adenocarcinoma incidences [34]. Non-small cell lung cancer (NSCLC) cell—A549, H460, H1299; human adenocarcinoma cell—PC-9; small cell lung cancer (SCLC) cell—NCI-H209; extracellular signal-regulated kinase—ERK; adenosine diphosphate—ADP; cyclin dependent kinase—CDK; and matrix metalloproteinase—MMP

Environmental and Occupation Lung Carcinogens

Group 4

In Vivo Studies

Epidemiological Evidence of Lung Cancer Prevention

Findings

Conclusions