Safranal Prevents Liver Cancer Through Inhibiting Oxidative Stress and Alleviating Inflammation.

Youssef Abdalla,Ali Abdalla,Amr Amin,Alaaeldin Ahmed Hamza

doi:10.3389/fphar.2021.777500

Abstract

Despite all efforts, an effective and safe treatment for liver cancer remains elusive. Natural products and their derived biomolecules are potential resources to mine for novel anti-cancer drugs. Chemopreventive effects of safranal, a major bioactive ingredient of the golden spice “saffron”, were evaluated in this study against diethylnitrosamine (DEN)–induced liver cancer in rats. Safranal’s mechanisms of action were also investigated in the human liver cancer line “HepG2”. When administered to DEN-treated rats, safranal significantly inhibited proliferation (Ki-67) and also induced apoptosis (TUNEL and M30 CytoDeath). It also exhibited anti-inflammatory properties where inflammatory markers such as NF-kB, COX2, iNOS, TNF-alpha, and its receptor were significantly inhibited. Safranal’s in vivo effects were further supported in HepG2 cells where apoptosis was induced and inflammation was downregulated. In summary, safranal is reported here as a potent chemopreventive agent against hepatocellular carcinoma that may soon be an important ingredient of a broad-spectrum cancer therapy.

Highlights

Cancer is one of the most common causes of illness and death worldwide
An increase in the number and area of placental glutathione S-transferase (GST-p) in the liver is a reliable marker of hepatocellular carcinoma (HCC) induced with carcinogens in the liver
GST-p was reduced in the livers of rats treated with safranal before cancer development compared with rats that were given only carcinogens

Summary

Introduction

Cancer is one of the most common causes of illness and death worldwide. In 2015, there were 17.5 million recorded cases of cancer and 9.5 million deaths from the disease, making it the second highest cause of death globally after heart disease (Zhou et al, 2016; Bray et al, 2018). Liver cancer is considered the fifth cause of death from cancer worldwide and the death rate from liver cancer represents 70% of deaths in African and Asian countries (Chessum et al, 2015; Plummer et al, 2016; Bray et al, 2018). There are a number of factors that lead to the spread of HCC in Asia and Africa, for instance, chronic hepatitis (B and C) infection, chronic alcohol consumption, exposure to environmental pollutants such as aflatoxin, and environmental carcinogens including nitrosamines (Plummer et al, 2016; Zhou et al, 2016). The initiation-promoting cancer development model, used in this study, mimics the early events of the latent period of human carcinogenesis

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Conclusion