• Effects of Pomegranate fruit and Pomegranate molasses on induced oxidative stress by chromium in colorectal cancer
  • Samna Mohammadzadeh,1,* Mohammad Hassan Emami,2 Safoora Mohammadzadeh,3 Fatemeh Maghool,4 Aida Heidari2,5
    1. Poursina Hakim Digestive Diseases Research Center, Isfahan University of medical sciences, Isfahan, Iran
    2. Poursina Hakim Digestive Diseases Research Center, Isfahan University of medical sciences, Isfahan, Iran
    3. Poursina Hakim Digestive Diseases Research Center, Isfahan University of medical sciences, Isfahan, Iran
    4. Poursina Hakim Digestive Diseases Research Center, Isfahan University of medical sciences, Isfahan, Iran
    5. Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Sciences and Technologies, University of Isfahan, Isfahan, Iran


  • Introduction: High levels of heavy metals such as chromium (Cr) in the environment are related with the colorectal cancer incidence. Cr induces toxicity and carcinogenesis via oxidative stress and oxidative tissue injuries. Cr-induced oxidative stress may promote colorectal cancer. Pomegranate and pomegranate molasses are the good sources of antioxidants, may be modulated Cr-induced damages. This review aims to highlight the protective properties of
  • Methods: For this review, the electronic database was searched using the search words colorectal cancer, Chromium, carcinogenesis, oxidative stress and pomegranate and pomegranate molasses. Only English published articles between 2000 until 2021 have been included.
  • Results: Chromium leads to oxidative stress by production of free radicals such as superoxide, singlet oxygen, nitric oxide, hydrogen peroxide, and the peroxylradical. This heavy metal could induce physiological and biochemical impairments by interacting with enzymes (eg., antioxidant enzymes), lipids, proteins, and genetic material (DNA and/or RNA). In addition, Cr- induced oxidative stress products could cause damages of membrane, degradation and deactivation of genetic material, and proteins (enzymes) directly or indirectly which led to antioxidant/oxidant imbalances, growth inhibition and programmed cell death activation. Pomegranate fruits (Punica granatum L.) and their molasses are natural agents which used in many in vitro and in vivo studies. Several studies reported that pomegranate had the highest anti-oxidative, anti-proliferative and pro-apoptotic effects on colorectal cell lines (HT-29, HCT116, SW480, SW620) and could reduce colon cancer risk. Pomegranate showed reduction of inflammation in HT-29 cancer cells by down-regulation of inflammatory signaling pathways, such as inhibition of tumor necrosis factor-α, and cyclooxygenase2; and suppression of nuclear factor kappa B and Protein kinase B activities. In Caco-2 and HT29 colon cancer cells, pomegranate released mitochondrial cytochrome c into the cytosol, activated caspase-3 and -9, and down-regulated anti-apoptotic Bcl-xL, decreased cyclins expression, arrested cells in S phase of cell-cycle that resulted in induction of apoptosis and inhibition of proliferation. In vivo studies on mouse models showed that pomegranate could protect proteins and DNA against oxidation. Pomegranate and their molasses are a source of polyphenolic (such as anthocyanins and phenolic acids, anthocyanins, ellagitannins, and hydrolysable tannins), flavonoids, polysaccharides, vitamins, and minerals which could represent protective activity against oxidative stress by scavenging free radicals, and inhibiting oxidation of macromolecules. Moreover, some previous in vivo studies showed that pomegranate molasses had strong antioxidant properties, four times more than Pomegranate juice that could decrease lipid peroxidation, and increase superoxide dismutase activity. Antioxidant properties of pomegranate molasses is related to high levels of phenolic acid, flavonoid, vitamin C, gallic acid, rutin & ellagic acid. In an animal study, pomegranate molasses reduced both the toxicity and oxidative stress of toxic material. Anticancer, anti-oxidative and anti-inflammatory properties of pomegranate in particular pomegranate molasses probably could be reduced Cr-induced oxidative stress and inflammation in cancer sites and might accelerate the elimination of colorectal tumor.
  • Conclusion: Pomegranate and pomegranate molasses with powerful antioxidant, anti-inflammatory, anti-proliferative, and anti-tumorigenic properties assumed as promising chemopreventive agent which probably could decrease Cr- induced toxicity and could be used in combination with conventional treatments for cancer prevention.
  • Keywords: colorectal cancer, Chromium, carcinogenesis, oxidative stress, pomegranate, pomegranate molasses