Role of nitric oxide and metallothionein in cytotoxic activity of cadmium in CACO-2 cells

Farnaz Malekmarzban, Mohammad Seyedabadi, Mohammad Hossein Ghahremani, Shima Aliebrahimi, Peiman Habibollahi, Shohreh Tavajohi, Seyed Nasser Ostad

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Cadmium (Cd) induces carcinogenicity and cytotoxicity through a variety of mechanisms. Metallothioneins (MTs) play critical roles in metal detoxification and radical scavenging. Here we evaluated the possible involvement of NO and MT in Cd-induced toxicity and resistance development. By utilizing Cd-resistant Caco-2 cells as a model of chronic exposure to Cadmium, we observed that Cd decreased Caco-2 cell proliferation, whereas Cd-resistant cells showed a lower sensitivity to Cd cytotoxicity. L-NAME as an iNOS inhibitor and cPTIO as an NO scavenger induced a significant reduction in Cd-mediated toxicity of parent Caco-2 in spite of resistant cells. In resistant cells, iNOS mRNA expression was declined; however, MT protein synthesis was increased following acute and chronic Cd exposure. It seems that NO synthesis involves in Cd-induced cytotoxicity, while elevated MT expression is associated with Cd detoxification and resistance.

Original languageEnglish (US)
Pages (from-to)287-294
Number of pages8
JournalActa Medica Iranica
Issue number5
StatePublished - 2018


  • Colon carcinoma
  • Detoxification
  • Free radical
  • Heavy metal
  • iNOS

ASJC Scopus subject areas

  • Medicine(all)


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