The role of antioxidants in the era of cardio-oncology

Abstract

Although most chemotherapeutic drugs have the potential to exert cardiotoxicity, these drugs have been chosen for use in cancer treatment because survival and curability benefits outweigh the risk of these complications. Anthracyclines, for example, are a powerful class of chemotherapeutic agents; however, their use is restricted by dose-related cardiotoxicity. Experimental evidence strongly supports the role of reactive oxygen species in this process, suggesting that antioxidants may be effective in protecting the heart from toxicity. Clinical use of antioxidants to protect the heart during anthracycline chemotherapy has been controversial due to the potential for reduced cytotoxic efficacy toward cancer cells. Results from randomized clinical trials addressing whether antioxidants either reduce the incidence of clinical heart failure among patients undergoing anthracycline-based chemotherapy or reduce the response rates to anthracycline-based chemotherapy have been unclear. While anthracyclines are by far the most well-studied antitumor agents with cardiotoxic properties, evidence now shows that reactive oxygen species may play roles in cardiotoxicity induced by other chemotherapeutic agents such as cyclophosphamide, cisplatin, 5-fluorouracil, and trastuzumab. Thus, in the new era of combination therapy and long-term survival of cancer patients, the use of antioxidants to support cancer therapy should be revisited.

Signalling mechanisms underlying doxorubicin and Nox2 NADPH oxidase‐induced cardiomyopathy: involvement of mitofusin‐2

“…One of the major theories of the action of DOX is based on its interference with iron metabolism and generation of excess of ROS. However, although antioxidants, such as co‐enzyme Q10, N‐acetylcysteine and vitamins C and E, have been reported to exert cardioprotective effects in experimental models (Sterba et al, 2013), the results of small randomized clinical trials have not shown clear benefit (van Dalen et al, 2011; Vincent et al, 2013). The lack of success of antioxidant therapeutic strategies is likely to demonstrate the complexity of redox reactions in biological tissues (Madamanchi and Runge, 2013), in which ROS are known to serve both physiological and maladaptive roles.…”

Comparison of Metabolic Profiles of Normal and Cancer Cells in Response to Cytotoxic Agents

“…The use antioxidant combining to chemotherapy in cancer is a still controversial issue, but it has been recommended on the toxicity decrease of chemotherapy. 37,38 Since glutamine restores the level of glutathione reduced by chemotherapy, glutamine supplement was also used to reduce the chemotherapy-induced toxicity. 39,40 Branched amino acids, isoleucine, leucine, and valine showed the noticeable differences in response to cytotoxic agents between MRC5 and A549 cells.…”

Apoptosis-based therapy to treat pulmonary arterial hypertension

“…One reason we investigated this drug is that DNR was found to be an effective inducer of apoptosis in cultured human pulmonary artery smooth muscle cells (PASMCs) 6 . Another important reason was that since anthracyclines have cardiotoxic properties, particularly left ventricle (LV) toxicity, in cancer patients 5 , such drugs may serve as an excellent model for understanding how normal RVs and RVs affected by PAH may be influenced by anti-tumor drugs. While the RV and LV are generally thought to have identical molecular characteristics, our studies have revealed differential molecular-signaling mechanisms in the two ventricles 7,8 .…”

“…Notably, many anti-tumor drugs cause the death of cardiac myocytes, exerting cardiotoxicity 5 . Since PAH patients already suffer from RV dysfunctions, the use of such drugs, which could potentially worsen the cardiac problems in PAH patients, poses challenges.…”