Therapeutic potential of ghrelin and des-acyl ghrelin against chemotherapy-induced cardiotoxicity

Abstract

Abstract.Cancer was considered an incurable disease for many years; however, with the development of anticancer drugs and state-of-the art technologies, it has become curable. Cardiovascular diseases in patients with cancer or induced by cancer chemotherapy have recently become a great concern. Certain anticancer drugs and molecular targeted therapies cause cardiotoxicity, which limit the widespread implementation of cancer treatment and decrease the quality of life in cancer patients significantly. The anthracycline doxorubicin (DOX) causes cardiotoxicity. The cellular mechanism underlying DOX-induced cardiotoxicity include free-radical damage to cardiac myocytes, leading to mitochondrial injury and subsequent death of myocytes. Recently, circulating orexigenic hormones, ghrelin and des-acyl ghrelin, have been reported to inhibit DOX-induced cardiotoxicity. However, little is known about the molecular mechanisms underlying their preventive effects. In the present study, we show the possible mechanisms underlying the effects of ghrelin and desacyl ghrelin against DOX-induced cardiotoxicity through in vitro and in vivo researches.

Three-dimensional growth of breast cancer cells potentiates the anti-tumor effects of unacylated ghrelin and AZP-531

“…As less than 1% of breast tumors carry these mutations ( Tilch et al, 2014 ), it is likely that unacylated ghrelin and AZP-531 will be effective in the majority of breast cancers. Since unacylated ghrelin has also been shown to prevent chemotherapy-induced muscle cell death ( Nonaka et al, 2017 ), there is potential to combine unacylated ghrelin or AZP-531 with chemotherapy, while also reducing cardiotoxicity.…”

Unacylated ghrelin and AZP531 suppress the 3D growth of breast cancers

“…As less than 1% of breast tumors carry these mutations (Tilch et al, 2014), it is likely that unacylated ghrelin and AZP531 will be effective in the majority of breast cancers. Since UAG has also been shown to prevent chemotherapyinduced muscle cell death (Nonaka et al, 2017), there is potential to combine unacylated ghrelin or AZP531 with chemotherapy, while also reducing cardiotoxicity.…”

Effect of Ghrelin on the Cardiovascular System

“…Des-acyl ghrelin was reported to suppress the apoptosis of myocardial and vascular endothelial cells. Recently, it was shown that des-acyl ghrelin improved cardiac function in the settings of cardiotoxicity induced by the anticancer drug doxorubicin and myocardial impairment associated with cachexia [ 56 ]. It is believed that the receptor mediating des-acyl ghrelin-dependent effects are distinct from GHS-R.…”