Selective Toxicity of Non Polar Bioactive Compounds of Persian Gulf Sea Squirt Phallusia Nigra on Skin Mitochondria Isolated from Rat Model of Melanoma

Abstract

<br /> <strong><span style="font-size: small;">Background: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Skin cancer is the most prevalent cancer and one of the major causes of mortality worldwide. Marin animals have attracted much attention in recent years as useful substances having application in medicine. It was shown that Phallusia nigra (P. nigra) known as sea squirt could play an important role in cancer therapy. </span></span><strong><span style="font-size: small;">Methods: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">This study </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">was designed to figure out the probable selective toxicity of n-hexane, diethyl ether, methanolic and aqueous extracts </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">of P. nigra on cancerous mitochondria isolated from the skin of melanoma induced rats. In our study, mitochondria were isolated from the skin tissue of both melanoma induced and normal healthyrats. Different concentrations of four </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">different extracts of P. nigra (250, 500 and 1000 μg/ml) were added to mitochondrial samples obtained from both groups, </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">separately. </span></span><strong><span style="font-size: small;">Results: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Our results showed that n-hexane, diethyl ether and methanolic extracts (but not aqueous extract) of P. nigra in all concentrations applied (250, 500 and 1000 μg/ml) significantly induced toxic alterations only in the cancerous but not normal healthy skin mitochondria including; increased reactive oxygen species (ROS) formation, </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">mitochondrial swelling, decreased mitochondrial membrane potential (MMP) and cytochrome c release. Flow-cytometry </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">analysis demonstrated that n-hexane, diethyl ether and methanolic extracts of P. nigra progressively induced apoptosis </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">and necrosis only on melanoma cells but not healthy skin cells. </span></span><strong><span style="font-size: small;">Conclusions: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Our results suggest that non polar bioactive </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">compounds in P. nigra may be hopeful candidates for further studies including molecular identification, confirmatory in vivo experiments and finally clinical trials designed for new drug treatment of melanoma skin cancer. </span></span>