Identification of (Z)-2,3-Diphenylacrylonitrile as Anti-Cancer Molecule in Persian Gulf Sea Cucumber Holothuria parva

Abstract

Hepatocellular carcinoma (HCC), also named cancerous hepatoma, is the most common type of malignant neoplasia of the liver. In this research, we screened the Persian Gulf sea cucumber Holothuria parva (H. parva) methanolic sub-fractions for the possible existence of selective toxicity on liver mitochondria isolated from an animal model of HCC. Next, we purified the most active fraction. Thus the structure of the active molecule was identified. HCC was induced by diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) protocol. Rat liver mitochondria for evaluation of the selective cytotoxic effects of sub-fractions of H. parva were isolated and then mitochondrial parameters were determined. Our results showed that C1 sub-fraction of methanolic extract of H. parva considerably increased reactive oxygen species (ROS) generation, collapse of mitochondrial membrane potential (MMP), swelling in mitochondria and cytochrome c release only on HCC liver mitochondria. Furthermore, the methanolic extract of H. parva was investigated furthermore and the active fraction was extracted. In this fraction, (Z)-2,3-diphenylacrylonitrile molecule, which is also known as α-cyanostilbene, was identified by mass analysis. This molecule increased ROS generation, collapse of MMP, swelling in mitochondria and finally cytochrome c release only on HCC liver mitochondria. The derivatives of (Z)-2,3-diphenylacrylonitrile in other natural products were also reported as an anti-cancer agent. These results suggest the eligibility of the (Z)-2,3-diphenylacrylonitrile as a complementary therapeutic agent for patients with HCC.

Sea Cucumber (Stichopus japonicas) F2 Enhanced TRAIL-Induced Apoptosis via XIAP Ubiquitination and ER Stress in Colorectal Cancer Cells

“…Many studies have reported that sea cucumber extract contains several compounds, including mono sulfated tritepenoid glycoside Frondoside A, disulfated glycoside Frondoside B, trisulfated glycoside Frondoside C, eicosapentaenoic acid, fucosylated chondroitin sulfate, nobiliside D, 12-methyltetradecanoic acid, sphingoid and canthaxanthin/astaxanthin, that have induced apoptosis in solid cancers, including breast, liver, renal, cervical, lung, and colorectal cancer cells [15,24,25,26]. Amidi et al reported that (Z)-2,3-diphenylacrylonitrile molecules isolated from Persian Gulf SC were identified as potential anti-cancer agents [27]. In our study, the crude and fractionated sulfated fucan from the sea cucumber, Stichopus japonicas , was used to investigate its anti-tumor activity [17].…”

Marine natural products

“…exhibited cytotoxicity and were strong kinase inhibitors, 710 and (Z)-2,3diphenylacrylonitrile (Holothuria parva) caused an increase in ROS generation and collapse of the mitochondrial membrane potential in hepatocellular carcinoma cells. 711 Puried spinochromes, naphthoquinones from urchins, exhibit wide ranging activities against bacteria, as antioxidants, as pro-inammatory agents and as cytotoxins. 712 Mature eggs of the sand dollar Scaphechinus mirabilis contain a jelly coat bearing pigment cells which contain spinochromes D and E, and to a lesser degree, spinochrome A and echinochrome A.…”

Acute glucose fluctuation promotes RAGE expression via reactive oxygen species‑mediated NF‑κB activation in rat podocytes

“…However, the apoptosis rate measured by flow cytometry was not statistically significant, which is similar to the results of a study using human umbilical vein endothelial cells, which found that AGF failed to induce cell apoptosis ( 26 ). Extensive studies have indicated that apoptosis and proliferation are mediated by increased levels of ROS ( 27 ). ROS plays a dual role in tissue injury, as moderate levels of ROS promote cell survival and proliferation, whereas excessive ROS production can directly induce necrocytosis ( 28 ).…”