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Mar Drugs
2017 Oct 16;1510:. doi: 10.3390/md15100314.
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Identification of (Z)-2,3-Diphenylacrylonitrileas Anti-Cancer Molecule in Persian Gulf Sea Cucumber Holothuria parva.
Amidi S
,
Hashemi Z
,
Motallebi A
,
Nazemi M
,
Farrokhpayam H
,
Seydi E
,
Pourahmad J
.
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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.
Figure 1. Thin layer chromatography (TLC) of fractionation methanolic extract using MeOH:CHCl3 (7:3) as mobile phase. The first ultraviolet (UV)-distinct band from top was named A, the second B, and the third C.
Figure 2. The fractionation of the active fraction (C) using MeOH:CHCl3 (7:3) as mobile phase by TLC plate method. C1 was the first UV-distinct band, and C2 was the second UV-distinct band.
Figure 4. The Mitochondrial Membrane Potential (MMP) assay. The effect of C1 sub-fraction of methanolic extract of H. parva (250, 500 and 1000 μg/mL) on MMP collapse in: the normal mitochondria (A); and the HCC mitochondria (B) obtained from liver hepatocytes at within 60 min of incubation. The cytochrome c release assay. (A) Control means vehicle treated normal mitochondria. (B) Control means vehicle treated HCC mitochondria. *** and **** indicate significant differences in comparison with corresponding control (HCC) groups for p < 0.001 and p < 0.0001, respectively. (C) The effect of C1 sub-fraction of methanolic extract of H. parva (500 μg/mL) on cytochrome c release in the normal mitochondria and the HCC mitochondria obtained from liver hepatocytes at within 60 min of incubation. Data are shown as mean ± SD (n = 3). *** indicate significant differences in comparison with corresponding control (HCC) groups for p < 0.001. ### Significant differences in the comparison with 500 μM (HCC) C1 sub-fraction (p < 0.001).
Figure 5. The mass (MS) Analysis of the C1 Sub-fraction.
Figure 7. The Mitochondrial Membrane Potential (MMP) assay. The effect of (Z)-2,3-diphenylacrylonitrile of H. parva (10, 20 and 40 μg/mL) on MMP collapse in: the normal mitochondria (A); and the HCC mitochondria (B) obtained from liver hepatocytes at within 60 min of incubation. (A) Control means vehicle treated normal mitochondria; (B) Control means vehicle treated HCC mitochondria; (C) The cytochrome c release assay. The effect of (Z)-2,3-diphenylacrylonitrile of H. parva (20 μg/mL) on cytochrome c release in the normal mitochondria and the HCC mitochondria obtained from liver hepatocytes at within 60 min of incubation; (D) MTT assay: Hepatocytes obtained from HCC group were treated with (Z)-2,3-diphenylacrylonitrile of H. parva (0, 2.5, 5, 10, 20, 40 and 100 μg/mL) and incubated for 24 h. Data are shown as mean ± SD (n = 3). *, **, *** and **** indicate significant differences in comparison with corresponding control (HCC) groups for p < 0.001 and p < 0.0001, respectively. ### Significant differences in the comparison with 20 μg/mL (HCC) (Z)-2,3-diphenylacrylonitrile (p < 0.001).
Figure 8. A mix probe between synthesized (Z)-2,3-diphenylacrylonitrile and C1 fraction in TLC. C: Possible main active ingredient of C1 fraction. S, Synthesized (Z)-2,3-diphenylacrylonitrile; *, both the possible main active ingredient of C1 fraction and synthesized (Z)-2,3-diphenylacrylonitrile.
Alam,
Synthesis and evaluation of (Z)-2,3-diphenylacrylonitrile analogs as anti-cancer and anti-microbial agents.
2013, Pubmed
Alam,
Synthesis and evaluation of (Z)-2,3-diphenylacrylonitrile analogs as anti-cancer and anti-microbial agents.
2013,
Pubmed
Bradford,
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
1976,
Pubmed
Cai,
A Halogen-Containing Stilbene Derivative from the Leaves of Cajanus cajan that Induces Osteogenic Differentiation of Human Mesenchymal Stem Cells.
2015,
Pubmed
Chinembiri,
Review of natural compounds for potential skin cancer treatment.
2014,
Pubmed
de Medina,
Synthesis and biological properties of new stilbene derivatives of resveratrol as new selective aryl hydrocarbon modulators.
2005,
Pubmed
Forner,
Hepatocellular carcinoma.
2012,
Pubmed
Hosseini,
Toxicity of copper on isolated liver mitochondria: impairment at complexes I, II, and IV leads to increased ROS production.
2014,
Pubmed
Janakiram,
Sea Cucumbers Metabolites as Potent Anti-Cancer Agents.
2015,
Pubmed
,
Echinobase
Kim,
Design, synthesis, and discovery of novel trans-stilbene analogues as potent and selective human cytochrome P450 1B1 inhibitors.
2002,
Pubmed
Liang,
Synthesis, in vitro and in vivo antitumor activity of symmetrical bis-Schiff base derivatives of isatin.
2014,
Pubmed
Mayer,
Marine pharmacology in 2007-8: Marine compounds with antibacterial, anticoagulant, antifungal, anti-inflammatory, antimalarial, antiprotozoal, antituberculosis, and antiviral activities; affecting the immune and nervous system, and other miscellaneous mechanisms of action.
2011,
Pubmed
Pourahmad,
A comparison of hepatocyte cytotoxic mechanisms for thallium (I) and thallium (III).
2010,
Pubmed
Pourahmad,
A search for hepatoprotective activity of fruit extract of Mangifera indica L. against oxidative stress cytotoxicity.
2010,
Pubmed
Rasool,
New possibilities in hepatocellular carcinoma treatment.
2014,
Pubmed
Roberti,
Synthesis and biological evaluation of resveratrol and analogues as apoptosis-inducing agents.
2003,
Pubmed
Sadighara,
Toxicity of Atorvastatin on Pancreas Mitochondria: A Justification for Increased Risk of Diabetes Mellitus.
2017,
Pubmed
Salimi,
Selective toxicity of persian gulf sea cucumber holothuria parva on human chronic lymphocytic leukemia b lymphocytes by direct mitochondrial targeting.
2017,
Pubmed
,
Echinobase
Sawadogo,
A survey of marine natural compounds and their derivatives with anti-cancer activity reported in 2011.
2013,
Pubmed
Seydi,
Selective Toxicity of Persian Gulf Sea Cucumber (Holothuria parva) and Sponge (Haliclona oculata) Methanolic Extracts on Liver Mitochondria Isolated from an Animal Model of Hepatocellular Carcinoma.
2015,
Pubmed
,
Echinobase
Seydi,
Myricetin Selectively Induces Apoptosis on Cancerous Hepatocytes by Directly Targeting Their Mitochondria.
2016,
Pubmed
Seydi,
Selective Toxicity of Apigenin on Cancerous Hepatocytes by Directly Targeting their Mitochondria.
2016,
Pubmed
Taha,
Potential chemoprevention of diethylnitrosamine-initiated and 2-acetylaminofluorene-promoted hepatocarcinogenesis by zerumbone from the rhizomes of the subtropical ginger (Zingiber zerumbet).
2010,
Pubmed
