TY - JOUR
T1 - Targeting the mitochondrial VDAC in hepatocellular carcinoma using a polyclonal antibody-conjugated to a nitrosyl ruthenium complex
AU - Ramos, Loyanne C.B.
AU - Rodrigues, Fernando P.
AU - Biazzotto, Juliana C.
AU - de Paula Machado, Sergio
AU - Slep, Leonardo D.
AU - Hamblin, Michael R.
AU - da Silva, Roberto S.
N1 - Publisher Copyright:
© 2018, SBIC.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - The rational design of anti-cancer agents includes a new approach based on ruthenium complexes that can act as nitric oxide (NO) donor agents against specific cellular targets. One of the most studied classes of those compounds is based on bis(bipyridine) ruthenium fragment and its derivative species. In this work, we present the chemical and cytotoxicity properties against the liver hepatocellular carcinoma cell line HepG2 of cis-[RuII(NO+)Cl(dcbpy)2]2− conjugated to a polyclonal antibody IgG (anti-VDAC) recognizing a cell surface marker. UV–visible bands of the ruthenium complex were assigned with the aid of density functional theory, which also allowed estimation of the structures that explain the biological effects of the ruthenium complex–IgG conjugate. The interaction of cis-[RuII(NO+)Cl(dcbpy)2]3− with mitochondria was evaluated due to the potential of these organelles as anti-cancer targets, and considering they interact with the anti-VDAC antibody. The cytotoxicity of cis-[RuII(NO+)Cl(dcbpy)2]3−-anti-VDAC antibody was up to 80% greater in comparison to the free cis-[RuII(NO+)Cl(dcbpy)2]3− complex. We suggest that this effect is due to site-specific interaction of the complex followed by NO release.
AB - The rational design of anti-cancer agents includes a new approach based on ruthenium complexes that can act as nitric oxide (NO) donor agents against specific cellular targets. One of the most studied classes of those compounds is based on bis(bipyridine) ruthenium fragment and its derivative species. In this work, we present the chemical and cytotoxicity properties against the liver hepatocellular carcinoma cell line HepG2 of cis-[RuII(NO+)Cl(dcbpy)2]2− conjugated to a polyclonal antibody IgG (anti-VDAC) recognizing a cell surface marker. UV–visible bands of the ruthenium complex were assigned with the aid of density functional theory, which also allowed estimation of the structures that explain the biological effects of the ruthenium complex–IgG conjugate. The interaction of cis-[RuII(NO+)Cl(dcbpy)2]3− with mitochondria was evaluated due to the potential of these organelles as anti-cancer targets, and considering they interact with the anti-VDAC antibody. The cytotoxicity of cis-[RuII(NO+)Cl(dcbpy)2]3−-anti-VDAC antibody was up to 80% greater in comparison to the free cis-[RuII(NO+)Cl(dcbpy)2]3− complex. We suggest that this effect is due to site-specific interaction of the complex followed by NO release.
KW - Conjugated ruthenium-antibody complex
KW - Nitric oxide delivery agent
KW - Nitrosyl ruthenium complexes
UR - http://www.scopus.com/inward/record.url?scp=85049590800&partnerID=8YFLogxK
U2 - 10.1007/s00775-018-1589-x
DO - 10.1007/s00775-018-1589-x
M3 - Article
C2 - 29971501
AN - SCOPUS:85049590800
SN - 0949-8257
VL - 23
SP - 903
EP - 916
JO - Journal of Biological Inorganic Chemistry
JF - Journal of Biological Inorganic Chemistry
IS - 6
ER -