Regression of Dalton's lymphoma in vivo via decline in lactate dehydrogenase and induction of apoptosis by a ruthenium(II)-complex containing 4-carboxy N-ethylbenzamide as ligand.
A novel ruthenium(II)-complex containing 4-carboxy N-ethylbenzamide (Ru(II)-CNEB) was found to interact with and inhibit M4-lactate dehydrogenase (M4-LDH), a tumor growth supportive enzyme, at the tissue level. The present article describes modulation of M4-LDH by this compound in a T-cell lymphoma (Dalton's Lymphoma: DL) vis a vis regression of the tumor in vivo. The compound showed a dose dependent cytotoxicity to DL cells in vitro. When a non toxic dose (10 mg/kg bw i.p.) of Ru(II)-CNEB was administered to DL bearing mice, it also produced a significant decline in DL cell viability in vivo. The DL cells from Ru(II)-CNEB treated DL mice showed a significant decline in the level of M4-LDH with a concomitant release of this protein in the cell free ascitic fluid. A significant increase of nuclear DNA fragmentation in DL cells from Ru(II)-CNEB treated DL mice also coincided with the release of mitochondrial cytochrome c in those DL cells. Importantly, neither blood based biochemical markers of liver damage nor the normal patterns of LDH isozymes in other tissues were affected due to the treatment of DL mice with the compound. These results were also comparable with the effects of cisplatin (an anticancer drug) observed simultaneously on DL mice. The findings suggest that Ru(II)-CNEB is able to regress Dalton's lymphoma in vivo via declining M4-LDH and inducing mitochondrial dysfunction-apoptosis pathway without producing any toxicity to the normal tissues.
Koiri
Raj K
RK
Biochemistry & Molecular Biology Laboratory, Centre of Advanced Studies in Zoology, Banaras Hindu University, Varanasi, 221005, India.
Trigun
Surendra K
SK
Mishra
Lallan
L
Pandey
Kiran
K
Dixit
Deobrat
D
Dubey
Santosh K
SK
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001202:Ascitic Fluid / Q000187:drug effects / Q000473:pathology; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001549:Benzamides / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D056831:Coordination Complexes / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D053938:DNA Fragmentation / Q000187:drug effects; D007527:Isoenzymes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D008024:Ligands; D008223:Lymphoma / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D012074:Remission Induction; D012428:Ruthenium / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D016019:Survival Analysis
D001549:Benzamides; D056831:Coordination Complexes; D007527:Isoenzymes; D008024:Ligands; C579797:bis(2,2'-bipyridine)(4-carboy N-ethylbenzamide)ruthenium(II); C098348:N-ethylbenzamide; D012428:Ruthenium; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002945:Cisplatin