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Troxerutin with copper generates oxidative stress in cancer cells: Its possible chemotherapeutic mechanism against hepatocellular carcinoma.
- Source :
-
Journal of cellular physiology [J Cell Physiol] 2018 Mar; Vol. 233 (3), pp. 1775-1790. Date of Electronic Publication: 2017 Aug 03. - Publication Year :
- 2018
-
Abstract
- Troxerutin (TXER) a rutin derivative is known for its anticancer effect against hepatocellular carcinoma (HCC). As part of large study, recently we have shown TXER interact with genetic material and its anti-mutagenic property. In the present study we have explored its possible mode of action in HCC. Since TXER alone did not show significant anticancer effect on Huh-7 cells, in vitro biochemical assays were performed for determining anticancer efficacy of TXER + metal complex using transition metals such as Cu, Zn, and Fe. The anticancer efficacy of TXER + Cu on Huh-7 cells were evaluated using MTT assay, DCFDA, JC-1 staining, comet assay, cell cycle analysis, immunocytochemistry, and Western blotting. Non-toxic nature of TXER was analyzed on primary rat hepatocytes. The in vivo efficacy of TXER was tested in N-nitrosodiethylamine initiated and γ-benzene hexachloride and partial hepatectomy promoted rat liver cancer. Liver markers, transition metal levels, histopathological examination, and expression levels of GST-P, 8-OHdG and Ki-67 were studied to assess the in vivo anticancer effect of TXER. We observed that TXER + Cu induced extensive cellular death on Huh-7 cells through generating free radicals and did not possess any toxic effect on normal hepatocytes. The in vivo studies revealed that TXER possess significant anti-cancer effect as assessed through improved liver markers and suppressed GST-P, 8-OHdG, and Ki-67 expression. TXER treatment reduced the hepatic Cu level in cancer bearing animals. Current study brings the putative mechanism involved in anti-cancer effect of TXER, further it will help to formulate phytoconstituents coupled anti-cancer drug for effective treatment of HCC.<br /> (© 2017 Wiley Periodicals, Inc.)
- Subjects :
- 8-Hydroxy-2'-Deoxyguanosine
Animals
Apoptosis drug effects
Catalase metabolism
Cell Line, Tumor
DNA Damage drug effects
Deoxyguanosine analogs & derivatives
Deoxyguanosine biosynthesis
Glutathione S-Transferase pi biosynthesis
Humans
Hydroxyethylrutoside pharmacology
Ki-67 Antigen biosynthesis
Liver metabolism
Rats
Rats, Wistar
Superoxide Dismutase metabolism
Superoxides metabolism
Antineoplastic Agents pharmacology
Carcinoma, Hepatocellular drug therapy
Coordination Complexes pharmacology
Copper pharmacology
Hydroxyethylrutoside analogs & derivatives
Liver Neoplasms drug therapy
Oxidative Stress drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4652
- Volume :
- 233
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of cellular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 28628229
- Full Text :
- https://doi.org/10.1002/jcp.26061