title: Enhanced anticancer effect of Combretastatin A-4 phosphate when combined with vincristine in the treatment of hepatocellular carcinoma.
abstract: Tubulin targeting agents have received considerable interest as a potential tumor-selective vascular disrupting agents, which represent another avenue for cancer growing therapeutic opportunities. Hence, the present study was conducted to investigate the anti-tumor activity of Combretastatin A-4 phosphate (CA4-P) and vincristine against hepatocellular carcinoma in rats, by individual administration and in combination. In vitro study was conducted using human hepatocellular carcinoma cell lines, showed that CA4-P and vincristine have a potent cell cytotoxic and tubulin inhibitory effect. In addition, a remarkable synergistic effect was observed by the simultaneous application of both drugs. Whereas in vivo study was conducted using model of rat liver cancer initiated with DENA and promoted by CCl4, showed that CA4-P and vincristine were significantly decreased liver relative weight, number of hepatic nodules and there relative volumes, tubulin content of the hepatic tissue, GSH and AFP. On the other hand, co-administration of both drugs exhibited significant further decrements in these parameters. Whereas a marked increase in MDA, carbonyl content and TNF-α inside hepatic tissue were observed in the treated groups and these increments were more prominent by co-administration of both drugs. In conclusion CA4-P showed a potential anti-cancer activity against hepatocellular carcinoma and this effect was greatly enhanced by co-administration with vincristine. Additionally, our new findings provided an important evidence that the anticancer activity of drugs with a narrow therapeutic window such as vincristine can be greatly improved by its co-administration with CA4-P providing more enhanced activity with less side effects.
authors.affiliation: Department of Pharmacology and Toxicology, South Valley University, 6 Km, Qena Safaga Road, Qena, Egypt. Electronic address: esam_pharma@yahoo.com.
authors.forename: Esam M
authors.initials: EM
authors.lastname: Aboubakr
authors.affiliation: Department of Pharmacology and Toxicology, Minia University, Ard Shalaby, Misr-Aswan Road, El-Minia, Egypt. Electronic address: ashraf_taye70@yahoo.com.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Taye
authors.affiliation: Department of Medicinal Chemistry, Minia University, Ard Shalaby, Misr-Aswan Road, El-Minia, Egypt. Electronic address: omarsokkar@yahoo.com.
authors.forename: Omar M
authors.initials: OM
authors.lastname: Aly
authors.affiliation: Cancer Biology, Center of excellence for advanced sciences, National Research Center, El Buhouth St., Dokki, Cairo, Egypt. Electronic address: aeldeen7@yahoo.com.
authors.forename: Amira M
authors.initials: AM
authors.lastname: Gamal-Eldeen
authors.affiliation: Department of Pharmacology and Toxicology, Minia University, Ard Shalaby, Misr-Aswan Road, El-Minia, Egypt. Electronic address: m_moselhy64@yahoo.com.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: El-Moselhy
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002251:Carbon Tetrachloride; D045744:Cell Line, Tumor; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D009929:Organ Size; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013267:Stilbenes / Q000008:administration & dosage; D014404:Tubulin / Q000378:metabolism; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D013267:Stilbenes; D014404:Tubulin; D014750:Vincristine; D002251:Carbon Tetrachloride; C058728:fosbretabulin
keywords: Combretastatin; Hepatic cancer; Tubulin; Vascular disrupting agents; Vincristine