Polyphenolic-enriched olive leaf extract attenuated doxorubicin-induced cardiotoxicity in rats via suppression of oxidative stress and inflammation

Background The therapeutic value of doxorubicin as an effective anti-neoplastic agent is limited by its cardiotoxic side effects. We investigated the effects of ethanolic leaf extracts of olive leaf OL on cardiotoxicity as well as oxidative stress which was induced by doxorubicin (DOX) in Wistar rats. The cardiotoxicity was induced by intraperitoneally injecting a single dose of doxorubicin (10 mg kg−1) after 7 days of OL administration. OL was given by gastric gavage in 250 mg/kg, 500 mg/kg and 1000 mg/kg doses of extract for 10 days. Results Cardiac toxicity of DOX was evidenced by histopathological changes in cardiac tissues and an increase in the activities of serum markers of heart damage (AST and CK). DOX caused oxidative stress as evidenced by the elevation of malondialdehyde, protein carbonyl content levels, and catalase activity. That stress was also accompanied by a concurrent depletion of the activity of superoxide dismutase within cardiac tissues. The cardiotoxicity and oxidative stress damages caused by DOX also coincided with an increase of myeloperoxidase activity and iNOS expression. Most of these doxorubicin-induced biochemical and histological alterations were effectively attenuated by prior administration of OL. OL combination with DOX significantly increased its cytotoxicity in HepG2 liver cancer cell line and IC50 dropped from 259.35 to 158.12 μg/ml. Conclusion OL potentiated the cytotoxicity of DOX in liver cancer cell line and may play a role in the protection against its cardiotoxicity and thus can be a useful adjuvant therapy where doxorubicin is the common liver cancer-treating drug.

An Approach to Treatment of Liver Cancer by Novel Glycyrrhizin Derivative

Background: Liver cancer is a life threating disease as it is the fifth most common cancer and the third most common cause of death worldwide with no safe, efficient, and economic drug available for treatment. Methods: This study intended to investigate glycyrrhizin and its derivatives for possible use as a cytotoxic agent and as a drug for liver cancer treatment. Thus, after treatment of liver cancer cell line HepG-2 with 50 μM of each compound, cell viability was determined. Results: The cytotoxicity assay showed glycyrrhizin derivatives ME-GA (18β-Glycyrrhetinic-30-methyl ester) and AKBA (3-acetyl-11- keto-β-Boswellic acid) to be the most potent drug against liver cancer cell line HepG-2 with IC50 values 25.50 ± 1.06 and 19.73 ± 0.89 μM, respectively. Both the compounds showed higher selectivity towards hepatocellular carcinoma rather than the normal lung fibroblast cell line WI-38. The presence of methyl ester at C-30 greatly increased the cytotoxicity of ME-GA which might be attributed to its higher activity and selectivity. Both ME-GA and AKBA contributed to inhibit cancer cell migration in the wound healing assay and impeded colony formation. The use of flow cytometry to carry out cell cycle analysis and the determination of possible mechanisms of action for apoptosis revealed that ME-GA arrested the cell cycle at G2/M that led to the inhibition of hepatocellular carcinoma and induced apoptosis via the extrinsic pathway and its ability to increase p53 transactivation. Conclusion: This work highlights the cytotoxicity of glycyrrhizin and its derivatives for possible use as a chemotherapeutic agent against hepatocellular carcinoma cells HepG-2. The most cytotoxic compound was ME-GA (18β-Glycyrrhetinic-30-methyl ester) with no cytotoxic effect on the normal cell line. In summary, this new derivative may be used as an alternative or complementary medicine for liver cancer.