title: Antioxidant and antitumor activities of Capparis spinosa L. and the related mechanisms.
abstract: The 'ethnodrug' Capparis spinosa L. has several pharmacological activities. First, it was found in previous experiments that an ethyl acetate extract of Capparis spinosa L. (CSE) exhibited antioxidant activity. In order to further research this finding, the present study investigate the blood biochemical indices, injury, energy metabolism, oxidative damage and mitochondrial membrane potential (Δψm) level of cardiac cells to study the effect of CSE on doxorubicin-induced cardiac toxicity. CSE had protective effects on the cardiac toxic effect of doxorubicin, and decreased the activity of lactic dehydrogenase (LDH) and creatine kinase (CK). CSE increased the ability of myocardial tissue to scavenge free radicals, inhibited lipid peroxidation, increased recovery activity of antioxidant enzymes, adjusted the energy metabolism of myocardial tissue, inhibited the generation of a large number of ROS in the cells, raised the level of Δψm, and improved the metabolism of free radicals. CSE demonstrated protective effects on doxorubicin-induced myocardial damage. Second, the quaternary ammonium hydroxide of Capparis spinosa L. (CSQAH) was found to possess antitumor activity, such as antiproliferative and apoptosis-induced effects on HepG2 cells. We investigated the regulatory mechanism of HepG2 apoptosis induced by CSQAH. Laser scanning confocal microscope and Fluo-3/AM staining were utilized to detect the Ca2+ concentration in the HepG2 cells. A microplate reader was used to measure the changes in Ca2+-Mg2+-ATP enzyme. Then, flow cytometry was applied to analyze the activity of ROS and the expression levels of Bcl-2 and Bax. As a result, different concentrations of CSQAH increased the concentration of Ca2+ in the cytoplasm in a dosage-dependent manner. CSQAH decreased the Ca2+‑Mg2+‑ATPase activity in the HepG2 cells. The levels of ROS in the CSQAH groups were significantly higher than the level in the control group. Flow cytometric analysis showed that the Bcl-2 expression levels in the CSQAH-treated groups were downregulated, while Bax expression levels were upregulated, and the effects were dosage-dependent. The regulatory mechanism of HepG2 cell apoptosis induced by CSQAH involved the increase in Ca2+ concentration and ROS levels, a decrease in Ca2+-Mg2+-ATPase activity in the HepG2 cells, and downregulation of anti-apoptotic Bcl-2 expression, and upregulation of apoptotic Bax expression. In summary, the present study demonstrated the antioxidant and antitumor activities of CSE which may suppress tumor growth and alleviate the side-effects of DOX, which may facilitate tumor treatment in a dual manner.
authors.affiliation: Center of Research and Development on Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin 150076, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: Center of Research and Development on Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin 150076, P.R. China.
authors.forename: Jinghui
authors.initials: J
authors.lastname: Yang
authors.affiliation: Center of Research and Development on Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin 150076, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Center of Research and Development on Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin 150076, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Center of Research and Development on Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin 150076, P.R. China.
authors.forename: Yongxue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Center of Research and Development on Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin 150076, P.R. China.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Ji
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D031484:Capparis / Q000737:chemistry*; D004317:Doxorubicin / Q000009:adverse effects*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; C494826:BAX protein, human; D020011:Protective Agents; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D004317:Doxorubicin; D017301:Ca(2+) Mg(2+)-ATPase