a Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.
b Children's Cancer Hospital Egypt 57357, Cairo, Egypt.
Biochem Cell Biol. 2019 Aug;97(4):437-445. doi: 10.1139/bcb-2018-0318. Epub 2019 Jan 3.
This study evaluated the antitumor activity of a methanolic extract from the leaves of (ZSCL) against diethylnitrosamine (DENA)-induced hepatocarcinoma in rats. The phytochemical constituents, in vitro antioxidant and cytotoxic activities of ZSCL extract were investigated. Male Wistar rats were distributed among 6 groups: () normal control; () ZSCL1-treated rats (100 mg/kg body mass; "b.m."); () ZSCL2-treated rats (300 mg/kg b.m.); () rats with DENA-induced hepatocarcinoma; ( and ) rats with hepatocarcinoma that were treated with either () ZSCL1 or () ZSCL2. Serum liver function and levels of oxidative stress were assayed. The expression of hepatocyte growth factor, insulin-like growth factor-1 receptor, B cell lymphoma-2, and matrix metalloproteinase-9 oncogenes were quantified in liver samples. Histological examination of the liver tissues was performed. The ZSCL was rich in essential fatty acids, phytol, and polyphenolic flavones (luteolin and quercetin) with strong free-radical and peroxide scavenging activities and cytotoxic activity. Administration of ZSCL1 and ZSCL2 to the rats produced no toxic effects. DENA induced hepatocellular carcinoma and cholangioma by producing oxidative stress and upregulating the expression of hepatic oncogenes. Treatment of DENA-induced hepatocarcinoma with ZSCL2 ameliorated all of the abnormalities induced by DENA except for cholangioma. In conclusion, the ZSCL (300 mg/kg b.m.) displayed strong therapeutic activity against DENA-induced hepatocellular carcinoma via targeting oxidative stress and oncogenes.
本研究评估了从 （ZSCL）叶中提取的甲醇提取物对二乙基亚硝胺（DENA）诱导的大鼠肝癌的抗肿瘤活性。研究了 ZSCL 提取物的植物化学成分、体外抗氧化和细胞毒性活性。雄性 Wistar 大鼠分为 6 组：（）正常对照组；（）ZSCL1 处理组（100mg/kg 体重；“b.m.”）；（）ZSCL2 处理组（300mg/kg b.m.）；（）DENA 诱导的肝癌大鼠；（和）用（）ZSCL1 或（）ZSCL2 治疗的肝癌大鼠。测定血清肝功能和氧化应激水平。定量测定肝组织中肝细胞生长因子、胰岛素样生长因子-1 受体、B 细胞淋巴瘤-2 和基质金属蛋白酶-9 癌基因的表达。对肝组织进行组织学检查。ZSCL 富含必需脂肪酸、叶绿醇和多酚类黄酮（木犀草素和槲皮素），具有很强的自由基和过氧化物清除活性和细胞毒性活性。ZSCL1 和 ZSCL2 给药对大鼠没有产生毒性作用。DENA 通过产生氧化应激和上调肝癌基因的表达诱导肝细胞癌和胆管癌。用 ZSCL2 治疗 DENA 诱导的肝癌可改善 DENA 诱导的除胆管癌以外的所有异常。总之，ZSCL（300mg/kg b.m.）通过靶向氧化应激和癌基因对 DENA 诱导的肝细胞癌显示出强大的治疗活性。
