Siamayuwa Clayton E, Nyanga Loveness K, Chidewe Cathrine
Department of Biochemistry, University of Zimbabwe, P.O. Box MP 167 Mount Pleasant, Harare, Zimbabwe.
Institute of Food and Nutritional Sciences, University of Zimbabwe, P.O. Box MP 167 Mount Pleasant, Harare, Zimbabwe.
Evid Based Complement Alternat Med. 2020 Mar 26;2020:8567182. doi: 10.1155/2020/8567182. eCollection 2020.
(Oliv.) Engl. and contain compounds that have antimutagenic properties. The rise in rhabdomyosarcoma in paediatrics and prognosis of the disease in infants compared to adults calls for newer, less toxic alternatives in treatment of the disease. The aim of this study was to determine the anticancer activity and antioxidant capacity of combined leaf extracts of (Oliv.) Engl. and (SAHA), against rhabdomyosarcoma (RMS) using rhabdomyosarcoma (RD) cell line and mouse (L20B) cell line. Cytotoxicity, morphology, apoptosis induction, and antioxidant capacity assays were done. Of the four solvents used for extraction, the dichloromethane SAHA extract was the most cytotoxic with IC of 106 g/mL after doxorubicin, the reference anticancer drug with IC of 0.8 g/mL. The SAHA extracts had a stronger cytotoxicity effect on the cancerous RD cells than on normal L20B cells. Morphological assessment showed untreated cells maintained their normal striated appearance of muscle cells whereas cells treated with doxorubicin or SAHA extracts exhibited cell shrinkage, loss of surface adherence, reduced cell density along with cell debris, which is a characteristic of apoptosis. Normal L20B cells when treated with doxorubicin or SAHA extracts, maintained their cell shape, and remained adherent to the surface. The apoptotic enzyme caspase-3 was induced in a concentration dependent manner upon treatment of the RD cells with SAHA extracts or doxorubicin. Induction of caspase-3 was ten times less in treated L20B cells compared to the RD cells. Low induction of caspase-9 enzyme was observed in both treated RD and L20B cells. Treatment of both RD and L20B cells with SAHA extracts or doxorubicin resulted in increased activity of peroxidase and reduction of oxidative stress. Results of the study show that the SAHA extracts are potential sources of compounds that may serve as useful agents for treatment of rhabdomyosarcoma.
(奥利弗)恩格勒 且含有具有抗诱变特性的化合物。与成人相比,小儿横纹肌肉瘤的发病率上升以及婴儿该疾病的预后情况,促使人们在该疾病的治疗中寻求更新的、毒性更小的替代方案。本研究的目的是使用横纹肌肉瘤(RD)细胞系和小鼠(L20B)细胞系,确定(奥利弗)恩格勒 和 (SAHA)的联合叶提取物对横纹肌肉瘤(RMS)的抗癌活性和抗氧化能力。进行了细胞毒性、形态学、凋亡诱导和抗氧化能力测定。在所使用的四种提取溶剂中,二氯甲烷SAHA提取物的细胞毒性最强,其IC50为106 μg/mL,仅次于多柔比星(参考抗癌药物,IC50为0.8 μg/mL)。SAHA提取物对癌性RD细胞的细胞毒性作用比对正常L20B细胞更强。形态学评估显示,未处理的细胞保持其正常的肌肉细胞横纹外观,而用多柔比星或SAHA提取物处理的细胞则表现出细胞收缩、表面附着力丧失、细胞密度降低以及细胞碎片,这是凋亡的特征。用多柔比星或SAHA提取物处理正常L20B细胞时,它们保持细胞形状并仍附着于表面。用SAHA提取物或多柔比星处理RD细胞后,凋亡酶半胱天冬酶 - 3以浓度依赖性方式被诱导。与RD细胞相比,处理后的L20B细胞中半胱天冬酶 - 3的诱导量少十倍。在处理后的RD细胞和L20B细胞中均观察到半胱天冬酶 - 9酶的低诱导。用SAHA提取物或多柔比星处理RD细胞和L20B细胞均导致过氧化物酶活性增加和氧化应激降低。研究结果表明,SAHA提取物是可能用作治疗横纹肌肉瘤有用药物的化合物的潜在来源。