Al-Oqail Mai Mohammad
Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia.
Saudi Pharm J. 2021 Mar;29(3):244-251. doi: 10.1016/j.jsps.2021.01.008. Epub 2021 Feb 10.
Breast cancer is a growing health issue globally and accounts as a second most cause of mortality. Natural products have been a fundamental of health care for long. Plants derived natural products have gained considerable attention over synthetic medicines, since they are safe and non-toxic. (Dombey) Burdet and B.B. Simpson plant belonging to Krameriaceae family, has been known for its beneficial effects against diseases. Herein, firstly, cytotoxic potential of petroleum ether (KLH), chloroform (KLC), ethyl acetate (KLEA), and ethanolic (KLET) extracts of was screened against MCF-7 cells exposed to 10-1000 μg/mL for 24 h. Secondly, the most cytotoxic extract (KLH) was used to explore the mechanisms of cytotoxicity in MCF-7 cells. MCF-7 cells were treated with KLH at 250-1000 μg/mL to measure the oxidative stress markers (glutathione (GSH) and lipid peroxidation (LPO)) and reactive oxygen species (ROS) generation. Further, loss of mitochondrial membrane potential (MMP) and caspase-3 and -9 enzyme activities were studied. The viability of MCF-7 cells were decreased from 44% to 90% for KLH, from 7% to 71% for KLEA, from 39% to 80% for KLC, and from 3% to 81% for KLET, respectively at 250-1000 μg/mL as observed by MTT assay. An increase of 91% in LPO and 2.2-fold in ROS generation and a decrease of 59% in GSH and 68% in MMP levels at 1000 μg/mL showed that KLH induced MCF-7 cell death via oxidative stress and elevated level of ROS generation which further leads to mitochondrial membrane dysfunction and activation of caspase enzymes. The findings of this study provide a mechanistic insight on anticancer efficacies of extracts against MCF-7 cells and support the use of it for the treatment of breast cancer diseases.
乳腺癌是全球范围内日益严重的健康问题，是第二大致死原因。长期以来，天然产物一直是医疗保健的基础。源自植物的天然产物比合成药物更受关注，因为它们安全无毒。（唐比）布尔迪特和B.B. 辛普森植物属于刺山柑科，其对疾病的有益作用已为人所知。在此，首先，筛选了石油醚提取物（KLH）、氯仿提取物（KLC）、乙酸乙酯提取物（KLEA）和乙醇提取物（KLET）对暴露于10 - 1000μg/mL 24小时的MCF - 7细胞的细胞毒性潜力。其次，使用细胞毒性最强的提取物（KLH）来探究其在MCF - 7细胞中的细胞毒性机制。用250 - 1000μg/mL的KLH处理MCF - 7细胞，以测量氧化应激标志物（谷胱甘肽（GSH）和脂质过氧化（LPO））以及活性氧（ROS）的产生。此外，还研究了线粒体膜电位（MMP）的丧失以及半胱天冬酶 - 3和 - 9的酶活性。通过MTT法观察到，在250 - 1000μg/mL时，KLH使MCF - 7细胞活力从44%降至90%，KLEA从7%降至71%，KLC从39%降至80%，KLET从3%降至81%。在1000μg/mL时，LPO增加91%，ROS产生增加2.2倍，GSH降低59%，MMP水平降低68%，这表明KLH通过氧化应激诱导MCF - 7细胞死亡，并导致ROS产生水平升高，进而导致线粒体膜功能障碍和半胱天冬酶酶的激活。本研究结果为提取物对MCF - 7细胞的抗癌疗效提供了机制性见解，并支持将其用于治疗乳腺癌疾病。
