Department of Pharmacology, National Institute for Pharmaceutical Research and Development, Abuja, Nigeria.
Department of Pharmaceutical Sciences, School of Pharmacy, Cedarville University, Cedarville, Ohio, United States.
Anticancer Agents Med Chem. 2021;21(18):2512-2519. doi: 10.2174/1871520621666210223094235.
Medicinal plants serve as sources of compounds used to treat other types of cancers. The root of the plant Lophira alata (Ochnaceae) has been used as a component of traditional herbal decoctions administered to cancer patients in southwestern Nigeria. However, the mechanism of the cytotoxic effects of Lophira alata alone or in the presence of phorbol ester has not been investigated in brain tumor cells.
This study aimed to examine the cytotoxic potential of the methanolic fraction of Lophira alata root on malignant glioma invasive cellular growth and survival.
The methanolic fraction of Lophira alata (LAM) was subjected to high-performance liquid chromatography to determine the fingerprints of the active molecules. The antiproliferative effects of Lophira alata were assessed using the MTT and LDH assays. Protein immunoblots were carried out to test the effects of Lophira alata, alone or in the presence of phorbol ester, on survival signaling pathways, such as Akt, mTOR, and apoptotic markers such as PARP and caspases.
The methanolic fraction of Lophira alata (LAM) induced a concentration-dependent and time-dependent decrease in glioma cell proliferation. In addition, LAM attenuated phorbol ester-mediated signaling of downstream targets such as Akt/mTOR. Gene silencing using siRNA targeting PKC-alpha attenuated LAM-mediated downregulation of Akt. In addition, LAM induced both PARP and caspase cleavages. The HPLC fingerprint of the fraction indicates the presence of flavonoids.
LAM decreases cell proliferation and induces apoptosis in glioma cell lines and thus could serve as a therapeutic molecule in the management of gliomas.
药用植物是用于治疗其他类型癌症的化合物的来源。植物蓝果树的根（铁青树科）已被用作传统草药汤剂的成分，用于治疗尼日利亚西南部的癌症患者。然而，蓝果树单独或在佛波酯存在下的细胞毒性作用机制尚未在脑肿瘤细胞中进行研究。
本研究旨在研究蓝果树根甲醇提取物对恶性神经胶质瘤侵袭性细胞生长和存活的细胞毒性潜力。
对蓝果树（Lophira alata）的甲醇提取物（LAM）进行高效液相色谱分析，以确定活性分子的指纹图谱。使用 MTT 和 LDH 测定法评估蓝果树的抗增殖作用。通过蛋白免疫印迹检测蓝果树对 Akt、mTOR 等存活信号通路以及 PARP 和 caspase 等凋亡标记物的影响，单独或与佛波酯一起。
蓝果树（LAM）的甲醇提取物诱导神经胶质瘤细胞增殖呈浓度依赖性和时间依赖性下降。此外，LAM 减弱了佛波酯介导的 Akt/mTOR 下游靶标的信号转导。使用针对 PKC-α 的 siRNA 进行基因沉默可减弱 LAM 介导的 Akt 下调。此外，LAM 诱导了 PARP 和 caspase 的切割。该馏分的 HPLC 指纹图谱表明存在类黄酮。
LAM 可降低神经胶质瘤细胞系的细胞增殖并诱导细胞凋亡，因此可作为神经胶质瘤治疗的治疗分子。
