Seglab Fatiha, Abou Assali Mazen, AlYafei Thoraya, Hassan Hassan, Pinto Diana C G A, Baydoun Safaa, Al Thani Asmaa A, Shaito Abdullah A
Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar.
Environmental Science Center, Qatar University, Doha P.O. Box 2713, Qatar.
Biology (Basel). 2024 Sep 2;13(9):687. doi: 10.3390/biology13090687.
is a widely used plant in traditional Mediterranean and Middle Eastern medicine for various illnesses. has been shown to have anticancer effects against various cancers, but its effects against lung cancer have been under limited investigation. At the same time, is rich in terpenoids whose anti-lung cancer effects have been poorly investigated. This study aimed to examine the potential anticancer properties of methanolic and aqueous extracts of stems and leaves of and its terpenoid-rich fraction against human lung cancer A549 cells. Results showed that the methanolic extracts of had significantly higher polyphenol and flavonoid content and radical scavenging capacity than the aqueous extracts. In addition, leaves methanolic extracts (IVLM) caused the highest reduction in viability of A549 cells among all the extracts. IVLM also reduced the viability of human ovarian SK-OV-3, breast MCF-7, liver HepG2, and colorectal HCT116 cancer cells. A terpenoid-rich fraction (IVL DCM), prepared by liquid-liquid separation of IVLM in dichloromethane (DCM), displayed a substantial reduction in the viability of A549 cells (IC = 27.8 ± 1.5 µg/mL at 48 h) and the panel of tested cancerous cell lines but was not cytotoxic to normal human embryonic fibroblasts (HDFn). The assessment of IVL DCM phytochemical constituents using GC-MS analysis revealed 21 metabolites, highlighting an enrichment in terpenoids, such as lupeol and its derivatives, caryophyllene oxide, betulin, and isopulegol, known to exhibit proapoptotic and antimetastatic functions. IVL DCM also showed robust antioxidant capacity and decent polyphenol and flavonoid contents. Furthermore, Western blotting analysis indicated that IVL DCM reduced proliferation (reduction of proliferation marker Ki67 and induction of proliferation inhibitor proteins P21 and P27), contaminant with P38 MAP kinase activation, and induced the intrinsic apoptotic pathway (P53/BCL2/BAX/Caspase3/PARP) in A549 cells. IVL DCM also reduced the migration of A549 cells, potentially by reducing FAK activation. Future identification of anticancer metabolites of IVL DCM, especially terpenoids, is recommended. These data place as a new resource of herbal anticancer agents.
是传统地中海和中东医学中广泛用于治疗各种疾病的植物。已显示出对多种癌症具有抗癌作用，但其对肺癌的作用研究有限。同时，富含萜类化合物，其对肺癌的作用研究较少。本研究旨在研究该植物茎叶的甲醇提取物和水提取物及其富含萜类化合物的部分对人肺癌A549细胞的潜在抗癌特性。结果表明，该植物的甲醇提取物比水提取物具有更高的多酚和黄酮含量以及自由基清除能力。此外，在所有提取物中，叶甲醇提取物（IVLM）导致A549细胞活力下降最多。IVLM还降低了人卵巢SK-OV-3、乳腺MCF-7、肝脏HepG2和结肠直肠HCT116癌细胞的活力。通过在二氯甲烷（DCM）中对IVLM进行液-液分离制备的富含萜类化合物的部分（IVL DCM），显示出A549细胞活力大幅下降（48小时时IC = 27.8±1.5μg/mL）以及受试癌细胞系的活力下降，但对正常人胚胎成纤维细胞（HDFn）没有细胞毒性。使用GC-MS分析对IVL DCM的植物化学成分进行评估，发现了21种代谢物，突出了萜类化合物的富集，如羽扇豆醇及其衍生物、氧化石竹烯、桦木醇和异蒲勒醇，已知它们具有促凋亡和抗转移功能。IVL DCM还显示出强大的抗氧化能力以及相当的多酚和黄酮含量。此外，蛋白质印迹分析表明，IVL DCM降低了A549细胞的增殖（增殖标志物Ki67减少以及增殖抑制蛋白P21和P27的诱导），伴有P38 MAP激酶激活，并诱导了A549细胞的内在凋亡途径（P53/BCL2/BAX/Caspase3/PARP）。IVL DCM还可能通过降低FAK激活来减少A549细胞的迁移。建议未来鉴定IVL DCM的抗癌代谢物，尤其是萜类化合物。这些数据表明该植物是草药抗癌剂的新来源。
