Tabassum Misbah, Lone Bashir Ahmad, Bhat Mudasir Nazir, Bhushan Anil, Banjare Nagma, Manrique Esteban, Gupta Prasoon, Mondhe Dilip M, Gupta Prem N
Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
ACS Omega. 2023 Aug 23;8(35):31914-31927. doi: 10.1021/acsomega.3c03649. eCollection 2023 Sep 5.
Natural product-derived molecules exhibit potential as anticancer agents. Trilliumoside A, a new steroidal saponin, was obtained from rhizomes of , and its anticancer activity was investigated in the presented study. Trilliumoside A was investigated in a panel of cell lines, and it exhibited promising cytotoxic activity on the A549 cells (human lung cancer cells) with an IC of 1.83 μM. The mechanism of cell death induced by Trilliumoside A in A549 cells and its anticancer potential in murine tumor models (EAC and EAT) were presented in the current research. Trilliumoside A was found to induce apoptosis in A549 cells by increasing the expression of various apoptotic proteins, such as Bax, Puma, cytochrome C, cleaved PARP, and cleaved caspase 3. Additionally, Trilliumoside A regulates the expression of p53, CDK2, and Cyclin A by decreasing the mitochondrial membrane potential, elevating reactive oxygen species, and stopping the growth of A549 cells in the synthesis phase (S) of the cell cycle. Trilliumoside A showed a considerable reduction in the tumor volume, the amount of ascitic fluid, and the total cell number without affecting the body weight of animals. Our results demonstrate that Trilliumoside A inhibits the proliferation of human lung cancer cells by inducing DNA damage, arresting the cell cycle, and activating the mitochondrial signaling pathway. The study demonstrated the potential of Trilliumoside A as a potential anticancer agent.
天然产物衍生分子具有作为抗癌剂的潜力。从延龄草的根茎中获得了一种新的甾体皂苷——延龄草苷A,并在本研究中对其抗癌活性进行了研究。在一组细胞系中对延龄草苷A进行了研究,它对A549细胞(人肺癌细胞)表现出有前景的细胞毒性活性,IC50为1.83μM。本研究阐述了延龄草苷A在A549细胞中诱导细胞死亡的机制及其在小鼠肿瘤模型(艾氏腹水癌和艾氏实体癌)中的抗癌潜力。发现延龄草苷A通过增加各种凋亡蛋白的表达,如Bax、Puma、细胞色素C、裂解的PARP和裂解的半胱天冬酶3,诱导A549细胞凋亡。此外,延龄草苷A通过降低线粒体膜电位、升高活性氧物种以及阻止A549细胞在细胞周期的合成期(S期)生长,来调节p53、CDK2和细胞周期蛋白A的表达。延龄草苷A使肿瘤体积、腹水量和总细胞数显著减少,而不影响动物体重。我们的结果表明,延龄草苷A通过诱导DNA损伤、阻滞细胞周期和激活线粒体信号通路来抑制人肺癌细胞的增殖。该研究证明了延龄草苷A作为一种潜在抗癌剂的潜力。