Antioxidative and ROS-dependent apoptotic effects of <i>Cuscuta reflexa</i> Roxb. stem against human lung cancer: network pharmacology and <i>in vitro</i> experimental validation
Creators: name: Elasbali, Abdelbaset Mohamed
name: Abu Al-Soud, Waleed
name: Elayyan, Afnan Elayyan Mousa
name: Alhassan, Hassan H.
name: Danciu, Corina
name: Elfaki, Elyasa Mustafa
name: Alharethi, Salem Hussain
name: Alharbi, Bandar
name: Alanazi, Hamad H.
name: Mohtadi, Mohamed El
name: Patel, Mitesh
name: Adnan, Mohd
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biochemistry
subject: Medicine
subject: Cell Biology
subject: Molecular Biology
subject: Pharmacology
subject: Environmental Sciences not elsewhere classified
subject: Chemical Sciences not elsewhere classified
subject: Ecology
subject: FOS: Biological sciences
subject: Biological Sciences not elsewhere classified
subject: Cancer

description: Lung cancer remains a formidable global health challenge, necessitating the exploration of novel therapeutic approaches. This study investigates the potential of <i>Cuscuta reflexa</i> Roxb. stem extract as an anticancer agent against human lung cancer, focusing on its antioxidative and ROS-dependent apoptotic effects. Utilizing a combination of network pharmacology and in-vitro experimental validation, we delineate the multifaceted molecular mechanisms underlying the observed effects. The antioxidant potential of <i>C. reflexa</i> stem extract was evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH<sup>•</sup>), 2,2-azinobis (3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS<sup>•+</sup>) and ferric reducing/antioxidant power (FRAP), hydroxyl free radical scavenging, reactive nitrogen oxide scavenging and super oxide anion radical scavenging assays. Furthermore, the antiproliferative and proapoptotic effect of <i>C. reflexa</i> stem extract was evaluated against A549 lung adenocarcinoma cell line using the consecrated sulforhodamine B (SBR) and Annexin V-PI assays. Additionally, the mitochondrial membrane potential (MMP) and the total reactive oxygen species (ROS) estimation assays were performed. As a result, network pharmacology analysis revealed a complex interaction network between the bioactive constituents of <i>C. reflexa</i> and key proteins implicated in lung cancer progression. The <i>C. reflexa</i> stem extract showed dose-dependent antioxidant activity against DPPH<sup>•</sup> (IC<sub>50</sub> − 87.38 µg/mL), reactive nitrogen oxide (IC<sub>50</sub> − 318.34 µg/mL), FRAP (IC<sub>50</sub> − 359.96 µg/mL), hydroxy free radicals (IC<sub>50</sub> − 526.12 µg/mL) than ABTS<sup>●+</sup> (IC<sub>50</sub> − 698.45 µg/mL) and super oxide anion (IC<sub>50</sub> − 892.71 µg/mL) as well as cytotoxic activity against A549 cells (IC<sub>50</sub> − 436.80 µg/mL). Observations of morphological features in treated cells have revealed hallmark of apoptosis properties. Furthermore, as a result of treatment with <i>C. reflexa</i> stem extract, ROS generation and mitochondrial depolarization were increased in A549 cells, suggesting that this treatment has significant apoptotic properties. . These findings highlight the potential utility of this natural extract as an innovative therapeutic strategy for lung cancer treatment. The integration of network pharmacology and experimental validation enhances our understanding of the underlying mechanisms and provide the way for further translational research. Communicated by Ramaswamy H. Sarma