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Mechanistic insights into Retama raetam's anti-proliferative and pro-apoptotic effects in A549 lung cancer cells:
Mohammed Ali Alshehri1, Mohamed Ali Seyed2, Chellasamy Panneerselvam1,3
1Department of Biology, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia.
Abstract:
Lung cancer, particularly non-small cell lung cancer (NSCLC), is a leading cause of cancer-related deaths worldwide. This study investigates the molecular mechanisms behind the anti-cancer effects of the tropical desert plant Retama raetam (R. raetam) on the A549 NSCLC cell line. The research examined R. raetam's anti-proliferative effects, cytotoxicity, apoptosis, reactive oxygen species (ROS) generation, mitochondrial membrane potential, and cell morphology in NSCLC A549 and L-132 cells. In addition, the influence of R. raetam on DNA fragmentation, apoptotic signaling, and PI3K/Akt pathways for its anti-cancer mechanism was examined. Our results indicated that R. raetam's effects were dose- and time-dependent to exhibit anti-proliferative effects on A549 cells. R. raetam treatment promoted apoptotic cell death cycle arrest, increased apoptotic cells, depolarized the mitochondrial membrane, and induced morphological alterations in cells and nuclei. It also inhibited A549 cell migration (P < 0.05), colonization, and invasiveness. Moreover, the study demonstrated that R. raetam treatment resulted in the upregulation of Bax expression, downregulation of Bcl-2 expression, and apoptotic fragmented DNA in A549 cells. The top five bioactive compounds derived from R. raetam exhibited molecular interactions that inhibit PIK3CA and AKT1. This inhibition leads to an increased frequency of apoptosis and subsequent death of cancer cells. Additionally, R. raetam extract induced an increase in ROS formation and cytochrome c levels, indicating that its toxic effects on A549 cells involve both ROS-dependent cytotoxicity through the disruption of mitochondrial transmembrane potential ΔΨm and ROS-independent cell cycle arrest through downregulation BCL-2, PARP, E-Cadherin, PI3K, and Akt expressions pathways.
Insights
The tropical desert plant Retama raetam (R. raetam) exhibits anti-cancer properties against non-small cell lung cancer (NSCLC). R. raetam induces cancer cell death through apoptosis and disruption of key signaling pathways.
Area of Science:
- Phytochemistry
- Molecular Biology
- Cancer Research
Background:
- Non-small cell lung cancer (NSCLC) remains a significant global health challenge, driving the search for novel therapeutic agents.
- Natural products, like the desert plant Retama raetam (R. raetam), offer a promising avenue for discovering new anti-cancer compounds.
- Understanding the molecular mechanisms of plant-derived compounds is crucial for developing effective cancer treatments.
Purpose of the Study:
- To investigate the anti-cancer mechanisms of Retama raetam (R. raetam) extract on A549 non-small cell lung cancer (NSCLC) cells.
- To evaluate the effects of R. raetam on cancer cell proliferation, apoptosis, migration, and invasion.
- To elucidate the role of reactive oxygen species (ROS) and specific molecular pathways (PI3K/Akt) in R. raetam's anti-cancer activity.
Main Methods:
- Treatment of A549 NSCLC cells with varying doses and incubation times of R. raetam extract.
- Assessment of cell viability, apoptosis markers (Bax, Bcl-2, DNA fragmentation), mitochondrial membrane potential, and ROS generation.
- Analysis of cell morphology, migration, invasion, and key signaling pathway proteins (PI3K, Akt, PARP, E-Cadherin).
Main Results:
- R. raetam demonstrated dose- and time-dependent anti-proliferative and cytotoxic effects on A549 cells.
- Treatment induced apoptosis, cell cycle arrest, and morphological changes, while inhibiting cell migration and invasion.
- R. raetam upregulated Bax, downregulated Bcl-2, fragmented DNA, increased ROS and cytochrome c, and inhibited PI3K/Akt signaling pathways.
Conclusions:
- Retama raetam possesses significant anti-cancer potential against NSCLC by inducing apoptosis and inhibiting cell proliferation and metastasis.
- The anti-cancer effects are mediated through both ROS-dependent mechanisms (disrupting mitochondrial potential) and ROS-independent pathways (cell cycle arrest via PI3K/Akt inhibition).
- Bioactive compounds in R. raetam show promise for the development of novel NSCLC therapeutics.
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