Anticancer potential of Ulva lactuca extract: inhibition of growth kinetics and radial invasion in 3D tumor spheroids

Cancer is a leading cause of global mortality, characterized by uncontrolled proliferation and metastasis. Novel therapeutics are necessary to combat this heterogeneous disease. Traditional pre-clinical studies often utilize two-dimensional (2D) cell culture models that do not mimic the complex architecture of human tumors. This study aimed to investigate the anticancer potential of an aqueous extract from the green seaweed Ulva lactuca, specifically focusing on its ability to modulate growth kinetics and restrict radial invasion in a more physiologically relevant three-dimensional (3D) environment. We employed a 3D multicellular tumor spheroid model across three human malignancy lines: HT-29 (colorectal adenocarcinoma), LNCaP (lymph node carcinoma of the prostate), and HT-1080 (fibrosarcoma). Spheroids were treated with and without U. lactuca extract and monitored longitudinally for 14 days. Growth kinetics were characterized using locally estimated scatterplot smoothing (LOESS) regression and area-under-the-curve (AUC) analysis. In addition, a 3D invasion assay was performed using HT-1080 spheroids to quantify the extract’s impact on radial expansion and volumetric infiltration. U. lactuca extract significantly inhibited spheroid expansion across all cell lines, with growth reductions ranging from 20% to 26% (p < 0.001). Longitudinal analysis revealed substantial kinetic delays, with doubling time milestones extended by up to 3.5 days in HT-29 models. In the HT-1080 invasion assay, the extract suppressed invasive area by 42.5% (p < 0.001). Notably, treatment delayed the radial expansion milestone by four days, effectively reducing the invasion burden compared to untreated controls. These findings demonstrate that U. lactuca extract inhibits the proliferative and invasive trajectories of multiple cancer types in 3D models. By significantly altering growth kinetics and restricting radial invasion, this marine-derived extract shows promise as a multi-targeted therapeutic agent against aggressive malignancies.