Open Access

ARTICLE

Comparative Anticancer Mechanisms of Viscum album var. coloratum Water Extract and Its Lectin on Primary and Metastatic Melanoma Cells

Chang-Eui Hong¹, Su-Yun Lyu^2,*

1 Department of Pharmacy, Sunchon National University, Suncheon, 57922, Republic of Korea
2 Institute of Life and Pharmaceutical Sciences, Sunchon National University, Suncheon, 57922, Republic of Korea

* Corresponding Author: Su-Yun Lyu. Email:

(This article belongs to the Special Issue: Innovative Approaches in Cancer and Immunology: Advances in 2D and 3D Cell Models)

BIOCELL 2025, 49(2), 289-314. https://doi.org/10.32604/biocell.2025.061334

Received 22 November 2024; Accepted 05 February 2025; Issue published 28 February 2025

Abstract

Objectives: Among cutaneous malignancies, melanoma stands out for its particularly aggressive nature, with therapeutic interventions becoming notably limited once the disease progresses. In this research, we investigate the tumor-suppressing capabilities of water-extracted Korean mistletoe (Viscum album var. coloratum) and its purified lectin component (V. album var. coloratum agglutinin, VCA) using two distinct mouse melanoma models: B16BL6 and B16F10 cell lines. Methods: The impact of water extract and VCA treatments on melanoma cells was assessed through multiple experimental approaches, examining cellular survival rates, programmed cell death pathways, multicaspase activity, and cell cycle distribution patterns. To elucidate the interconnections among various cellular responses, we employed a suite of statistical techniques encompassing correlation studies, principal component analysis (PCA)-based dimensionality reduction, and dendrogram-based clustering methodologies. Results: The water extract exhibited dose-dependent cytotoxicity with IC₅₀ values of 372.3 ± 8.7 μg/mL and 202.5 ± 8.4 μg/mL for B16BL6 and B16F10 cells, respectively. VCA showed more significant effects, with IC₅₀ values of 0.1992 ± 0.0041 and 0.1981 ± 0.0098 μg/mL for B16BL6 and B16F10 cells, respectively. Both agents induced substantial apoptosis with a significant progression from early to late apoptotic stages, reaching up to 59.4% total apoptotic cells for VCA treatment. This was confirmed by strong multicaspase activation, particularly in VCA-treated cells (up to 88.4% caspase-positive cells). The water extract showed modest effects on cell cycle distribution, with increases in G0/G1 phase (74.6%) in B16BL6 cells and S phase (19.2%) in B16F10 cells, while VCA treatment resulted in G2/M phase reduction (10.0%) in B16F10 cells. Correlation analysis revealed strong negative associations between cell viability and caspase activity (r = −0.843 to −0.878), while hierarchical clustering demonstrated distinct response patterns between low and high concentrations of both agents. Effect size analysis confirmed strong treatment impacts on cell viability (d = −5.89 to −6.12) and caspase activation (d = 3.45 to 5.23). Conclusion: These findings suggest that Korean mistletoe water extract and its isolated lectin may affect both primary and metastatic melanoma cells through distinct mechanisms, demonstrating particular potency in caspase-dependent apoptosis induction. Our findings establish a robust foundation for developing novel therapeutic interventions derived from natural compounds to combat malignant melanoma with high metastatic potential.

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