Apoptosis Induction and MAPK Pathway Modulation by Lagerstroemia floribunda in Melanoma: Experimental and Computational Insights
摘要
Melanoma, an aggressive skin cancer, leads to over 10,000 deaths annually, necessitating novel therapeutic approaches. Lagerstroemia floribunda (LF), a plant rich in phenolics and flavonoids, has been traditionally used in East Asia for its anticancer properties. This study investigates the biochemical and anti-melanoma effects of LF methanol extracts in B16-F10 melanoma cells. Antioxidant activity was evaluated through total phenolic and flavonoid content, SOD scavenging (IC₅₀ = 181.9 µg/mL), and ORAC assay (15.034 ± 4.405 µmol TE/g). The extract inhibited melanoma cell proliferation by 35.1% at 200 µg/mL, reduced colony formation (30%), and suppressed migration (21.32%). Mechanistically, LF extract disrupted MAPK signaling, decreasing phosphorylation of JNK (30%), ERK1/2 (23%), and p38 (14%). Cell cycle analysis revealed G2/M arrest, while apoptosis induction (98.5% at 100 µg/mL) was mediated by Bax upregulation (2.5-fold) and caspase-3/-9 activation (2-fold and 2.3-fold, respectively). Molecular docking identified quercetin, a major LF compound, as a potent binder to JNK (− 7.505 kcal/mol), p38 (− 7.903 kcal/mol), and Bax (− 5.753 kcal/mol), supporting its role in MAPK inhibition and apoptosis. These findings highlight LF’s ability to modulate key oncogenic pathways and induce programmed cell death in melanoma cells. Given its traditional use and demonstrated bioactivity, LF presents a promising source of bioactive compounds for melanoma treatment, aligning with biotechnological applications in natural product-based drug discovery.