Pharmacological evaluation of 1-acetyl-β-carboline, a naturally occurring compound with anti-skin cancer potential

The human microbiome comprises microbial communities that reside in the human body and contribute to host health through molecular mediators. <i>Lactobacillus</i> spp. are frequently used as probiotics to restore microbial balance, and <i>L. gasseri</i> has been reported to exert a wide range of beneficial effects. In this study, 1-acetyl-β-carboline (ABC) was identified in <i>L. gasseri</i> cultures and subsequently synthesized via the Pictet-Spengler reaction followed by palladium-catalyzed oxidation. ABC exhibited significant anticancer activity by reducing colony formation and growth of epidermal growth factor-induced JB6 cells and by inhibiting the proliferation of SK-MEL-5 and SK-MEL-28 melanoma cells. Mechanistic studies revealed that ABC induced G2/M phase cell-cycle arrest and promoted apoptosis by regulating related markers, including p27 and caspases-3 and -7. Additionally, ABC significantly inhibited the mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signaling pathway by reducing phosphorylated MEK and phosphorylated ERK levels. ABC also downregulated cyclooxygenase-2 expression, targeting inflammation-related pathways in melanoma cells. In a mouse model, ABC effectively mitigated 12-<i>O</i>-tetradecanoylphorbol-13-acetate (TPA)-induced epidermal hyperplasia and reduced inflammation. These findings highlight the pharmacological significance of ABC, independent of its origin, and suggest that this naturally occurring compound possesses preventive and therapeutic potential against skin cancer.