Compound K-enriched Korean red ginseng prevents lung cancer progression by targeting cancer cells and fibroblasts.

BACKGROUND: Despite the efficacy of anticancer drugs, patients frequently experience relapse, metastasis, and resistance. A promising therapeutic approach not only targets cancer cell growth but also modulates cancer-associated fibroblasts, which support malignancies. Compound K (CK), a metabolite derived from red ginseng, has demonstrated anticancer properties. Recently, we developed a CK-enriched red ginseng extract (CKP) and explored its potential to suppress lung cancer by inhibiting cancer cell proliferation and inactivating fibroblasts. METHODS: To evaluate the in vitro efficacy of CKP in inhibiting lung cancer cell proliferation, MTT and colony formation assays were performed. The apoptotic effects of CKP on lung cancer cells were assessed using Western blot and flow cytometry. Furthermore, the ability of CKP to inhibit TGF β1-induced migration of cancer cells was investigated through Western blot, RT-PCR, and a wound healing assay. Additionally, the impact of CKP on lung fibroblast inactivation was examined via Western blot and RT-PCR analysis. For in vivo experiments, a xenograft model was utilized, incorporating a combination of lung cancer cells and lung fibroblasts in xenografts. RESULTS: CKP significantly reduced the proliferation and invasiveness of TGF-β1-stimulated A549 cells, demonstrating its potential to inactivate lung fibroblasts. Additionally, CKP inhibited the secretion of cytokines, such as interleukin-6, interleukin-8, and TGF-β1, by activated fibroblasts. In vivo, CKP markedly inhibited tumor growth in the xenograft model. CONCLUSION: In conclusion, CKP effectively induced apoptosis in lung cancer cells, suppressed metastasis, and inactivated fibroblasts, thereby preventing cancer invasion and reducing extracellular matrix production, highlighting its potential as a novel anticancer agent.