Enhanced Anti-cancer Effects of Conditioned Medium From Hypoxic Cultured Human Adult Dermal Fibroblasts

This study investigates the anti-cancer effects of cervical cancer (HeLa) cells in a conditioned medium (CM) obtained from normoxic and hypoxic cultured human adult dermal fibroblasts (HDFs). The HeLa cells showed decreased cell viability, arrested cell cycles, and increased apoptosis in CM from hypoxic cultured HDFs (H-CM) compared with normoxic cultured HDFs (N-CM). In up-regulated (> 2-fold) proteins of H-CM compared with N-CM, the top enriched term of biological process of gene ontology (GO) was GO:0006955~immune response. In intracellular down-regulated (> 2-fold) proteins of HeLa cells treated with H-CM compared with N-CM, the top enriched term of biological process of GO was GO:0016579~protein deubiquitination, and the terms of the KEGG pathway were determined to be hsa05166:HTLV-I infection, hsa03410:base-excision repair, and hsa05340:primary immunodeficiency. Among down-regulated hub proteins with ≥ 5 edges (ESR1 MCL1, TBP, CD19, LCK, PCNA, CHEK1, and POLA1) of HeLa cells treated with H-CM, the top enriched term of biological process of GO and the KEGG pathway were GO:0006272~leading strand elongation and hsa05166:HTLV-I infection. H-CM displayed not only enhanced anti-cancer effects on HeLa cells compared with N-CM, but also induced intracellular signaling patterns with 9 hub proteins.