Anticancer potential of β-isopropylfuran-1,2-naphthoquinone in different types of tumor cell lines

Cancer is a multifactorial disease characterized by uncontrolled cell growth and remains a major global health challenge. Given the limitations of conventional therapies, naturally derived compounds such as naphthoquinones have attracted interest for their antitumor potential. This study evaluated the in vitro effects of β-isopropylfuran-1,2-naphthoquinone (NAF-Q69), a synthetic isolapachol derivative, on different cell lines (MRC-5 – human lung fibroblasts; HEPG2 – hepatocellular carcinoma; HeLa – cervical cancer; TOV – ovarian adenocarcinoma; MDA-MB – breast adenocarcinoma; and J82 – urothelial carcinoma) to assess its cytotoxic activity and cellular characteristics (clonogenic survival, migration, morphology, cell cycle, and reactive oxygen species \[ROS] production). NAF-Q69 showed significant dose-dependent cytotoxicity in all tumor lines, with IC50 values ranging from 10.29 µM (MDA-MB) to 18.65 µM (HEPG2). It decreased viability, inhibited colony formation, and impaired migration, particularly in TOV, HeLa, and HEPG2 cells. Morphological alterations were evident. The compound induced cell death, with increased sub-G1 populations, and promoted G2/M arrest. Moreover, NAF-Q69 markedly elevated ROS levels, implicating oxidative stress as a central mechanism. In conclusion, NAF-Q69 exhibits promising antitumor activity by inhibiting proliferation and migration, inducing cell death, and enhancing oxidative stress, supporting the potential of naphthoquinones in cancer therapy.