Shikonin, a natural
naphthoquinone pigment isolated from Lithospermum erythrorhizon, has been reported to suppress growth of various
cancer cells. This study was aimed to investigate whether this chemical could also inhibit cell growth of
lung cancer cells and, if so, works via what molecular mechanism. To fulfill this, A549
lung cancer cells were treated with
shikonin and then subjected to microscopic, biochemical, flow cytometric, and molecular analyses. Compared with the controls,
shikonin significantly induced cell apoptosis and reduced proliferation in a dose-dependent manner. Specially, lower concentrations of
shikonin (1-2.5 μg/mL) cause viability reduction; apoptosis and cellular senescence induction is associated with upregulated expressions of cell cycle- and apoptotic signaling-regulatory
proteins, while higher concentrations (5-10 μg/mL) precipitate both apoptosis and
necrosis. Treatment of cells with
pifithrin-α, a specific inhibitor of p53, suppressed
shikonin-induced apoptosis and premature senescence, suggesting the role of p53 in mediating the actions of
shikonin on regulation of
lung cancer cell proliferation. These results indicate the potential and dose-related cytotoxic actions of
shikonin on A549
lung cancer cells via p53-mediated cell fate pathways and raise
shikonin a promising adjuvant chemotherapeutic agent for treatment of
lung cancer in clinical practice.