Abstract
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.
Highlights
Lung cancer remains a major challenge to global public health for the high epidemiologic incidence and the oftencatastrophic outcome at the time of diagnosis [1, 2]
Anti-p53 and cytochrome c were purchased from Lab Vision Corp. (Fremont, CA, USA) and anti-α tubulin antibodies from Millipore Corporation (Billerica, MA, USA)
We have for the first time demonstrated that SHK impedes survival and induces apoptosis, necrosis, and senescence of A549 cells in a dose-dependent manner mediated by cytosolic p53
Summary
Lung cancer remains a major challenge to global public health for the high epidemiologic incidence and the oftencatastrophic outcome at the time of diagnosis [1, 2]. Contemporary chemotherapy employing various antineoplastic agents either kills malignant cells incompletely or exerts serious systemic adverse toxicity and fatal organ dysfunction. Studies have shown that a majority of current chemopreventive and therapeutic approaches for lung cancer could potentially prevent or inhibit its development, proliferation, and invasion [3, 4]. Novel antineoplastic agents intervening in mediators regulating expression of genes involved in tumorigenesis, tumor suppression, and DNA repair are under rigorous development [5]. Chemicals that potently inhibit cancer growth through various mechanisms, including apoptosis, necrosis, and premature senescence of Evidence-Based Complementary and Alternative Medicine tumor cells, are under wide survey [6, 7]. Of interest, specified natural herbal medicines proposed promising options for the development of efficient adjuvant chemotherapy for cancer patients [8]
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