title: Artocarpin Induces Apoptosis in Human Cutaneous Squamous Cell Carcinoma HSC-1 Cells and Its Cytotoxic Activity Is Dependent on Protein-Nutrient Concentration.
abstract: Artocarpin, a natural prenylated flavonoid, has been shown to have various biological properties. However, its effects on human cutaneous squamous cell carcinoma (SCC) have not been previously investigated. We set out to determine whether artocarpin has cytotoxic effects on SCC cells and whether its pharmacological activity is dependent on protein-nutrient concentration. Our results showed that treatment of HSC-1 cells (a human cutaneous SCC cell line) with artocarpin decreased cell viability and induced cell apoptosis by increasing caspase 3/7 activity. These effects were more pronounced at low fetal bovine serum (FBS) concentrations. Artocarpin induced an increase in the level of phospho-p38 and a decrease in the levels of phospho-ERK, phospho-JNK, phospho-Akt, phospho-mTOR, and phospho-S6K. High FBS concentrations in the culture media inhibited and delayed the uptake of artocarpin from the extracellular compartment (culture media) into the intracellular compartment, as determined by high performance liquid chromatography (HPLC) analysis. In conclusion, artocarpin induces apoptosis in HSC-1 cells through modulation of MAPK and Akt/mTOR pathways. Binding of artocarpin to proteins in the FBS may inhibit cellular uptake and reduce the cytotoxic activity of artocarpin on HSC-1 cells. Therefore, artocarpin may have potential use in the future as a form of treatment for cutaneous SCC.
authors: Department of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan ; Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors: Stephen Chu-Sung
authors: 0000-0002-1832-4471
authors: SC
authors: Hu
authors: Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors: Chi-Ling
authors: CL
authors: Lin
authors: Department of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Hui-Min
authors: 0000-0002-3573-654X
authors: HM
authors: Cheng
authors: Department of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan ; Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors: Gwo-Shing
authors: GS
authors: Chen
authors: Division of Basic Medical Sciences, Department of Nursing, Chang Gung Institute of Technology and Chronic Diseases and Health Promotion Research Center, Chiayi, Taiwan ; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan 33303, Taiwan.
authors: Chiang-Wen
authors: CW
authors: Lee
authors: Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung 807, Taiwan ; Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors: Feng-Lin
authors: FL
authors: Yen
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