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Evidence-Based Complementary and Alternative Medicine
Volume 2015, Article ID 236159, 8 pages
http://dx.doi.org/10.1155/2015/236159
Research Article

Artocarpin Induces Apoptosis in Human Cutaneous Squamous Cell Carcinoma HSC-1 Cells and Its Cytotoxic Activity Is Dependent on Protein-Nutrient Concentration

1Department of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
2Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
3Division of Basic Medical Sciences, Department of Nursing, Chang Gung Institute of Technology and Chronic Diseases and Health Promotion Research Center, Chiayi, Taiwan
4Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan 33303, Taiwan
5Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung 807, Taiwan
6Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan

Received 5 October 2014; Accepted 1 December 2014

Academic Editor: Didier Stien

Copyright © 2015 Stephen Chu-Sung Hu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.