Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2011, Article ID 129045, 11 pages doi:10.1155/2011/129045 Research Article The Efficacy of Dandelion Root Extract in Inducing Apoptosis in Drug-Resistant Human Melanoma Cells S. J. Chatterjee, 1 P. Ovadje, 1 M. Mousa, 1 C. Hamm, 2 and S. Pandey 1 1 Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset Avenue, Windsor, ON, Canada N9B 3P4 2 Windsor Regional Cancer Centre, 2220 Kildare Road, Windsor, ON, Canada N8W 2X3 Correspondence should be addressed to S. Pandey, spandey@uwindsor.ca Received 22 June 2010; Revised 12 November 2010; Accepted 8 December 2010 Copyright © 2011 S. J. Chatterjee 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. Notoriously chemoresistant melanoma has become the most prevalent form of cancer for the 25–29 North American age demographic. Standard treatment after early detection involves surgical excision (recurrence is possible), and metastatic melanoma is refractory to immuno-, radio-, and most harmful chemotherapies. Various natural compounds have shown efficacy in killing different cancers, albeit not always specifically. In this study, we show that dandelion root extract (DRE) specifically and effectively induces apoptosis in human melanoma cells without inducing toxicity in noncancerous cells. Characteristic apoptotic morphology of nuclear condensation and phosphatidylserine flipping to the outer leaflet of the plasma membrane of A375 human melanoma cells was observed within 48 hours. DRE-induced apoptosis activates caspase-8 in A375 cells early on, demonstrating employment of an extrinsic apoptotic pathway to kill A375 cells. Reactive Oxygen Species (ROS) generated from DRE-treated isolated mitochondria indicates that natural compounds in DRE can also directly target mitochondria. Interestingly, the relatively resistant G361 human melanoma cell line responded to DRE when combined with the metabolism interfering antitype II diabetic drug metformin. Therefore, treatment with this common, yet potent extract of natural compounds has proven novel in specifically inducing apoptosis in chemoresistant melanoma, without toxicity to healthy cells. 1. Introduction Melanoma skin cancer is among one of the leading cancers targeting adolescents and young adults in the North America. Melanoma is notoriously chemo-resistant and the modes of treatment for melanoma are very limited, relying mainly on surgical excision of the primary site during early detection, and whatever limited chemotherapy and immunotherapy for metastasized melanoma that is available. However, these therapies have limited success and incur side effects [1]. Taraxacum Officinale is most commonly known as dan- delion. Regarded as a regular garden weed, this detoxifying herb has long been used in traditional Chinese medicine, for ailments ranging from digestive disorders to complex disorders such as uterine, breast and lung tumours [2]. Traditional Middle Eastern remedies require dandelions for spleen and liver ailments, while Native Americans have harnessed their properties to cure indigestion, heartburn, and kidney disease [2, 3]. Dandelion plants were (Taraxacum officinale Weber ex Wiggers) were used by East Indians in the 16 century as a hepatic stimulant, diuretic, for liver disorders, and most interestingly, for chronic skin diseases [4, 5]. These roots are a source of triterpenes and steroids [4, 6]. Hata et al. found that upon screening a variety of compounds from wild plants, Taraxacum Officinale was an effective inducer of differentiation in mouse melanoma cells. Furthermore, this group found that one constituent of Chinese dandelion, Lupeol-a triterpene, up-regulated melanogenesis and decreased cell proliferation in mouse melanoma [7]. This triterpene is regarded as cytostatic and not cytotoxic. In another study, skin tumours were promoted in vivo in mice through a two-stage chemical carcinogenesis and treated with water and methanol extracts of Taraxacum japonicum. This showed inhibition of tumour initiation and promotion at both carcinogenesis stages, and it was concluded that Taraxacum, and more specifically taraxasterol (a triterpenoid), is a worthy chemopreventative agent [8, 9]. More recently, Jeon et al. have shown that ethanolic Taraxacum Officinale extracts and derivative forms thereof reduce levels of reactive oxygen species (ROS) and nitric oxide production (NO) and inhibit COX-2 expression or its antioxidant activity, thus making dandelion extracts