Biol. Pharm. Bull. 28(2) 226—232 (2005)

of the antimicrobial anthocyanin red pigment dracorhodin (Fig. 1B), which is isolated in the exudates of the fruit of Daemonorops draco, known as “dragon’s blood” in traditional Chinese medicine and as Kirin-kakketsu in Japanese. It has been used for the treatment of injuries and bleeding. Many flavonoids have been reported to induce apoptosis in human tumor cells, and therefore the cytotoxic effect of dracorhodin perchlorate on human melanoma A375-S2 cells is examined in the present study. Numerous anticancer drugs exert their therapeutic action by inducing apoptosis in various malignant cells. A variety of proteins and genes are involved in apoptosis. Caspases are a family of cysteine proteases that mediate apoptosis. Binding of death ligands such as FasL to their cognate receptors triggers the extrinsic pathway, leading to activation of caspases-8 and -10. Cellular stresses such as UV irradiation result in engagement of the intrinsic cell death pathway leading to procaspase-9 and -2 activation. Both pathways lead to a cascade of executioner caspases (-3, -6, -7), which results in the cleavage of a number of caspase substrates responsible for apoptotic demise of the cells by cleaving intracellular proteins, altering or negating protein functions. The Bcl-2 protein family is a large family of apoptosisregulating proteins that modulate the mitochondrial pathway. It includes both antiapoptotic proteins, such as Bcl-2 and Bcl-XL, and proapoptotic proteins such as Bax and Bak. 12) These proteins regulate mitochondrial membrane permeability, either promoting or suppressing the release of apoptogenic proteins from these organelles. The tumor suppressor p53 plays an important role in regulating the expression of genes that mediate cell cycle arrest and/or apoptosis in response to genotoxic insults. Following environmental insults, p53 is activated by posttranslational modifications such as phosphorylation and acetylation which increase its protein stability and enhance its DNA binding activity. Activated p53 upregulates expression of downstream target genes, including Bax, p53-upregulated modulator of apoptosis (PUMA), and cell-cycle regulator p21, and thus elevated p53 activity results in either cell cycle arrest or direct cell death. The mitogen-activated protein kinases (MAPKs) include extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal protein kinase (JNK), and p38 kinase. ERK is generally considered to be a survival mediator involved in the protective actions of growth factors in apoptosis, whereas p38 and JNK are usually referred to as stress-stimulated MAPKs, which are required for the induction of apoptosis by diverse stimuli such as UV irradiation, oxidants, and anti226 Biol. Pharm. Bull. 28(2) 226—232 (2005) Vol. 28, No. 2