Hispolon Decreases Melanin Production and Induces Apoptosis in Melanoma Cells through the Downregulation of Tyrosinase and Microphthalmia-Associated Transcription Factor (MITF) Expressions and the Activation of Caspase-3, -8 and -9

Abstract

Hispolon is one of the most important functional compounds that forms Phellinus linteus (Berkeley & Curtis) Teng. Hispolon has antioxidant, anti-inflammatory, antiproliferative and anticancer effects. In this study, we analyzed the functions of hispolon on melanogenesis and apoptosis in B16-F10 melanoma cells. The results demonstrated that hispolon is not an enzymatic inhibitor for tyrosinase; rather, it represses the expression of tyrosinase and the microphthalmia-associated transcription factor (MITF) to reduce the production of melanin in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16-F10 cells at lower concentrations (less than 2 μM). In contrast, at higher concentration (greater than 10 μM), hispolon can induce activity of caspase-3, -8 and -9 to trigger apoptosis of B16-F10 cells but not of Detroit 551 normal fibroblast cells. Therefore, we suggest that hispolon has the potential to treat hyperpigmentation diseases and melanoma skin cancer in the future.

Hispolon suppresses migration and invasion of human nasopharyngeal carcinoma cells by inhibiting the urokinase‐plasminogen activator through modulation of the Akt signaling pathway

“…In addition to an antimetastatic ability via inhibiting the proteolytic activity of ECM proteinases, several studies have reported that hispolon exhibits antitumor ability by inducing cell cycle arrest and apoptosis, such as in melanoma, leukemia, hepatocellular cancer, and gastric cancer (Chen et al, ; Huang et al, ; Chen et al, ; Hsiao et al, ; Chen et al, ). Similarly, in NPC, Hsieh et al, demonstrated that hispolon induced phosphorylation of ERK1/2, JNK1/2, and p38 MAPK pathways, stimulating activation of caspase‐3, ‐8, and ‐9, which eventually induced the apoptosis of HONE‐1 and NPC‐39 cells (Hsieh et al, ).…”

“…Recently, the antitumor effects of this phenolic compound have been demonstrated in the cell lines of various cancers. In addition, several studies have shown that hispolon can induce cell cycle arrest and apoptosis in cancer cells including melanoma, leukemia, hepatocellular cancer, and gastric cancer (Chen et al, , Huang et al, ; Chen et al, ; Hsiao et al, ; Chen et al, ). Furthermore, hispolon has also been shown to inhibit metastasis of hepatoma cells by reducing the expression of MMP‐2, MMP‐9, and uPA through suppression of the PI3K–Akt and ERK signaling pathways (Huang et al, ).…”

Establishment of a melanogenesis regulation assay system using a fluorescent protein reporter combined with the promoters for the melanogenesis-related genes in human melanoma cells

“…The total amount of melanin in each cell suspension was determined by recording the absorbance at 405 nm [13].…”

“…The cell-based melanin content assay in mouse melanocytes (e.g., B16F10 mouse melanoma cells) is better than the mushroom tyrosinase activity assay because it provides more credible results http://dx.doi.org/10.1016/j.enzmictec.2014.09.008 0141-0229/© 2014 Elsevier Inc. All rights reserved. [13,14]. However, this assay is time-consuming, requiring approximately 3-5 days to complete.…”

Hispolon as an inhibitor of TGF-β-induced epithelial-mesenchymal transition in human epithelial cancer cells by co-regulation of TGF-β-Snail/Twist axis

“…In addition, HPL has demonstrated antitumor effects in various types of cancer cells, including melanoma, leukemia, hepatocarcinoma, bladder cancer and gastric cancer cells (16)(17)(18)(19)(20).…”