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The Growth Inhibitory Effect on B16F10 Melanoma Cells by 4-BPCA, an Amide Derivative of Caffeic Acid

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Author(s)
박유경강신웅이진호장병철
Keimyung Author(s)
Jang, Byeong Churl
Department
Dept. of Molecular Medicine (분자의학)
Journal Title
Keimyung Med J
Issued Date
2022
Volume
41
Issue
1
Keyword
4-BPCAB16F10Caspase-9Endoplasmic reticulum stressJAK-2STAT-5
Abstract
Caffeic acid (CA) is a phenolic compound found naturally in plants and foods. CA and its natural derivatives are reported to have anti-cancer effects on many cancers, including melanoma. (E)-N-(4-Butylphenyl)-3-(3,4-dihydroxyphenyl)acrylamide (4-BPCA) is an amide derivative of CA. Thus far, the anti-cancer effect and mechanism of 4-BPCA in melanoma cells remain unknown. Here we investigated whether 4-BPCA inhibits the growth of B16F10 cells, a mouse melanoma cell line. Of note, treatment of 4-BPCA at 5 µM for 24 or 48 h significantly reduced the growth (survival) of B16F10 cells. On mechanistic levels, treatment with 4-BPCA for 24 h led to the activation of caspase-9/3, but not caspase-8, in B16F10 cells. 4-BPCA treatment for 2 or 4 h also decreased the expression levels of myeloid B-cell lymphoma 1 (Mcl-1) in B16F10 cells. However, 4-BPCA treatment for the times tested did not influence the expression levels of X-linked inhibitor of apoptosis protein (XIAP) in B16F10 cells. Of interest, treatment of 4-BPCA for 2 or 4 h greatly reduced the phosphorylation levels of JAK-2 and STAT-5 without altering their total protein expression levels. 4-BPCA also had abilities to increase the expression and phosphorylation levels of glucose-regulated protein-78 (GRP-78) and eukaryotic translation initiation factor-2α (eIF-2α) in B16F10 cells. In summary, these results demonstrate firstly that 4-BPCA has a strong growth-inhibitory effect on B16F10 melanoma cells, mediated via activation of the intrinsic caspase pathway, inhibition of JAK-2 and STAT-5, and triggering endoplasmic reticulum (ER) stress.
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