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| 題名: | (+)-Bornyl p-Coumarate Extracted from Stem of Piper betle Induced Apoptosis and Autophagy in Melanoma Cells |
| 作者: | Wu, Yu-Jen
Su, Tzu-Rong
Chang, Chi-I
Chen, Chiy-Rong
Hung, Kuo-Feng
Liu, Cheng |
| 貢獻者: | 健康暨護理學院 |
| 關鍵詞: | melanoma
(+)-bornyl p-coumarate
apoptosis
autophagy |
| 日期: | 2020 |
| 上傳時間: | 2020-09-24T06:05:13Z (UTC)
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| 摘要: | (+)-Bornyl p-coumarate is an active substance that is abundant in the Piper betle stem
and has been shown to possess bioactivity against bacteria and a strong antioxidative e ect.
In the current study, we examined the actions of (+)-bornyl p-coumarate against A2058 and
A375 melanoma cells. The inhibition e ects of (+)-bornyl p-coumarate on these cell lines were
assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and the
underlying mechanisms were identified by immunostaining, flow cytometry and western blotting
of proteins associated with apoptosis and autophagy. Our results demonstrated that (+)-bornyl
p-coumarate inhibited melanoma cell proliferation and caused loss of mitochondrial membrane
potential, demonstrating treatment induced apoptosis. In addition, western blotting revealed that
the process is mediated by caspase-dependent pathways, release of cytochrome C, activation of
pro-apoptotic proteins (Bax, Bad and caspase-3/-9) and suppression of anti-apoptotic proteins
(Bcl-2, Bcl-xl and Mcl-1). Also, the upregulated expressions of p-PERK, p-eIF2 , ATF4 and
CCAAT/enhancer-binding protein (C/EBP)-homologous protein (CHOP) after treatment indicated that
(+)-bornyl p-coumarate caused apoptosis via endoplasmic reticulum (ER) stress. Moreover, increased
expressions of beclin-1, Atg3, Atg5, p62, LC3-I and LC3-II proteins and suppression by autophagic
inhibitor 3-methyladenine (3-MA), indicated that (+)-bornyl p-coumarate triggered autophagy in the
melanoma cells. In conclusion, our findings demonstrated that (+)-bornyl p-coumarate suppressed
human melanoma cell growth and should be further investigated with regards to its potential use as
a chemotherapy drug for the treatment of human melanoma. |
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