Picropodophyllotoxin, an Epimer of Podophyllotoxin, Causes Apoptosis of Human Esophageal Squamous Cell Carcinoma Cells Through ROS-Mediated JNK/P38 MAPK Pathways

被引：21

作者：

Kwak, Ah-Won ^{[1
]}

Yoon, Goo ^{[1
]}

Lee, Mee-Hyun ^{[2
]}

Cho, Seung-Sik ^{[1
]}

Shim, Jung-Hyun ^{[1
]}

Chae, Jung-Il ^{[3
,4
]}

机构：

[1] Mokpo Natl Univ, Coll Pharm, Dept Pharm, Jeonnam 58554, South Korea

[2] Dongshin Univ, Coll Korean Med, Naju 58245, Jeollanam, South Korea

[3] Jeonbuk Natl Univ, Dept Dent Pharmacol, Sch Dent, Jeonju 54896, South Korea

[4] Jeonbuk Natl Univ, Inst Oral Biosci, BK21 Plus, Jeonju 54896, South Korea

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2020年 / 21卷 / 13期

基金：

新加坡国家研究基金会;

关键词：

picropodophyllotoxin; esophageal squamous cancer; apoptosis; p38; JNK; CANCER CELLS; GROWTH; DEATH; INDUCTION; STRESS; ARREST;

D O I：

10.3390/ijms21134640

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Esophageal squamous cell carcinoma (ESCC), a major histologic type of esophageal cancer, is one of the frequent causes of cancer-related death worldwide. Picropodophyllotoxin (PPT) is the main component ofPodophyllum hexandrumroot with antitumor activity via apoptosis-mediated mechanisms in several cancer cells. However, the underlying mechanism of the PPT effects in apoptosis induction in cancer remains ambiguous. Hence, in this study, we evaluate the anti-cancer effects of PPT in apoptotic signaling pathway-related mechanisms in ESCC cells. First, to verify the effect of PPT on ESCC cell viability, we employed an MTT assay. PPT inhibited the viability of ESCC cells in time- and dose-dependent manners. PPT induced G2/M phase cell cycle arrest and annexin V-stained cell apoptosis through the activation of the c-Jun N-terminal kinase (JNK)/p38 pathways. Furthermore, the treatment of KYSE 30 and KYSE 450 ESCC cells with PPT induced apoptosis involving the regulation of endoplasmic reticulum stress- and apoptosis-related proteins by reactive oxygen species (ROS) generation, the loss of mitochondrial membrane potential, and multi-caspase activation. In conclusion, our results indicate that the apoptotic effect of PPT on ESCC cells has the potential to become a new anti-cancer drug by increasing ROS levels and inducing the JNK/p38 signaling pathways.

引用

页码：1 / 13

页数：13

共 42 条

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