Sodium propionate exerts anticancer effect in mice bearing breast cancer cell xenograft by regulating JAK2/STAT3/ROS/p38 MAPK signaling  

作　　者：Hyun-Soo Park Joo-Hui Han Jeong Won Park Do-Hyung Lee Keun-Woo Jang Miji Lee Kyung-Sun Heo Chang-Seon Myung 

机构地区：[1]Department of Pharmacology,Chungnam National University College of Pharmacy,Daejeon 34134,Republic of Korea [2]Department of Lifetech.Institute,iNtRON Biotechnology,Seongnam-si 13202,Republic of Korea

出　　处：《Acta Pharmacologica Sinica》2021年第8期1311-1323,共13页中国药理学报（英文版）

基　　金：supported by the National Research Foundation of Korea(KRF);funded by the Ministry of Science and ICT(grant no.NRF-2018R1A2A2A05023578).

摘　　要：Propionate is a short-chain fatty acid(SCFA)mainly produced from carbohydrates by gut microbiota.Sodium propionate(SP)has shown to suppress the invasion in G protein-coupled receptor 41(GPR41)and GPR43-overexpressing breast cancer cells.In this study we investigated the effects of SP on the proliferation,apoptosis,autophagy,and antioxidant production of breast cancer cells.We showed that SP(5−20 mM)dose-dependently inhibited proliferation and induced apoptosis in breast cancer cell lines JIMT-1(ER-negative and HER2-expressing)and MCF7(ER-positive type),and this effect was not affected by PTX,thus not mediated by the GPR41 or GPR43 SCFA receptors.Meanwhile,we demonstrated that SP treatment increased autophagic and antioxidant activity in JIMT-1 and MCF7 breast cancer cells,which might be a compensatory mechanism to overcome SP-induced apoptosis,but were not sufficient to overcome SP-mediated suppression of proliferation and induction of apoptosis.We revealed that the anticancer effect of SP was mediated by inhibiting JAK2/STAT3 signaling which led to cell-cycle arrest at G_(0)/G_(1) phase,and increasing levels of ROS and phosphorylation of p38 MAPK which induced apoptosis.In nude mice bearing JIMT-1 and MCF7 cells xenograft,administration of SP(20 mg/mL in drinking water)significantly suppressed tumor growth by regulating STAT3 and p38 in tumor tissues.These results suggest that SP suppresses proliferation and induces apoptosis in breast cancer cells by inhibiting STAT3,increasing the ROS level and activating p38.Therefore,SP is a candidate therapeutic agent for breast cancer.

关 键 词：sodium propionate breast cancer JAK2 STAT3 ROS p38 MAPK 

分 类 号：R965[医药卫生—药理学]