Original articles
Huanmin Niu, Lilin Qian, Bin Sun, Wenjian Liu, Fang Wang, Qian Wang, Xiaotian Ji, Yanhai Luo, Effat Un Nesa, Hongxiang Lou, Huiqing Yuan. Inactivation of TFEB and NF-κB by marchantin M alleviates the chemotherapy-driven protumorigenic senescent secretion[J]. Acta Pharmaceutica Sinica B, 2019, 9(5): 923-936

Inactivation of TFEB and NF-κB by marchantin M alleviates the chemotherapy-driven protumorigenic senescent secretion
Huanmin Niua, Lilin Qiana, Bin Sunb, Wenjian Liua, Fang Wanga, Qian Wanga, Xiaotian Jia, Yanhai Luoa, Effat Un Nesac, Hongxiang Loub, Huiqing Yuana
a Institute of Medical Sciences/Department of Biochemistry and Molecular Biology, the Second Hospital of Shandong University, Jinan 250033, China;
b Key Laboratory of Natural Products & Chemical Biology, Ministry of Education, Department of Natural Products Chemistry, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China;
c Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012, China
Abstract:
It is critical to regulate the senescence-associated secretory phenotype (SASP) due to its effect on promoting malignant phenotypes and limiting the efficiency of cancer therapy. In this study, we demonstrated that marchantin M (Mar-M, a naturally occurring bisbibenzyl) suppressed proinflammatory SASP components which were elevated in chemotherapy-resistant cells. Mar-M treatment attenuated the pro-tumorigenic effects of SASP and enhanced survival in drug-resistant mouse models. No toxicity was detected on normal fibroblast cells or in animals following this treatment. Inactivation of transcription factor EB (TFEB) and nuclear factor-κB (NF-κB) by Mar-M significantly accounted for its suppression on the components of SASP. Furthermore, inhibition of SASP by Mar-M contributed to a synergistic effect during co-treatment with doxorubicin to lower toxicity and enhance antitumor efficacy. Thus, chemotherapy-driven pro-inflammatory activity, seen to contribute to drug-resistance, is an important target for Mar-M. By decreasing SASP, Mar-M may be a potential approach to overcome tumor malignancy.
Key words:    SASP    Marchantin M    TFEB    NF-κB    Drug resistance   
Received: 2019-07-01     Revised: 2019-08-04
DOI: 10.1016/j.apsb.2019.08.007
Funds: This work was supported by the National Natural Science Foundation of China (81473238, 81872896, and 81874293), and the Shandong Key Innovative Research Program (2018CXGC1216, China).
Corresponding author: Huiqing Yuan     Email:lyuanhq@sdu.edu.cn
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Authors
Huanmin Niu
Lilin Qian
Bin Sun
Wenjian Liu
Fang Wang
Qian Wang
Xiaotian Ji
Yanhai Luo
Effat Un Nesa
Hongxiang Lou
Huiqing Yuan

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