Anti-cancer effect of marchantin C via inducing lung cancer cellular senescence associated with less secretory phenotype.

Autor: Zhang XL; Institute of Medical Sciences, The Second Hospital of Shandong University, Jinan, China; Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, China., Ji XT; Institute of Medical Sciences, The Second Hospital of Shandong University, Jinan, China; Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, China., Sun B; Key Laboratory of Natural Products & Chemical Biology, Ministry of Education, Department of Natural Products Chemistry, National Glycoengineering Research Center, School of Pharmaceutical Sciences, Shandong University, Jinan, China., Qian LL; Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, China., Hu XL; Department of thoracic surgery, Qilu Hospital of Shandong University, Jinan, China., Lou HX; Key Laboratory of Natural Products & Chemical Biology, Ministry of Education, Department of Natural Products Chemistry, National Glycoengineering Research Center, School of Pharmaceutical Sciences, Shandong University, Jinan, China., Yuan HQ; Institute of Medical Sciences, The Second Hospital of Shandong University, Jinan, China; Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, China. Electronic address: lyuanhq@sdu.edu.cn.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. General subjects [Biochim Biophys Acta Gen Subj] 2019 Oct; Vol. 1863 (10), pp. 1443-1457. Date of Electronic Publication: 2019 May 16.
DOI: 10.1016/j.bbagen.2019.05.006
Abstrakt: Background: Lung cancer is the leading cause of global cancer deaths. Current chemotherapeutic agents for lung cancer treatment are generally accompanied with severe side effects. Here, we report that marchantin C (Mar-C), a potential natural compound with little chemotherapeutic toxicity, exerts a well anti-tumor effect against lung cancer via inducing cellular senescence.
Methods: The antitumor activity of Mar-C was evaluated by MTT and colony formation in vitro cytotoxicity assays, and xenograft and homograft in vivo model. Antitumor mechanisms of Mar-C were investigated through SA-β-gal staining, Q-PCR, immunoblotting, immunofluorescence, protein array and siRNA knocking-down analysis.
Results: Mar-C selectively induces senescence of lung cancer cells with limited cytotoxicity on normal or non-neoplastic cells. Mar-C-induced senescence was associated with the elevation of ROS and activation of DNA-damage, and largely dependent of prolonged p21 CIP1 accumulation. The senescence-associated secretory phenotype (SASP) induced by Mar-C was distinct from doxorubicin-induced. Furthermore, Mar-C exhibited an inhibitory activity on tumor growth with little toxicity in animal studies, and significantly prolonged the survival time of tumor-bearing mice than that of doxorubicin or vehicle treatments.
Conclusion: Mar-C selectively inhibited tumor growth via the induction of cancer cell senescence and had little chemotherapeutic toxicity, suggesting the potential of Mar-C as a promising anticancer agent.
General Significance: This study provided evidence to identify a novelty of Mar-C that exerted antitumor activity on lung cancer through induction of senescence with limited toxicity.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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