Isoalantolactone Enhances the Antitumor Activity of Doxorubicin by Inducing Reactive Oxygen Species and DNA Damage

Frontiers in Oncology

Oncology

Libo Jin¹  Shaotang Li²  Xiance Jin²  Huanle Pan²  Congying Xie³  Hehuan Sui³  Chenyu Qiu³  Peisen Zheng³  Tingting Zhang³  Rongrong Shao⁴  Fengjiao Wu⁴  Peng Zou⁵  Ri Cui⁵ 

[1] Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou, China;The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, China;The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, China;Cancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China;The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, China;Cancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China;Wenzhou University-Wenzhou Medical University Collaborative Innovation Center of Biomedical, Wenzhou, China;The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, China;Cancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China;Wenzhou University-Wenzhou Medical University Collaborative Innovation Center of Biomedical, Wenzhou, China;Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou, China;

关键词: colon cancer;    ROS;    isoalantolactone;    JNK;    doxorubicin;    DNA damage;   

DOI  :  10.3389/fonc.2022.813854

 received in 2021-11-12, accepted in 2022-01-05,  发布年份 2022

来源: Frontiers

【 摘 要 】

Colon cancer is one of the most common cancer in the world. Doxorubicin (DOX) is a classical anti-tumor drug which widely used in treatment of cancers, however, high toxicity limited its further clinical application. Thus, it is urgent to find new drugs with low toxicity and high efficiency to treat colon cancer. Isoalantolactone (IATL), an isomeric sesquiterpene lactone isolated from the plant of inula helenium, has been reported to have anti-cancer activity against a variety of cancer cells. However, the function of IATL in colon cancer remains unclear. Here, we demonstrated that IATL inhibited colon cancer cell growth by increasing cellular reactive oxygen species (ROS) production. Further study showed that ROS accumulation contributed to DNA damage and JNK signaling pathway activation. In addition, we found that IATL markedly enhanced DOX-induced cell cytotoxicity in colon cancer cells. IATL in combination with DOX significantly increased the ROS production, induced DNA damage and activated JNK signaling pathway. Taken together, our data suggested that combined treatment with IATL and DOX may serve as a potential therapeutics for colon cancer.

【 授权许可】

Unknown   
Copyright © 2022 Wu, Shao, Zheng, Zhang, Qiu, Sui, Li, Jin, Pan, Jin, Zou, Cui and Xie