Bioactive Materials (Jul 2022)
Curcumenol triggered ferroptosis in lung cancer cells via lncRNA H19/miR-19b-3p/FTH1 axis
- Ruonan Zhang,
- Ting Pan,
- Yu Xiang,
- Mingming Zhang,
- Han Xie,
- Zimao Liang,
- Bi Chen,
- Cong Xu,
- Jing Wang,
- Xingxing Huang,
- Qianru Zhu,
- Ziming Zhao,
- Quan Gao,
- Chengyong Wen,
- Wencheng Liu,
- Weirui Ma,
- Jiao Feng,
- Xueni Sun,
- Ting Duan,
- Elaine Lai-Han Leung,
- Tian Xie,
- Qibiao Wu,
- Xinbing Sui
Affiliations
- Ruonan Zhang
- State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau; School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
- Ting Pan
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
- Yu Xiang
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
- Mingming Zhang
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
- Han Xie
- State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau; School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
- Zimao Liang
- State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau; School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
- Bi Chen
- State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau; School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
- Cong Xu
- State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau
- Jing Wang
- State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau
- Xingxing Huang
- State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau; School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
- Qianru Zhu
- State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau; School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
- Ziming Zhao
- State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau
- Quan Gao
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
- Chengyong Wen
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
- Wencheng Liu
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
- Weirui Ma
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
- Jiao Feng
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
- Xueni Sun
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
- Ting Duan
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
- Elaine Lai-Han Leung
- State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau
- Tian Xie
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China; Corresponding author. School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China.
- Qibiao Wu
- State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau; Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangzhou, 510006, China; Corresponding author. State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau.
- Xinbing Sui
- State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau; School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China; Corresponding author. School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China.
- Journal volume & issue
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Vol. 13
pp. 23 – 36
Abstract
Curcumenol, an effective ingredient of Wenyujin, has been reported that exerted its antitumor potential in a few cancer types. However, the effect and molecular mechanism of curcumenol in lung cancer are largely unknown. Here, we found that curcumenol induced cell death and suppressed cell proliferation in lung cancer cells. Next, we demonstrated that ferroptosis was the predominant method that contributed to curcumenol-induced cell death of lung cancer in vitro and vivo for the first time. Subsequently, using RNA sequencing, we found that the long non-coding RNA H19 (lncRNA H19) was significantly downregulated in lung cancer cells treated with curcumenol, when compared to untreated controls. Overexpression of lncRNA H19 eliminated the anticancer effect of curcumenol, while lncRNA H19 knockdown promoted ferroptosis induced by curcumenol treatment. Mechanistically, we showed that lncRNA H19 functioned as a competing endogenous RNA to bind to miR-19b-3p, thereby enhanced the transcription activity of its endogenous target, ferritin heavy chain 1 (FTH1), a marker of ferroptosis. In conclusion, our data show that the natural product curcumenol exerted its antitumor effects on lung cancer by triggering ferroptosis, and the lncRNA H19/miR-19b-3p/FTH1 axis plays an essential role in curcumenol-induced ferroptotic cell death. Therefore, our findings will hopefully provide a valuable drug for treating lung cancer patients.
