title: Enhancement of cisplatin-induced colon cancer cells apoptosis by shikonin, a natural inducer of ROS in vitro and in vivo.
abstract: Cisplatin-based therapy is one of the most important chemotherapy treatments for cancers. However, its efficacy is greatly limited by drug resistance and undesirable side effects. Therefore, it is of great importance to develop effective chemosensitization agents to cisplatin. In the present study, we demonstrated the strategy to use shikonin, a natural product from the root of Lithospermum erythrorhizon, as a synergistic agent of cisplatin and elucidated their action mechanisms. The combination of shikonin and cisplatin exhibited synergistic anticancer efficacy and achieved greater selectivity between cancer cells and normal cells. By inducing intracellular oxidative stress, shikonin potentiated cisplatin-induced DNA damage, followed by increased activation of mitochondrial pathway. In addition, inhibition of ROS reversed the apoptosis induced by shikonin and cisplatin, and recovered the depletion of mitochondrial membrane potential, which revealed the vital role of ROS in the synergism. Moreover, HCT116 xenograft tumor growth in nude mice was more effectively inhibited by combined treatment with shikonin and cisplatin. Our findings suggest that the strategy to apply shikonin as a synergistic agent to cisplatin could be a highly efficient way to achieve anticancer synergism by inducing intracellular oxidative stress. Shikonin may be a promising candidate as a chemosensitizer to cisplatin-based therapy for cancer treatments.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China. Electronic address: Hgd810701@163.com.
authors.forename: Guodong
authors.initials: G
authors.lastname: He
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: He
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Riyong
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Pi
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Tianqi
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Liuming
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China. Electronic address: 1157817791@qq.com.
authors.forename: Yubo
authors.initials: Y
authors.lastname: Xie
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage; D005260:Female; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009285:Naphthoquinones / Q000008:administration & dosage*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D004365:Drugs, Chinese Herbal; D009285:Naphthoquinones; D017382:Reactive Oxygen Species; C016101:shikonin; D002945:Cisplatin
keywords: Cisplatin; Colon cancer; Mitochondrial dysfunction; ROS; Shikonin