title: Minoxidil is a potential neuroprotective drug for paclitaxel-induced peripheral neuropathy.
abstract: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment. No medication has been shown to be effective in the treatment of CIPN. This study aims to integrate the image-based high-content screening, mouse behavior models and mechanistic cell-based assays to discover potential neuroprotective drugs. Among screened compounds, minoxidil showed the most potent neuroprotective effect against paclitaxel, with regard to neurite outgrowth of dorsal root ganglia (DRG). Minoxidil protected mice from thermal insensitivity and alleviated mechanical allodynia in paclitaxel-treated mice. The ultrastructure and quantified G-ratio of myelin integrity of sciatic nerve tissues supported the observations in mouse behavioral tests. The mechanistic study on DRG neurons suggested that minoxidil suppressed neuroinflammation and remodeled the dysregulation of intracellular calcium homeostasis provoked by paclitaxel. Importantly, minoxidil showed a synergistic anti-tumor effect with paclitaxel both in tumor xenograft models of cervical and breast cancer. Interestingly, the quantitative assays on hair length and hair growth both exhibited that minoxidil significantly improved the hair quality after chemotherapy. Since minoxidil is a drug approved by the Food and Drug Administration (FDA), the safety and biocompatibility are well documented. The immediate next step is to launch an early-stage clinical trial intending to prevent CIPN by minoxidil.
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng Kung University, Taiwan.|Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Taiwan.
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng Kung University, Taiwan.
authors.forename: Li-Hsien
authors.initials: LH
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, College of Medicine, National Cheng Kung University, Taiwan.
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Yeh
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, National Cheng Kung University, Taiwan.
authors.forename: Pei-Ying
authors.initials: PY
authors.lastname: Wu
authors.affiliation: Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yih-Fung
authors.initials: YF
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng Kung University, Taiwan.
authors.forename: Lian-Yun
authors.initials: LY
authors.lastname: Chang
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
authors.forename: Jang-Yang
authors.initials: JY
authors.lastname: Chang
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng Kung University, Taiwan.|Department of Obstetrics and Gynecology, College of Medicine, National Cheng Kung University, Taiwan.|Advanced Optoelectronic Technology Center, National Cheng Kung University, Taiwan.
authors.forename: Meng-Ru
authors.initials: MR
authors.lastname: Shen
mesh_terms: D000505:Alopecia / Q000517:prevention & control; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects* / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008914:Minoxidil / Q000494:pharmacology / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017239:Paclitaxel / Q000009:adverse effects* / Q000627:therapeutic use; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D012584:Sciatic Nerve / Q000473:pathology / Q000648:ultrastructure
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D018696:Neuroprotective Agents; D008914:Minoxidil; D017239:Paclitaxel; D002118:Calcium