title: Doxycycline inhibits proliferation and induces apoptosis of both human papillomavirus positive and negative cervical cancer cell lines.
abstract: The clinical management of cervical cancer remains a challenge and the development of new treatment strategies merits attention. However, the discovery and development of novel compounds can be a long and labourious process. Drug repositioning may circumvent this process and facilitate the rapid translation of hypothesis-driven science into the clinics. In this work, we show that a FDA-approved antibiotic, doxycycline, effectively targets human papillomavirus (HPV) positive and negative cervical cancer cells in vitro and in vivo. Doxycycline significantly inhibits proliferation of a panel of cervical cancer cell lines. It also induces apoptosis of cervical cancer cells in a time- and dose-dependent manner. In addition, the apoptosis induced by doxycycline is through caspase-dependent pathway. Mechanism studies demonstrate that doxycycline affects oxygen consumption rate, glycolysis, and reduces ATP levels in cervical cancer cells. In HeLa xenograft mouse model, doxycycline significantly inhibits growth of tumour. Our in vitro and in vivo data clearly demonstrate the inhibitory effects of doxycycline on the growth and survival of cervical cancer cells. Our work provides the evidence that doxycycline can be repurposed for the treatment of cervical cancer and targeting energy metabolism may represent a potential therapeutic strategy for cervical cancer.
authors.affiliation: Shandong Provincial Hospital affiliated to Shandong University, 324 Jingwu Rd., Huaiyin Dist., Jinan 250021, Shandong Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Shandong Provincial Hospital affiliated to Shandong University, 324 Jingwu Rd., Huaiyin Dist., Jinan 250021, Shandong Province, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Shandong Provincial Hospital affiliated to Shandong University, 324 Jingwu Rd., Huaiyin Dist., Jinan 250021, Shandong Province, China.|Shandong Provincial Hospital affiliated to Shandong University, 324 Jingwu Rd., Huaiyin Dist., Jinan 250021, Shandong Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Shandong Provincial Hospital affiliated to Shandong University, 324 Jingwu Rd., Huaiyin Dist., Jinan 250021, Shandong Province, China.|Shandong Provincial Hospital affiliated to Shandong University, 324 Jingwu Rd., Huaiyin Dist., Jinan 250021, Shandong Province, China.
authors.forename: Changzhong
authors.initials: C
authors.lastname: Li
mesh_terms: D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004318:Doxycycline / Q000494:pharmacology / Q000627:therapeutic use*; D058492:Drug Repositioning; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D016513:Mice, SCID; D010101:Oxygen Consumption / Q000187:drug effects; D027383:Papillomaviridae / Q000187:drug effects* / Q000302:isolation & purification; D011897:Random Allocation; D047368:Tumor Burden / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D000998:Antiviral Agents; D000255:Adenosine Triphosphate; D004318:Doxycycline
keywords: cancer du col de l’utérus; cervical cancer; doxycycline; drug repositioning; energy metabolism; métabolisme énergétique; réaffectation de médicaments