{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T13:29:41Z","timestamp":1746538181504,"version":"3.37.3"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T00:00:00Z","timestamp":1601510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100007831","name":"University of Tabriz","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007831","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Uncontrolled cell proliferation was caused by multiple deficient pathways that inhibition of one pathway may result to activate an alternative pathway. Therefore, combination of drugs which targeted multiple pathways could be beneficial to overcome drug resistance. Ciprofloxacin (CPF) cytotoxicity was widely investigated on cancer cell lines, and results revealed hepatoma-derived Hep G2 cells are relatively resistant. So, this study aimed to increase CPF cytotoxicity by rational design of a supplement which targeted Ca2+ homoeostasis as major hub in unchecked proliferation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Cells were treated by CPF and\/or pilocarpine (PILO), and cell cycle distribution, caspases activity and regulatory proteins were evaluated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>MTT and flow cytometry analysis confirmed administration of CPF + PILO causes more cytotoxicity. CPF-exposed cells accumulated in S phase due to DNA damages while PILO + CPF imposed G0 stage arrest through cyclin D1 and P-Akt downregulation. Caspase 8 was activated in cells treated by CPF but accompaniment of PILO with CPF led to activation of caspase 9, 8 and 3 and ROS overproduction.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Ciprofloxacin imposed mitochondrial-independent apoptosis while PILO + CPF caused mitochondrial-dependent and independent apoptosis simultaneously. Consequently, coadministration of PILO and CPF causes intense cytotoxic effects through targeting the mitochondria, DNA gyrase enzyme and other unknown mechanisms.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1111\/jphp.13318","type":"journal-article","created":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T04:49:57Z","timestamp":1592801397000},"page":"1383-1393","source":"Crossref","is-referenced-by-count":2,"title":["Cumulative effects of ciprofloxacin and pilocarpine on cytotoxicity and G0 phase arrest in hepatoma-derived Hep G2 cell line"],"prefix":"10.1093","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1829-4388","authenticated-orcid":false,"given":"Leila","family":"Sadeghi","sequence":"first","affiliation":[{"name":"Department of Biology, Faculty of Natural Sciences, University of Tabriz , Tabriz,","place":["Iran"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Somaiyeh","family":"Maleki","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Natural Sciences, University of Tabriz , Tabriz,","place":["Iran"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gholamreza","family":"Dehghan","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Natural Sciences, University of Tabriz , Tabriz,","place":["Iran"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,10,1]]},"reference":[{"key":"2024103012350770900_jphp13318-cit-0001","first-page":"233","article-title":"Ciprofloxacin inhibits proliferation and promotes generation of aneuploidy in Jurkat cells","volume":"61","author":"Koziel","year":"2010","journal-title":"J Physiol 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