title: Design, Synthesis, and Biological Evaluation of Novel Selenium (Se-NSAID) Molecules as Anticancer Agents.
abstract: The synthesis and anticancer evaluation of novel selenium-nonsteroidal anti-inflammatory drug (Se-NSAID) hybrid molecules are reported. The Se-aspirin analogue 8 was identified as the most effective agent in reducing the viability of different cancer cell lines, particularly colorectal cancer (CRC) cells, was more selective toward cancer cells than normal cells, and was >10 times more potent than 5-FU, the current therapy for CRC. Compound 8 inhibits CRC growth via the inhibition of the cell cycle in G1 and G2/M phases and reduces the cell cycle markers like cyclin E1 and B1 in a dose dependent manner; the inhibition of the cell cycle may be dependent on the ability of 8 to induce p21 expression. Furthermore, 8 induces apoptosis by activating caspase 3/7 and PARP cleavage, and its longer exposure causes increase in intracellular ROS levels in CRC cells. Taken together, 8 has the potential to be developed further as a chemotherapeutic agent for CRC.
authors.affiliation: Department of Organic and Pharmaceutical Chemistry, University of Navarra , Irunlarrea 1, E-31008 Pamplona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Plano
authors.affiliation: Department of Pharmacology, Penn State Hershey Cancer Institute, CH72, Penn State College of Medicine , 500 University Drive, Hershey, Pennsylvania 17033, United States.
authors.forename: Deepkamal N
authors.initials: DN
authors.lastname: Karelia
authors.affiliation: Department of Pharmacology, Penn State Hershey Cancer Institute, CH72, Penn State College of Medicine , 500 University Drive, Hershey, Pennsylvania 17033, United States.
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Pandey
authors.affiliation: Department of Nutrition, Texas Tech University , Lubbock, Texas 79430, United States.
authors.forename: Julian E
authors.initials: JE
authors.lastname: Spallholz
authors.affiliation: Department of Pharmacology, Penn State Hershey Cancer Institute, CH72, Penn State College of Medicine , 500 University Drive, Hershey, Pennsylvania 17033, United States.
authors.forename: Shantu
authors.initials: S
authors.lastname: Amin
authors.affiliation: Department of Pharmacology, Penn State Hershey Cancer Institute, CH72, Penn State College of Medicine , 500 University Drive, Hershey, Pennsylvania 17033, United States.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Sharma
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D016566:Organoselenium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D016566:Organoselenium Compounds