title: Comparative assessment of therapeutic safety of norcantharidin, N-farnesyloxy-norcantharimide, and N-farnesyl-norcantharimide against Jurkat T cells relative to human normal lymphoblast: A quantitative pilot study.
abstract: The therapeutic safety of an anticancer drug is one of the most important concerns of the physician treating the cancer patient. Half maximal inhibitory concentration (IC50) and hillslope are usually used to represent the strength and sensitivity of an anticancer drug on cancer cells. The therapeutic safety of the anticancer drug can be assessed by comparing the IC50 and hillslope of anticancer drugs on cancer cells relative to normal cells. Since there are situations where "more anticancer activity" implies "more toxicity," the safety of an anticancer drug in these situations is hard to evaluate by using IC50 and hillslope alone. In a previous study, the "net effect" index was devised to represent the net therapeutic effects of one anticancer drug relative to the other. However, the therapeutic safety of one specific anticancer drug alone was not defined in the "net effect" index. This study introduced the "safety index (SI)" to quantify the degree of safety of an anticancer drug by using 4-parameter logistic model on cancer cells relative to normal cells. The therapeutic safety of norcantharidin (NCTD), N-farnesyloxy-norcantharimide (NOC15), and N-farnesyl-norcantharimide (NC15) in the treatment of Jurkat T cells relative to human normal lymphoblast was compared using the newly defined SI. We found that the SI of NOC15 and NC15 was significantly higher than that of NCTD, suggesting that both NOC15 and NC15 can damage more cancer cells and less normal cells than NCTD. We conclude that both NOC15 and NC15 are safer anticancer drugs than NCTD in the treatment of Jurkat T cells relative to human normal lymphoblast. The SI can be further applied to the screening, developments, and applications of anticancer drugs in the future.
authors: Laboratory of Biophysics, Department of Medical Research, Taipei Veterans General Hospital, Taipei Department of Microbiology, Immunology and Biopharmaceutics, College of Life Sciences Department of Molecular Biology and Biochemistry, National Chiayi University, Chiayi Department of Radiation Oncology, Mackay Memorial Hospital, Taipei Chest Medicine and Physiological Signals Research Center, Changhua Christian Hospital, Changhua, Taiwan.
authors: Ming-Che
authors: MC
authors: Chang
authors: Jin-Yi
authors: JY
authors: Wu
authors: Hui-Fen
authors: HF
authors: Liao
authors: Yu-Jen
authors: YJ
authors: Chen
authors: Cheng-Deng
authors: CD
authors: Kuo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002193:Cantharidin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019169:Jurkat Cells; D016015:Logistic Models; D008214:Lymphocytes / Q000187:drug effects*; D010865:Pilot Projects
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; C000602634:N-farnesyl-norcantharimide; C000602633:N-farnesyloxy-norcantharimide; C069741:norcantharidin; D002193:Cantharidin