Comparative assessment of therapeutic safety of norcantharidin, N-farnesyloxy-norcantharimide, and N-farnesyl-norcantharimide against Jurkat T cells relative to human normal lymphoblast

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.

The effects of mouthwashes in human gingiva epithelial progenitor (HGEPp) cells

“…8b). The most ideal substances are the ones where IC50 and maximal non-toxic values are the closest to each other (see adjusted Safety Index = SI) [50]. In our case, the substance meeting the above-mentioned conditions is ClO 2 (SI = 34).…”

“…However, numerous literature data suggest that these compounds (e.g., allantoin, ethyl alcohol (27%), NaF) may have a significant cell viability influencing effect on human cells (e.g., epithelial cells). The safe applicability of materials introduced into the human body is well characterized by the Safety Index (SI), calculated from the non-toxic values of IC50 and maximal non-toxic concentration [50]. Based on the SI and morphometric data, hyper pure ClO 2 proved to be the most favorable among the tested materials.…”

The Medicinal Halophyte Frankenia laevis L. (Sea Heath) Has In Vitro Antioxidant Activity, α-Glucosidase Inhibition, and Cytotoxicity towards Hepatocarcinoma Cells

“…A significant reduction in HepG2 cell viability was observed after the application of the dichloromethane extract of F. laevis with an EC 50 value of 52.1 µg/mL. Conversely, this extract did not show significant cytotoxicity towards the non-tumoral S17 cell line up to the maximum concentration tested (100 µg/mL); as such, it exhibited a selectivity index (SI) of at least 1.9 ( Table 4 ), which means that the sample is less toxic for normal cells than tumoral ones, and that it is safer for therapeutic uses [ 45 ]. The methanol extract also did not show significant cytotoxicity up to 100 µg/mL on both HepG2 and S17 cells ( Table 4 ).…”

Norbornene and Related Structures as Scaffolds in the Search for New Cancer Treatments

“…These derivatives exhibited the highest cytotoxicity, and antiproliferative and apoptotic effects against HepG2 human hepatoma cell lines without cytotoxic effects on murine embryonic liver BNL CL.2 cells [108]. In addition, they proved to be safer anticancer drugs than norcantharidin [109]. Another study based on norcantharidin derivatives was developed by Cheng et al [110].…”