Differential Cytotoxic Effects of Jaspine B in Various Cancer Cells

Abstract

Jaspine B is an anhydrophytosphingosine that is isolated from a marine sponge. Because of its structural similarity to sphingosine, it shows anti-cancer effects in human carcinomas. Therefore, this study aims to investigate its anti-proliferative effect on various cancer cells and to correlate its association with the intracellular accumulation of Jaspine B in relevant cancer cells. The anti-proliferative effect of Jaspine B in various cancer cells was determined by a cell viability test, and the intracellular concentration of Jaspine B in relevant cancer cells was determined using mass spectrometry coupled with liquid chromatography. The correlation coefficient and p value between the cytotoxicity and the cell accumulation of Jaspine B were determined using SPSS 16.1. The cytotoxicity of Jaspine B varied depending on the type of cancer cell when compared the EC50 values of Jaspine B. Breast and melanoma cancer cells were susceptible to Jaspine B, whereas renal carcinoma cells were resistant. The intracellular concentrations of Jaspine B had a reciprocal correlation with the EC50 values in the same cells (r = 0.838). The results suggested that the anti-proliferative effect of Jaspine B was associated with the cellular accumulation of this compound. However, Jaspine B was not a substrate for P-glycoprotein and breast cancer resistance protein, as major efflux pumps caused multidrug resistance. The maintenance of a high intracellular concentration is crucial for the cytotoxic effect of Jaspine B; however, efflux pumps may not be a controlling factor for Jaspine B-related resistance in cancer cells.

Formulation, Characterization, and In Vitro/In Vivo Efficacy Studies of a Novel Liposomal Drug Delivery System of Amphiphilic Jaspine B for Treatment of Synovial Sarcoma

“…Yamato- SS cell line study results indicate that jaspine B formulation in a liposome significantly increased in vitro anticancer potency, with a lower IC 50 than jaspine B ( Figure 6 and Table 2 ). Jaspine B’s efficacy against tumors originating from various tissues has been reported, where its effectiveness was dependent upon steady-state cellular accumulation [ 12 ]. Our observation may also be attributed to improved jaspine B stability and liposomal lipid bilayer impact on enhanced cell permeation and accumulation.…”

Pharmacokinetics of Jaspine B and Enhancement of Intestinal Absorption of Jaspine B in the Presence of Bile Acid in Rats

“…It shows meaningful inhibitory activity against sphingosine kinases (SphK1 and SphK2), which is an important mechanism of action for its anti-proliferative effect [ 28 ]. Jaspine B shows differential efficacy against a variety of tumor types of different tissue origins, and the cellular accumulation of Jaspine B at steady-state is a crucial determining factor of efficacy [ 19 ]. Moreover, the intravenous injection of Jaspine B (200 mg/mouse, equivalent to 6.7 mg/kg) on 4th, 8th, and 12th day dramatically decreased metastatic melanoma cell growth in the lungs of Jaspine B-injected mice on day 14 [ 18 ].…”

“…The T/P ratios in these organs were 6.2, 11.1, 14.4, and 18.5, respectively, and remained elevated 2–4-fold 12 h after a single IV administration of Jaspine B ( Figure 7 ). Since we previously reported that the steady-state drug concentration was important for the anti-cancer efficacy of this compound [ 19 , 35 , 36 ], the tissue distribution of Jaspine B is very important to predict the therapeutic efficacy of this compound. Moreover, this compound showed differential cytotoxicity depending on the cancer cell type, thus the highly tissue distributed features of this compound should be carefully considered in terms of drug response and toxicity.…”

“…The results showed that Jaspine B was the most effective against breast cancer cells (MCF-7, IC 50 = 2.31 μM) and showed differential cytotoxicity towards human breast adenocarcinoma (MDA-MB-231, IC 50 > 100 μM), renal carcinoma (786-O, IC 50 = 29.4 μM), melanoma (MDA-MB-435, IC 50 = 2.60 μM), ovarian (SK-OV3, IC 50 = 4.78 μM), and hepatoma (HepG2, IC 50 = 5.69 μM) cells. The steady-state cellular concentration of Jaspine B was associated with the cytotoxic effect [ 19 ].…”