JVM-13

Shikonin Exert Antitumor Activity in JVM-13 Cells

Shikonin is a well-known antitumor substance that induces apoptosis, inhibits proliferation of cancer cells, and inhibits angiogenesis. The antitumor activity of shikonins in JVM-13, human B-PLL cells was explored. As shown in Fig. 1, derivatives of shikonin isobutyrylshikonin (IBS) and α-methylbutyrylshikonin (MBS) decreased the viability of JVM-13 cells in a dose-dependent manner. From a concentration of 110 μg/mL, both IBS and MBS reduced the viability of JVM-13 cells to 100% (Fig. 1).

As illustrated in Fig. 2, IBS- and MBS-induced apoptosis and the majority of JVM-13 cells were in or occurred during late apoptosis. Quantitative analysis of Bcl-2, Bax, Mcl-1, and Noxa molecules in JVM-13 cells strongly indicated apoptotic death of JVM-13 cells after treatment with MBS and IBS. Treatment of JVM-13 cells with IBS and MBS at a concentration of 2 µg/mL significantly attenuated the percentage of Mcl-1-expressing cells and significantly enhanced the percentage of cells that expressed the pro-apoptotic molecule Noxa, even at a lower concentration of 1 µg/mL (Fig. 2c). Analysis of Bax and Bcl-2 expression at mRNA levels also showed significant attenuation of Bcl-2 and enhancement of Bax mRNA levels after treatment of JVM-13 cells with IBS and MBS (Fig. 2d). The antiproliferative effects of testing molecules were evaluated by assessment of the Ki67 expression level in treated cells using flow cytometry. The percentage of Ki67-positive JVM-13 cells (Fig. 3) treated with IBS and MBS was significantly lower compared to untreated cells.

Fig. 1 Dose- and time-dependent cytotoxicity of IBS and MBS on the JVM-13 cell line. (Todorovic Z, et al., 2021)

Fig. 2 IBS and MBS induce apoptotic death of JVM-13 cells. (Todorovic Z, et al., 2021)

Fig. 3 IBS and MBS attenuate the expression of Ki67 in JVM-13 cells. (Todorovic Z, et al., 2021)