Anacardic acid sensitizes prostate cancer cells to radiation therapy by regulating H2AX expression

Abstract

Anacardic acid (6-pentadecylsalicylic acid, AA), a natural compound isolated from the traditional medicine Amphipterygiumadstringens, has been reported as potential antitumor agents in various cancers including prostate cancer (PC). However, the effects and mechanism of AA on the radiosensitivity of prostate cancer remains unknown. The results indicated that AA exhibited strong antitumor activity in PC cell lines, either as a single agentor in combination with radiation. AA significantly induced the downregulation of H2AX and p-H2AX expression, increase of cell apoptosis and decreasing of cell invasion, which were reversed by overexpressed H2AX. These results suggest that AA sensitize prostate cancer cells to radiation therapy by repressing H2AX expression.

Keywords: Anacardic acid; H2AX; prostate cancer; radio therapy.

Figure 1

A. AA inhibited the growth of PC3 cells in a dose-dependent manner. *P<0.05 versus control group. B. AA1 radio sensitized PC3 cell lines. PC3 cells were irradiated at a single dose of 0, 2, 4, 6 or 8 Gy in the presence or absence of AA (IC25 concentration for each cell line). Data were showed as mean ± SD of three experiments. P<0.05 for each radiation dose in combination with AA versus each radiation dose alone for both of the two cell lines.

Figure 2

AA induced PC cell death via apoptosis. Apoptosis for all treatments of PC3 cells. Combination of radiation and AA induced significant apoptosis in PC cell line. Bargraphs represent the total apoptosis of all conditions. The total amount of apoptosis was the results of early apoptosis plus late apoptosis. Data were shown as mean ± SD of three experiments. *P<0.05 versus control or radiation alone; **P<0.05 versus control or other treatment alone.

Figure 3

AA sensitized PC cells to radiation by inhibiting cell invasion. Invasion for all treatments of PC3 cells. Combination of radiation and AA induced significant invasion in PC cell line. Bargraphs represent the total apoptosis of all conditions. Data were shown as mean ± SD of three experiments. *P<0.05 versus control or radiation alone; **P<0.05 versus control or other treatment alone.

Figure 4

H2AX involved AA-induced radio sensitivity in PC cells. (A) The effects of AA and radiation on H2AX expression and γ-H2AX expression. Data were showed as mean ± SD of three experiments. *P<0.05 versus control or radiation alone; **P<0.05 versus control or other treatment alone. (B) H2AX overexpression in PC cells. (C) H2AX involved proliferation and (D), H2AX involved invasion of PC cells. Data were showed as mean ± SD of three experiments. *P<0.05 versus control; **P<0.05 versus AA and radiation treatment group.