Sinodielide A (SA) is a naturally occurring guaianolide, which is isolated from 
the root of Sinodielsia yunnanensis. This root, commonly found in Yunnan 
province, is used in traditional Chinese medicine as an antipyretic, analgesic 
and diaphoretic agent. A number of studies have reported that agents isolated 
from a species of Umbelliferae (Apiaceae) have antitumor activities. We 
previously reported, using combined treatments with this medicinal herb and 
hyperthermia at various temperatures, an enhanced cytotoxicity in the human 
prostate cancer androgen‑independent cell lines, PC3 and DU145, and analyzed the 
related mechanisms. In the present study, we investigated the effects of 
treatment with SA prior to hyperthermia on the thermosensitivity of DU145 cells, 
and the mechanisms related to the induction of apoptosis and G(2)/M cell cycle 
arrest via the activation of extracellular-regulated kinase (ERK)1/2, c-Jun 
N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) signaling 
pathways, as well as the phosphoinositide 3-kinase (PI3K)/Akt signaling 
pathways. Cells were exposed to hyperthermia alone (40-44˚C) or hyperthermia in 
combination with SA. Lethal damage to cells treated with mild hyperthermia (40 
or 42˚C) for up to 6 h was slight; however, hyperthermia in combination with SA 
synergistically enhanced thermosensivity. Lethal damage to cells treated with 
acute hyperthermia (43 or 44˚C) was more severe, but these effects were also 
enhanced and were more significant by the combined treatment with SA. The 
kinetics of apoptosis induction and cell cycle distribution were analyzed by 
flow cytometry. In addition, the levels of ERK1/2, JNK and Akt were determined 
by western blot analysis. The incidence of apoptotic cells after treatment with 
SA (20.0 µM) at 37˚C for 4 h, hyperthermia (44˚C) alone for 30 min, and the 
combination in sequence were examined. The sub-G1 division (%) in the diagram 
obtained by flow cytometry was applied to that assay. The percentage of 
apoptotic cells (10.53±5.02%) was higher at 48 h as compared to 0, 12 and 24 h 
after treatment. The distribution of DU145 cells in the G2/M cell cycle phase 
was markedly increased after 24 h of heating at 44˚C and after the combined 
treatment with heating and SA. The phosphorylation of ERK1/2 was reduced 
following treatment with heating and SA, while the levels of phosphorylated JNK 
(p-JNK) were markedly increased immediately after heating at 44˚C and when 
heating was combined with SA. By contrast, the levels of phosphorylated Akt 
(p-Akt) were immediately increased only after heating at 44˚C. Thus, we 
concluded that SA exerts its thermosensitizing effects on DU145 cells by 
inhibiting the activation of the MAPK/ERK1/2 and PI3K/Akt signaling pathways.