β, β-Dimethylacrylshikonin Triggers Caspase-Mediated Cell Apoptosis via Heme Oxygenase-1 Upregulation and ERK/p38 Activation in Prostate Cancer.

β, β-Dimethylacrylshikonin (DMAS), a natural naphthoquinone derivative isolated from the root of a biennial herb belonging to the family Boraginaceae, has been demonstrated to exhibit anti-cancer and anti-inflammatory features. Yet, the effects of DMAS on restraining the progression of prostate cancer (PC) remain mostly elusive. Here, we attempted to examine whether DMAS hampers PC progression and subsequently explored the underlying mechanisms. Our results demonstrate that DMAS elicited cytotoxicity to PC cell lines, DU-145 and PC-3 cells, along with promotion of apoptosis and cell cycle arrest. Moreover, fluctuations in the levels of many potential apoptosis markers (upregulation of HO-1 and downregulation of cIAP-1 and XIAP) and activation of caspase pathways were observed in DMAS-treated PC cell lines. Furthermore, DMAS-induced caspase activations in PC cells were affected by silencing of HO-1 and the pretreatment with a selective ERK (U0126) or p38 inhibitor (SB203580), unveiling a functional linkage of HO-1, ERK, and p38 signalling to the responses of DMAS-treated PC cells. In conclusion, our results revealed that DMAS induced activation of caspase cascades to elicit cell apoptosis in PC, through HO-1 upregulation and ERK/p38 activation. These findings provide possible avenues for the use of a naturally occurring compound with therapeutic values in fighting prostate carcinogenesis.