Patchouli alcohol suppresses castration-resistant prostate cancer progression by inhibiting NF-κB signal pathways

Abstract

Background: There is evidence that patchouli alcohol (PA) has cytotoxic effects on human cancer cell lines, including inhibiting cell growth, migration, and invasion. However, the exact molecular mechanism of PA in human castration-resistant prostate cancer (CRPC) cells remains unclear. Methods: DU145 and PC-3 cells were treated with different concentrations of PA for 48 h. Cell counting kit-8 (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) staining were used to detect cell proliferation. Scratch tests and transwell assays were used to detect cell migration and invasion. TdTmediated dUTP nick-end labeling (TUNEL) staining and flow cytometry were performed to examine apoptosis and mitochondrial membrane potential. The expression of the apoptosis-and migration-related proteins and the phosphorylation of the nuclear factor kappa -B (NF-κB) cells were detected by Western blot. A chromatin immunoprecipitation (ChIP) analysis was conducted to examine NF-κB p65 binding to the myeloid cell leukemia-1 (Mcl-1) promoter. A xenograft model of nude mice was established to verify the anticancer effects of PA in vivo. Results: PA inhibited the proliferation, migration, and invasion, and induced the apoptosis of the DU145 and PC-3 cells in a concentration-dependent manner, and was accompanied by mitochondrial membrane potential depolarization, the upregulation of cleaved caspase-3, cleaved poly ADP-ribose polymerase (PARP) and Bcl-2-associated X protein (Bax), and the downregulation of B-cell lymphoma-2 (Bcl-2), Ki67, and Mcl-1. In relation to the mechanism, PA significantly downregulated the phosphorylation of inhibitor of NF-κB α (IκBα) and p65 and the expression of matrix metalloprotein (MMP)-2, MMP-7, MMP-9, and vascular endothelial growth factor (VEGF). PA prevented p65 binding to the Mcl-1 promoter by inactivating NF-κB p65, downregulated the transcription of Mcl-1, and the silencing of p65 increased the sensitivity of the CRPC cells to PA-induced apoptosis. The overexpression of Mcl-1 significantly reversed the PA-induced apoptosis of the CRPC cells. Additionally, consistent with our in-vitro study, PA inhibited tumor growth in the mouse xenograft model. Conclusions:We found that PA inhibits the growth, migration, and invasion of CRPC cells in vitro and in vivo by inducing an apoptosis mechanism and inhibiting NF-κB activity. Our findings may provide therapeutic targets for this malignant tumor.

Patchouli alcohol inhibits GPBAR1-mediated cell proliferation, apoptosis, migration, and invasion in prostate cancer

“…However, very few reports have examined the anti-cancer activity of PA and potential mechanisms of PCa. Our previous research demonstrated that PA inhibited the cell proliferation, migration, and invasion, and induced the apoptosis of PCa cells (18). In the present study, network pharmacology predicted that GPBAR1 was a PA target.…”

“…In this study, we found GPBAR1 inhibited the phosphorylation of IkBα, which promoted p65 phosphorylation release in vivo and in vitro (29). We previously showed that PA induced PCa cell apoptosis by inhibiting NF-κB activity (18). Together, these findings indicate that PA inhibits PCa progression through the GPBAR1/NF-κB pathway.…”

“…The GSEA showed that the expression of GPBAR1 was associated with cell proliferation, migration, and invasion (see Figure 1D-1F). Further, we observed that PA inhibited the expression of GPBAR1 protein in a timeand dose-dependent manner (18) in the PC-3 and DU145 cells (see Figure 1G,1H).…”

“…Previous research has shown that patchouli alcohol (PA) inhibits the cell malignant progression of PCa (18). The gene set enrichment analysis (GSEA) predicted that GPBAR1 affects the proliferation, migration, and invasion of PCa, and the network pharmacology analysis showed that GPBAR1 might be a potential target of PA. We hypothesized that PA could restrain the proliferation, migration, and invasion of PCa by regulating GPBAR1.…”

The effects of patchouli alcohol and combination with cisplatin on proliferation, apoptosis and migration in B16F10 melanoma cells

“…46 The genetics and histological characteristics of murine melanoma are known to be similar to those of human melanoma. 47 PA exhibited growth inhibitory activity not only against mouse melanoma B16F10 cells, but also against human prostate cancer cells (PC3 and DU145), lung cancer cells (A549) and colorectal cancer cells (HCT116 and SW480), [25][26][27] suggesting that it had the potential of anti-cancer in both mouse and human cancers. The findings indicate that PA may be a potential compound for the development of novel drugs or adjuvants that can be used in combination with clinical drugs to improve side effects and drug resistance.…”