Ardisianone, a natural benzoquinone, efficiently induces apoptosis in human hormone‐refractory prostate cancers through mitochondrial damage stress and survivin downregulation

Abstract

The data suggest that the ardisianone induces apoptosis in human prostate cancers through mitochondrial damage stress, leading to the inhibition of mTOR/p70S6K pathway, downregulation of Bcl-2 family members, degradation of survivin, and activation of caspase cascades. The data provide evidence supporting that ardisianone is a potential anticancer agent against HRPCs.

Antiproliferative and antimicrobial activities of alkylbenzoquinone derivatives fromArdisia kivuensis

“…In fact, it has been recognized that apoptotic cells have a reduced DNA stainability following the staining with fluorochromes such as PI, therefore the appearance of cells with low DNA stainability, lower than that of G1 cells (sub-G1) in cultures treated with drugs has been considered to be the hallmark of cell death by apoptosis (Darzynkiewicz et al, 1992;Nicoletti et al, 1991). Our findings were similar to the recent observation made from ardisianone, a natural benzoquinone derivative, which was shown to display antiproliferative and apoptotic activities against human hormonerefractory prostate cancer cells (HRPC), PC-3 and DU-145 (Yu et al, 2013). However, hypodiploid DNA peak sometimes may consist of apoptotic cells, necrotic cells, debris blebs of cytotoxic drugs and other debris, resulting either in a strong overestimation of apoptotic cell percentage because isolated apoptotic bodies are counted as apoptotic cells or in an underestimation of the phenomenon if apoptotic cells are gated out as debris (Darzynkiewicz et al, 1992).…”

A Tale of Two Glutaminases: Homologous Enzymes with Distinct Roles in Tumorigenesis

“…Notably, AV-1, better known as ardisianone, is a major product of many species of Ardisia, which have been used for centuries in traditional Chinese medicine. The compound has been shown to lead to mitochondrial failure, apoptosis and downregulation of survivin, an important prosurvival protein in many cancers [140][141][142] and it is possible that it might have a dditional cellular targets besides LGA.…”

Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPs)

“…shRNA mediated knockdown of survivin is an effective strategy to re-sensitize H292 lung cancer cells to cisplatin therapy [110]. Ardisianone, a natural benzoquinone, demonstrated a time-dependent a degradation of survivin and upregulation of cLAP1/2 expression in human refractory prostate cancer (HRPC) cell lines PC-3 and DU-145 following [128]. In a concentration-dependent manner, this molecule inhibited cell proliferation and induced both caspase-dependent and caspase-independent apoptosis via down-regulating Bcl-2 proteins, producing ROS, disrupting the mitochondrial membrane potential and interfering with the PI3K/Akt signaling pathway [128].…”

“…Ardisianone, a natural benzoquinone, demonstrated a time-dependent a degradation of survivin and upregulation of cLAP1/2 expression in human refractory prostate cancer (HRPC) cell lines PC-3 and DU-145 following [128]. In a concentration-dependent manner, this molecule inhibited cell proliferation and induced both caspase-dependent and caspase-independent apoptosis via down-regulating Bcl-2 proteins, producing ROS, disrupting the mitochondrial membrane potential and interfering with the PI3K/Akt signaling pathway [128]. Given its ability to upregulate IAP expression, ardisianone might be a promising candidate for acquired chemotherapy- or IAP-antagonist resistance.…”