Prostate Apoptotic Induction and NFκB Suppression by Dammarolic Acid: Mechanistic Insight into Onco-Therapeutic Action of an Aglycone Asiaticoside

Abstract

Prostate cancer (PCa) is addressed as the second most common form of onco-threat worldwide and is usually considered as the major cause of mortality in men. Recent times have seen a surge in exploration of plant-derived components for alternative therapeutical interventions against different oncological malignancies. Dammarolic acid or Asiatic acid (AsA) is an aglycone asiaticoside that has been reported for its efficacy in several ailments including cancer. The current study aimed to investigate the anti-proliferative potency of AsA against human prostate cancer PC-3 cells. Purified AsA was diluted and PC-3 cells were exposed to 20, 40, and 80 µM concentration and incubated for 24 h. Post-exposure, PC-3 cells showcased a substantial loss of their viability at 20 µM (p < 0.05), moreover, this reduction in cell viability escalated proportionally with an increase in AsA at concentrations of 40 and 80 µM (p < 0.01; p < 0.001) respectively. AsA-impelled loss of cellular viability was also evident from the acridine orange-stained photomicrographs, which was also used to quantify the viable and apoptotic cells using Image J software. Additionally, quantification of ROS within PC-3 cells also exhibited an increase in DCF-DA-mediated fluorescence intensity post-exposure to AsA in a dose-dependent manner. AsA-induced apoptosis in PC-3 cells was shown to be associated with augmented activity of caspase-3 proportionally to the AsA concentrations. Thus, initially, this exploratory study explicated that AsA treatment leads to anti-proliferative effects in PC-3 cells by enhancing oxidative stress and inciting apoptosis en route to onset of nuclear fragmentation.

RUNX1 Upregulation Causes Mitochondrial Dysfunction via Regulating the PI3K-Akt Pathway in iPSC from Patients with Down Syndrome

“…1A and 1B, a , a high green fluorescence intensity was noted in the DS-iPSCs. The quantification of green fluorescence intensity was analyzed by ImageJ ( Alafnan et al, 2021 ), and the results suggested that the contents of ROS were increased 2.24-fold in DS-iPSCs (0.076 ± 0.004 vs 0.034 ± 0.003; P < 0.0001). The ATP contents in DS-iPSCs were 1.68-fold lower than those in N-iPSCs (3.95 ± 0.39 vs 6.64 ± 0.17; P = 0.0029) ( Fig.…”

“…Our previous study demonstrated that the expression levels of almost all the genes related to mitochondrial function were downregulated in DS-iPSCs, suggesting that mitochondria were dysfunctional in these cells (Qiu et al, 2017) was analyzed by ImageJ (Alafnan et al, 2021), and the results suggested that the contents of ROS were increased 2.24-fold in DS-iPSCs (0.076 ± 0.004 vs 0.034 ± 0.003; P < 0.0001). The ATP contents in DS-iPSCs were 1.68-fold lower than those in N-iPSCs (3.95 ± 0.39 vs 6.64 ± 0.17; P = 0.0029) (Fig.…”

Cucurbitacin-B Exerts Anticancer Effects through Instigation of Apoptosis and Cell Cycle Arrest within Human Prostate Cancer PC3 Cells via Downregulating JAK/STAT Signaling Cascade

“…Thus, it may be concluded that due to the decrease in cyclinD1 and CDK4 expression, Cur-B would have also resulted in limiting the progression of PC-3 cells at the G0/G1 phase, further explaining the anticancer efficacy of Cur-B against PC-3 cells. Contrastingly, CDK inhibitors or CDKIs such as p21Cip1 and p27Kip1 have also been reported for their regulatory role in restraining the entry of cells in the S phase of the cell cycle by impeding the kinase activity of complexes formed between cyclins and CDKs [ 32 , 37 ]. We also found that p21Cip1mRNA levels were significantly increased, thereby subsequently affirming the notion that Cur-B would have also resulted in limiting the progression of PC-3 cells at the G0/G1 phase.…”

“…Instigation of apoptosis within PC-3 cells exposed to Cur-B at stated concentrations was assessed by acridine orange (AO) and ethidium bromide (EtBr) as earlier reported [ 14 , 37 ]. Approximately 5 × 10 5 PC-3 cells/well were incubated overnight for adherence in a 96-well plate.…”

Advances in Molecular Regulation of Prostate Cancer Cells by Top Natural Products of Malaysia

“…The cytotoxicity of C. asiatica extracts and its characteristic compound Asiatic acid-also known as dammarolic acid (Figure 2)-have been reported to induce apoptosis in PC3 cells (20-80 µM, 24 h), with an increase in intracellular ROS and activity of caspase-3 as well as nuclear fragmentation [232]. In addition, this compound has been previously reported to deploy cytotoxicity to other tumor cells.…”