Evaluation of G2013 (α-L-guluronic acid) efficacy on PC-3 cells through inhibiting the expression of inflammatory factors.
Zahra BagherianAbbas MirshafieyMonireh MohsenzadeganMohammad M FarajollahiPublished in: Clinical and experimental pharmacology & physiology (2021)
Given multiple treatment strategies for prostate cancer, its mortality rate is still high; therefore, novel treatment strategies seem necessary. G2013 or α-L-guluronic acid is a new patented drug with immunomodulatory and anti-inflammatory properties. This study aimed to evaluate the property of G2013 on inflammatory molecules involved in tumorigenesis of prostate cancer. MTT assay was used to assess the effect of the drug on the proliferation of PC-3 cells. Expression of interleukin 8 (IL-8), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), myeloid differentiation factor 88 (MYD-88), cyclooxygenase 2 (COX-2), matrix metalloproteinase-2 (MMP-2), and MMP-9 genes were studied in the PC-3 cells treated with 25 (low dose) or 50 (high dose) µg/mL of G2013 for 24 h using quantitative real-time polymerase chain reaction (qRT-PCR) technique. Protein expression of NF-κB and protein activities of MMP-2 and MMP-9 were assayed using flow cytometry and gelatin zymography, respectively. The expression of COX-2 (p = 0.007 at low dose), MMP-2 (p = 0.023 at low dose, p = 0.002 at high dose), NF-κB (p = 0.004 at low dose) and IL-8 (p < 0.0001 in both doses) genes, NF-κB protein (p < 0.0001 in both doses), and MMP-2 activity (p < 0.0001 in both doses) were significantly reduced in the presence of G2013 as compared to the control group. Cancer cell proliferation was also inhibited under 10-500 µg/mL G2013 treatment. Our results revealed that G2013 has the potential to inhibit PC-3 cell proliferation and reduce the expression of tumour-promoting mediators, COX-2, MMP-2, NF-κB, and IL-8 involved in the progression and metastasis of prostate cancer.
Keyphrases
- low dose
- nuclear factor
- high dose
- prostate cancer
- signaling pathway
- toll like receptor
- poor prognosis
- cell proliferation
- pi k akt
- binding protein
- cell migration
- oxidative stress
- lps induced
- radical prostatectomy
- stem cell transplantation
- flow cytometry
- squamous cell carcinoma
- genome wide
- immune response
- risk factors
- anti inflammatory
- gene expression
- cardiovascular disease
- young adults
- small molecule
- transcription factor
- mass spectrometry
- type diabetes
- high resolution
- risk assessment
- single cell
- amino acid
- cardiovascular events
- dna methylation
- nitric oxide
- protein protein