GS2 Gallium Complex: A Novel Inhibitor of MMP-14 for Anti-Metastatic Cancer Therapy Original paper
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Metals
Metals
Heavy metals play a significant and multifaceted role in the pathogenicity of microbial species.
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Women’s Health
Women’s Health
Women’s health, a vital aspect of medical science, encompasses various conditions unique to women’s physiological makeup. Historically, women were often excluded from clinical research, leading to a gap in understanding the intricacies of women’s health needs. However, recent advancements have highlighted the significant role that the microbiome plays in these conditions, offering new insights and potential therapies. MicrobiomeSignatures.com is at the forefront of exploring the microbiome signature of each of these conditions to unravel the etiology of these diseases and develop targeted microbiome therapies.
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
What Was Studied?
This study examined the effects of [N-(5-chloro-2-hydroxyphenyl)-L-aspartato] chlorogallate (GS2), a water-soluble gallium complex, on tumor cell invasion and the activity and expression of matrix metalloproteinases (MMPs). Specifically, it evaluated GS2’s anti-invasive properties and its regulatory effects on MMP-2, MMP-9, and MMP-14 in two human cancer cell lines: metastatic HT-1080 fibrosarcoma and MDA-MB231 breast carcinoma cells.
Who Was Studied?
The research utilized human cell lines HT-1080 (fibrosarcoma) and MDA-MB231 (breast carcinoma). Additionally, MCF7 cells transfected with MMP-14 and non-transfected fibroblast cells (F40) were used for supplemental experiments.
Most Important Findings
GS2 demonstrated significant anti-invasive and anti-MMP activities at non-cytotoxic concentrations. The compound inhibited MMP-2, MMP-9, and MMP-14 activities in a dose-dependent manner, with IC50 values of 168 µM, 82 µM, and 20 µM, respectively. GS2 reduced the mRNA expression of MMP-14 in both cell lines and inhibited MMP-2 and MMP-9 expression exclusively in MDA-MB231 cells. Western blotting confirmed decreased MMP-14 protein expression in response to GS2. Importantly, GS2 significantly inhibited cell invasion through a type-I collagen-coated matrix, correlating with the downregulation of MMP-14, a critical regulator of the extracellular matrix and tumor invasion. Notably, GS2’s inhibition of MMP-14 showed specificity for cells expressing higher MMP-14 levels, a hallmark of invasive cancer phenotypes.
Greatest Implications
The findings suggest GS2 is a promising candidate for anti-metastatic therapy targeting MMP-14. This is particularly relevant for cancers characterized by elevated MMP-14 expression, such as type II endometrial adenocarcinoma and invasive pituitary adenomas. GS2’s ability to selectively inhibit MMP-14 and reduce cancer cell invasion positions it as a potential therapeutic for limiting tumor metastasis. Moreover, its low cytotoxicity at effective concentrations highlights its clinical applicability.
Matrix Metalloproteinases (MMPs)
Matrix Metalloproteinases (MMPs) are zinc-dependent enzymes that regulate extracellular matrix remodeling, with critical roles in health, disease, and interactions with the microbiome.