Loganic acid regulates the transition between epithelial and mesenchymal-like phenotypes by alleviating MnSOD

Na Young Kim1, In Jin Ha2, Jae-Young Um1

  • 1Department of Science in Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.

Life Sciences
|February 2, 2023
PubMed
Abstract

Insights

LGA effectively suppresses cancer metastasis and epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma by reducing manganese superoxide dismutase (MnSOD) expression. This study highlights LGA as a potential anti-metastatic agent.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cancer metastasis is a primary driver of cancer-related mortality.
  • C-X-C chemokine receptors (CXCRs) and manganese superoxide dismutase (MnSOD) are implicated in metastasis and epithelial-mesenchymal transition (EMT).

Purpose of the Study:

  • To investigate the anti-metastatic potential of LGA.
  • To explore the role of MnSOD in LGA's effect on hepatocellular carcinoma (HCC) metastasis and EMT.

Main Methods:

  • Assessed cell viability, proliferation, invasion, and migration using MTT, BrdU, wound healing, and Boyden chamber assays.
  • Evaluated protein and mRNA levels of CXCR4/7, MMP-2/9, MnSOD, and EMT markers via Western blot, RT-qPCR, and immunocytochemistry.

Main Results:

  • LGA treatment inhibited proliferation, invasion, and migration in HCC cells.
  • LGA down-regulated mesenchymal markers, suppressed MMP-2/9 activity, and attenuated MnSOD-induced EMT phenotypes.
  • Overexpression of MnSOD increased ROS levels, which were reduced by LGA; MnSOD deletion decreased mesenchymal protein levels.

Conclusions:

  • LGA demonstrates significant anti-metastatic properties in HCC.
  • LGA suppresses metastasis and EMT by attenuating MnSOD expression.
  • LGA represents a novel therapeutic candidate for combating hepatocellular carcinoma metastasis.

Related Concept Videos

Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.7K
Liver Regeneration01:24

Liver Regeneration

The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
3.3K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.4K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.2K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K