Vernodalin Suppresses Tumor Proliferation and Increases Apoptosis of Gastric Cancer Cells Through Attenuation of FAK/PI3K/AKT/mTOR and MAPKs Signaling Pathways.

Abstract

BACKGROUND:

Gastric cancer (GC) is the most aggressive malignant tumor with limited treatment alternatives post metastasis. Vernodalin (VN) induced apoptosis has been reported in various types of human cancer cells. However, the precise molecular mechanisms underlying the anti-metastasis action of VN on GC cells are yet to be elucidated.

OBJECTIVE:

In this study, we investigated the anti-metastatic and apoptotic effects of VN on SGC- 7901 and AGS cells, with a purpose of gaining a deeper understanding of the anti-metastatic mechanisms of VN on gastric carcinoma. To attenuate the activation of PI3K/AKT/mTOR and mitogen-activated protein kinase (MAPK) signaling pathways by VN in GC cells.

METHODS:

We employed VN and gastric cancer cells in experiments such as MTT assay, apoptosis, MMP, DAPI, Rh-123, cell adhesion assay, and western blot analysis on GC SGC-7901 and AGS cells.

RESULTS:

Our results revealed that VN inhibits cell proliferation, adhesion, and metastasis and induces apoptosis of both GC cells. VN potentially reduced the protein expressions of MMP-2, MMP-9, and uPA, whereas intensified expressions of TIMP-1 and TIMP-2. Also, VN attenuates the expression of FAK, p-PI3K, p-AKT, p-mTOR, p-JNK, p-p38MAPK, and p-ERK. Thus, it is inferred that VN treatment reduced the activities of MMP-2 and MMP-9 via the FAK/PI3K/AKT/ mTOR, and MAPKs signaling pathways. Our results confirm that VN prevented GC growth, invasion and metastasis and induce apoptosis in GC cells.

CONCLUSION:

Our findings suggest that VN is a potential natural therapeutic compound as a new remedy for GC chemotherapy treatment.

• Authors: Ying Luo, Dan Zhang, Leping Hou, Nengming Lin
• Journal: Current pharmaceutical biotechnology (Curr Pharm Biotechnol) Vol. 24 Issue 5 Pg. 708-717 ( 2023) ISSN: 1873-4316 [Electronic] Netherlands
• PMID: 35909270 (Publication Type: Journal Article)
• Copyright: Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Chemical References

• Proto-Oncogene Proteins c-akt
• Phosphatidylinositol 3-Kinases
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9
• vernodalin
• TOR Serine-Threonine Kinases
• MTOR protein, human

Topics

• Humans
• Stomach Neoplasms (pathology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction
• Phosphatidylinositol 3-Kinases (metabolism)
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• TOR Serine-Threonine Kinases (metabolism, therapeutic use)
• Apoptosis
• Cell Proliferation
• Cell Line, Tumor
• Cell Movement