Downregulation of Hyaluronic acid-CD44 signaling pathway in cervical cancer cell by natural polyphenols Plumbagin, Pongapin and Karanjin.

Abstract

Hyaluronic acid (HA)-CD44 pathway showed association with several malignancies. The natural polyphenols Plumbagin, Pongapin and Karanjin showed anti-cancer activities in different tumors including cervical carcinoma. To understand their mechanism of anti-cancer activity, the effect of the compounds on HA-CD44 pathway was analyzed in cervical cancer cell line HeLa. The mRNA expression of three different isoforms of CD44 i.e., CD44s, CD44v3, and CD44v6, was differentially downregulated by the compounds. This was validated by Western blot and immunocytochemical analysis of CD44s.The low molecular weight HA (LMW-HA) showed growth promoting activity in HeLa at low concentration, whereas high molecular weight HA (HMW-HA) had no such effect. The compounds could preferentially downregulate the LMW-HA level in HeLa, as evident in the cell as well as in the cell-free conditioned medium. Concentration-dependent upregulation of HA synthase-2 (HAS2) was seen in the cell by the compounds, whereas differential downregulation of hyalurinidases 1-4 (HYAL 1-4), predominantly HYAL1, were seen. The compounds could also downregulate the downstream target of the pathway p-AKT (T-308) in concentration-dependent manner. Thus, the compounds could attenuate the HA-CD44 pathway in HeLa cell to restrict the tumor growth.

• Authors: Rituparna Roy, Suvra Mandal, Jayanta Chakrabarti, Prosenjit Saha, Chinmay Kumar Panda
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 476 Issue 10 Pg. 3701-3709 (Oct 2021) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 34081254 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Benzopyrans
• CD44 protein, human
• Flavones
• Hyaluronan Receptors
• Naphthoquinones
• Neoplasm Proteins
• pongapin
• Hyaluronic Acid
• karanjin
• plumbagin

Topics

• Benzopyrans (pharmacology)
• Down-Regulation (drug effects)
• Female
• Flavones (pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• HeLa Cells
• Humans
• Hyaluronan Receptors (biosynthesis, genetics)
• Hyaluronic Acid (genetics, metabolism)
• Naphthoquinones (pharmacology)
• Neoplasm Proteins (biosynthesis, genetics)
• Signal Transduction (drug effects, genetics)
• Uterine Cervical Neoplasms (drug therapy, genetics, metabolism, pathology)