Downregulation of Hyaluronic acid-CD44 signaling pathway in cervical cancer cell by natural polyphenols Plumbagin, Pongapin and Karanjin.
Mol Cell Biochem
; 476(10): 3701-3709, 2021 Oct.
Article
em En
| MEDLINE
| ID: mdl-34081254
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Benzopiranos
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Transdução de Sinais
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Regulação para Baixo
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Regulação Neoplásica da Expressão Gênica
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Neoplasias do Colo do Útero
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Naftoquinonas
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Receptores de Hialuronatos
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Flavonas
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Ácido Hialurônico
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Proteínas de Neoplasias
Limite:
Female
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Humans
Idioma:
En
Revista:
Mol Cell Biochem
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Índia