Gibberellic acid initiates er stress and activation of differentiation in cultured human immortalized keratinocytes hacat and epidermoid carcinoma cells a431

Diterpenoid plant hormone gibberellic acid (GA) plays an important role in regulation of plant growth and development and is commonly used in agriculture for activation of plant growth and food production. It is known that many plant-derived compounds have miscellaneous biological effects on animals and humans, influencing specific cellular functions and metabolic path-ways. However, the effect of GA on animal and human cells remains controversial. We investigated the effect of GA on cultured human cell lines of epidermoid origin—immortalized non-tumorigenic keratinocytes HaCaT and carcinoma A431 cells. We found that at a non-toxic dose, GA upregulated the expression of genes associated with the ER stress response—CHOP, sXBP1, GRP87 in both cell lines, and ATF4 predominantly in A431 cells. We also showed that GA was more effective in upregulating the production of ER stress marker GRP78, autophagy marker LC3B-II, and differentiation markers involucrin and filaggrin in A431 cells than in HaCaT. We conclude that GA induces mild ER stress in both cell lines, followed by the activation of differentiation via upregulation of autophagy. However, in comparison with immortalized keratinocytes HaCaT, GA is more effective in inducing differentiation of carcinoma A431 cells, probably due to the inherently lower differentiation status of A431 cells. The activation of differentiation in poorly differentiated and highly malignant A431 cells by GA may lower the level of malignancy of these cells and decrease their tumorigenic potential. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Authors
Vildanova M.1 , Vishnyakova P. 2, 3 , Saidova A.1 , Konduktorova V.1 , Onishchenko G.1 , Smirnova E. 1
Journal
Publisher
MDPI AG
Number of issue
11
Language
English
Status
Published
Number
1813
Volume
13
Year
2021
Organizations
  • 1 Faculty of Biology, Lomonosov Moscow State University, Leninskie Gory, 1, Bld. 12, Moscow, 119234, Russian Federation
  • 2 Laboratory of Regenerative Medicine, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I, Kulakov of Ministry of Healthcare of Russian Federation, 4 Oparina Street, Moscow, 117997, Russian Federation
  • 3 Histology Department, Peoples’ Friendship, University of Russia (RUDN University), 6 Miklukho-Maklaya Street, Moscow, 117198, Russian Federation
Keywords
Autophagy; Differentiation; Epidermoid carcinoma; ER stress; Gibberellic acid; Human keratinocytes; Plant hormones
Date of creation
16.12.2021
Date of change
16.12.2021
Short link
https://repository.rudn.ru/en/records/article/record/76534/
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