Gibberellic acid induces autophagy and differentiation in human epidermoid carcinoma cell line A431 via activation of endoplasmic reticulum stress

Vildanova, M.S.; Vishnyakova, P.A.; Turishcheva, E.P.; Saidova, A.A.; Konduktorova, V.V.; Potashnikova, D.M.; Onishchenko, G.E.; Smirnova, E.A.

Авторы: Vildanova M.S., Vishnyakova P.A., Turishcheva E.P., Saidova A.A., Konduktorova V.V., Potashnikova D.M., Onishchenko G.E., Smirnova E.A.
Сборник: МЕЖДУНАРОДНАЯ КОНФЕРЕНЦИЯ «MOLECULAR MECHANISMS OF AUTOPHAGY IN DISEASES». 30-31 ОКТЯБРЯ 2020 ГОДА, САНКТ-ПЕТЕРБУРГ – СБОРНИК ТЕЗИСОВ – : 2020. – 48 С
Тезисы
Год издания: 2020
Место издания: СПБ
Первая страница: 42
Последняя страница: 42
Аннотация: ObjectivePlant hormones and their natural and synthetic derivatives are promising objects ofinvestigation, because they impact viability and metabolism of human cells. Plant hormonegibberellic acid (gibberellin A3) (GA), potent plant growth regulator, is commonly used inagriculture. It turned out that GA can have different effects on the cells of animals and humans,depending on the object of study, concentrations, and application regimen. Many studies reportthe toxic, carcinogenic and allergic effects of GA, but emerging evidence indicates that GA andits derivatives may cause anti-inflammatory and anti-tumor activity, stimulation of secretion.Materials and methodsThis work was aimed to investigate the possibility of ER stress activation by GA and toreveale the differences in the responses to GA of human cultured immortalized non-tumorigenicHaCaT and epidermoid carcinoma A431 cells. We researched the effect of GA (2 mM, 24 hours)on both cell lines. Using flow cytometry and Annexin V/propidium iodide labeling, we found thatGA does not affect cellular viability and proliferation. RT-qPCR showed that GAenhances/elevates the expression of genes associated with ER stress - GRP78 and CHOP inHaCaT cells, and GRP78, ATF4, and CHOP in A431 cells. Intracellular Ca2+ concentration wasassayed by the Fluo-4 AM calcium probe. The addition of GA was accompanied by the influx ofintracellular Ca2+ in both cell lines. However, Western blot analysis showed that the content ofER stress marker GRP78 increased only in A431 cells. Mild ER stress can activate of autophagy(Rashid et al., 2015) and cellular differentiation (Mahanty et al., 2019). The increased content ofautophagy marker LC3B-II was revealed only in GA-treated A431 cells. Using transmissionelectron microscopy, we showed the different phases of autophagic flux (autophagosomes andautolysosomes) in control and GA-treated A431 cells.Results and conclusionsIt demonstrates the progression of autophagic flux without arrest in the early stages.Immunocytochemical staining and Western blot analysis demonstrated that GA selectivelyincreased the level of keratinocytes differentiation markers: involucrin - only in A431 cells, andfilaggrin – in both cell lines. Additionally, normalization of involucrin staining was observed inA431 cells. Thus we demonstrated for the first time that plant hormone GA induced mild ERstress with different outcomes for normal and tumor cells: adaptive response is manifested inboth HaCaT and A431 cells, but autophagy and differentiation – only in A431 cells.References[1] Mahanty S, Dakappa SS, Shariff R, Patel S, Swamy MM, Majumdar A, et al. Keratinocytedifferentiation promotes ER stress-dependent lysosome biogenesis. Cell Death Dis.2019;10(4): 269.[2] Rashid HO, Yadav RK, Kim HR, Chae HJ. ER stress: Autophagy induction, inhibition andselection. Autophagy. 2015;11(11):1956–77.
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Gibberellic acid induces autophagy and differentiation in human epidermoid carcinoma cell line A431 via activation of endoplasmic reticulum stressтезисы доклада Тезисы

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