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Plant hormones are signal molecules working at low concentrations and produced by plant cells for regulation of plant growth, dormancy, differentiation and stress response. Some plant hormones are known as biologically active compounds affecting the viability, proliferation, differentiation and other functions of animal cells, yet the underlying mechanisms are poorly understood. Therefore the mode of plant hormone action on human normal and pathological cells needs deeper understanding, because it may help to development new approaches for production of specific and less toxic drugs. The aim of our study was to investigate the effect of plant hormones – jasmonic (JA), abscisic (ABA) and gibberellic (GA) acids on cultured human normal and tumor keratinocytes (HaCaT and A431 cell lines). Using MTT test, immunocytochemistry and electron microscopy we showed that in both cell lines sub-toxic concentrations (2mM) of hormones stimulated ER network enlarging and hypertrophy of Golgi complex - predominantly, swelling of trans-Golgi cysternae and trans-Golgi network. Click-It technique showed that the level of total protein synthesis increased in HaCaT cells after JA and in A431 cells after JA and ABA treatment. Investigation of acidic vesicles compartment using fluorescent probes (LysoTracker Red DND-99 and monodansyl cadaverine) and electron microscopy showed that JA and ABA treatment affected this membrane compartment and induced the formation of large autophagic vacuoles and autophagosomes in both HaCaT and A431 cells, while GA – only in A431 cells. The activation of autophagy is one of the hallmarks of early stages of terminal keratinocyte differentiation. Using immunocytochemistry and Western blotting we showed increased expression of keratinocyte differentiation marker involucrin in A431 cells. Thus similar structural response of ER and Golgi indicates that synthetic and secretory system of HaCaT and A431 cells may be the cellular targets for plant hormones. Targeting of these organelles may lead to activation of different cellular processes, such as ER/Golgi stress response in HaCaT and initiation of differentiation in A431 cells.