Long-term zinc treatment alters the mechanical properties and metabolism of prostate cancer cells

NAVRÁTIL, Jiří; Monika KRATOCHVÍLOVÁ; Martina RAUDENSKÁ; Jan BALVAN; Tomáš VIČAR; Kateřina PETRLÁKOVÁ; Kanako SUZUKI; Lucie JADRNA; Jiri BURSA; Martin KRÄTER; Kyoohyun KIM; Michal MASAŘÍK and Jaromír GUMULEC. Long-term zinc treatment alters the mechanical properties and metabolism of prostate cancer cells. Cancer Cell International. London: BMC, 2024, vol. 24, No 1, p. 1-17. ISSN 1475-2867. Available from: https://dx.doi.org/10.1186/s12935-024-03495-y.

Basic information

Original name

Long-term zinc treatment alters the mechanical properties and metabolism of prostate cancer cells

Authors

NAVRÁTIL, Jiří ORCID (203 Czech Republic, belonging to the institution); Monika KRATOCHVÍLOVÁ (203 Czech Republic, belonging to the institution); Martina RAUDENSKÁ (203 Czech Republic, belonging to the institution); Jan BALVAN (203 Czech Republic, belonging to the institution); Tomáš VIČAR (203 Czech Republic, belonging to the institution); Kateřina PETRLÁKOVÁ (203 Czech Republic, belonging to the institution); Kanako SUZUKI ORCID (392 Japan, belonging to the institution); Lucie JADRNA (203 Czech Republic); Jiri BURSA (203 Czech Republic); Martin KRÄTER (276 Germany); Kyoohyun KIM (276 Germany); Michal MASAŘÍK (203 Czech Republic, belonging to the institution) and Jaromír GUMULEC (203 Czech Republic, belonging to the institution)

Edition

Cancer Cell International, London, BMC, 2024, 1475-2867

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Other information

Language

English

Type of outcome

Article in a journal

Field of Study

30204 Oncology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 5.300 in 2023

RIV identification code

RIV/00216224:14110/24:00137096

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1186/s12935-024-03495-y

UT WoS

001310159400002

EID Scopus

2-s2.0-85203513656

Keywords in English

Mechanobiology; Zinc; Actin; Cytoskeleton; Mitochondria; Vimentin; Metabolism; Cancer

Tags

14110515, 14110518, CF CELLIM, CF NANO, CF PROT, rivok

Tags

International impact, Reviewed

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Abstract

In the original language

The failure of intracellular zinc accumulation is a key process in prostate carcinogenesis. Although prostate cancer cells can accumulate zinc after long-term exposure, chronic zinc oversupply may accelerate prostate carcinogenesis or chemoresistance. Because cancer progression is associated with energetically demanding cytoskeletal rearrangements, we investigated the effect of long-term zinc presence on biophysical parameters, ATP production, and EMT characteristics of two prostate cancer cell lines (PC-3, 22Rv1). Prolonged exposure to zinc increased ATP production, spare respiratory capacity, and induced a response in PC-3 cells, characterized by remodeling of vimentin and a shift of cell dry mass density and caveolin-1 to the perinuclear region. This zinc-induced remodeling correlated with a greater tendency to maintain actin architecture despite inhibition of actin polymerization by cytochalasin. Zinc partially restored epithelial characteristics in PC-3 cells by decreasing vimentin expression and increasing E-cadherin. Nevertheless, the expression of E-cadherin remained lower than that observed in predominantly oxidative, low-invasive 22Rv1 cells. Following long-term zinc exposure, we observed an increase in cell stiffness associated with an increased refractive index in the perinuclear region and an increased mitochondrial content. The findings of the computational simulations indicate that the mechanical response cannot be attributed exclusively to alterations in cytoskeletal composition. This observation suggests the potential involvement of an additional, as yet unidentified, mechanical contributor. These findings indicate that long-term zinc exposure alters a group of cellular parameters towards an invasive phenotype, including an increase in mitochondrial number, ATP production, and cytochalasin resistance. Ultimately, these alterations are manifested in the biomechanical properties of the cells.

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Links

EF18_046/0015974, research and development project	Name: Modernizace České infrastruktury pro integrativní strukturní biologii
LM2018129, research and development project	Name: Národní infrastruktura pro biologické a medicínské zobrazování Czech-BioImaging Investor: Ministry of Education, Youth and Sports of the CR
MUNI/A/1587/2023, interní kód MU	Name: Patofyziologie vybraných komplexních nemocí od molekulární do systémovou úroveň Investor: Masaryk University, Pathophysiology of selected complex diseases from molecular to systemic level
NU22J-08-00062, research and development project	Name: Mechanická a morfologická high-throughput fenotypizace nádorových buněk během smykového napětí: prediktor migračního a invazivního potenciálu Investor: Ministry of Health of the CR, Subprogram 2 - junior
90242, large research infrastructures	Name: CIISB III
90250, large research infrastructures	Name: Czech-BioImaging III
90254, large research infrastructures	Name: e-INFRA CZ II
964997, interní kód MU	Name: Alliance for Life Sciences: From Strategies to Actions in Central and Eastern Europe (Acronym: A4L_ACTIONS) Investor: European Union, Health, demographic change and wellbeing (Societal Challenges)