Aldehyde Dehydrogenase 1B1 Is Associated with Altered Cell Morphology, Proliferation, Migration and Chemosensitivity in Human Colorectal Adenocarcinoma Cells

• Published in: Biomedicines Vol. 9; no. 1; p. 44
• Main Authors: Tsochantaridis, Ilias, Roupas, Angelos, Voulgaridou, Georgia-Persephoni, Giatromanolaki, Alexandra, Koukourakis, Michael I, Panayiotidis, Mihalis I, Pappa, Aglaia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06-01-2021; MDPI
• Subjects: 5-Fluorouracil; Adenocarcinoma; Aldehyde dehydrogenase; ALDH; ALDH1B1; Antibodies; Apoptosis; Cancer; Carboxylic acids; Cell adhesion & migration; Cell cycle; Cell growth; Cell migration; Cell morphology; Cell proliferation; Colon cancer; Cytology; Dehydrogenases; Doxorubicin; E-cadherin; Enzymes; Etoposide; Flow cytometry; Gene expression; Green fluorescent protein; HT29; Mesenchyme; Morphology; NAD; Oxidation; p53 Protein; Penicillin; Solid tumors; Stem cells; Synchronization; Tumorigenesis; Vimentin; United States > US; ALDH; HT29; chemoresistance; ALDH1B1; aldehyde dehydrogenase; cell proliferation; cell cycle; migration; cancer; cell morphology
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines9010044

Aldehyde dehydrogenases (ALDHs) are NAD(P)
-dependent enzymes that catalyze the oxidation of endogenous and exogenous aldehydes to their corresponding carboxylic acids. ALDHs participate in a variety of cellular mechanisms, such as metabolism, cell proliferation and apoptosis, as well as differentiation and stemness. Over the last few years, ALDHs have emerged as cancer stem cell markers in a wide spectrum of solid tumors and hematological malignancies. In this study, the pathophysiological role of ALDH1B1 in human colorectal adenocarcinoma was investigated. Human colon cancer HT29 cells were stably transfected either with human green fluorescent protein (GFP)-tagged ALDH1B1 or with an empty lentiviral expression vector. The overexpression of ALDH1B1 was correlated with altered cell morphology, decreased proliferation rate and reduced clonogenic efficiency. Additionally, ALDH1B1 triggered a G2/M arrest at 24 h post-cell synchronization, probably through p53 and p21 upregulation. Furthermore, ALDH1B1-overexpressing HT29 cells exhibited enhanced resistance against doxorubicin, fluorouracil (5-FU) and etoposide. Finally, ALDH1B1 induced increased migratory potential and displayed epithelial-mesenchymal transition (EMT) through the upregulation of
and
and the consequent downregulation of
Taken together, ALDH1B1 confers alterations in the cell morphology, cell cycle progression and gene expression, accompanied by significant changes in the chemosensitivity and migratory potential of HT29 cells, underlying its potential significance in cancer progression.