TY - JOUR
T1 - Antigiardial activity of acetylsalicylic acid is associated with overexpression of hsp70 and membrane transporters
AU - Ochoa-Maganda, Verónica Yadira
AU - Rangel-Castañeda, Itzia Azucena
AU - Suárez-Rico, Daniel Osmar
AU - Cortés-Zárate, Rafael
AU - Hernández-Hernández, José Manuel
AU - Pérez-Rangel, Armando
AU - Chiquete-Félix, Natalia
AU - León-ávila, Gloria
AU - González-Pozos, Sirenia
AU - Gaona-Bernal, Jorge
AU - Castillo-Romero, Araceli
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/12
Y1 - 2020/12
N2 - Giardia lamblia is a flagellated protozoan responsible for giardiasis, a worldwide diarrheal disease. The adverse effects of the pharmacological treatments and the appearance of drug resistance have increased the rate of therapeutic failures. In the search for alternative therapeutics, drug repositioning has become a popular strategy. Acetylsalicylic acid (ASA) exhibits diverse biological activities through multiple mechanisms. However, the full spectrum of its activities is incompletely understood. In this study we show that ASA displayed direct antigiardial activity and affected the adhesion and growth of trophozoites in a time-dose-dependent manner. Electron microscopy images revealed remarkable morphological alterations in the membrane, ventral disk, and caudal region. Using mass spectrometry and real-time quantitative reverse transcription (qRT-PCR), we identified that ASA induced the overexpression of heat shock protein 70 (HSP70). ASA also showed a significant increase of five ATP-binding cassette (ABC) transporters (giABC, giABCP, giMDRP, giMRPL and giMDRAP1). Additionally, we found low toxicity on Caco-2 cells. Taken together, these results suggest an important role of HSPs and ABC drug transporters in contributing to stress tolerance and protecting cells from ASA-induced stress.
AB - Giardia lamblia is a flagellated protozoan responsible for giardiasis, a worldwide diarrheal disease. The adverse effects of the pharmacological treatments and the appearance of drug resistance have increased the rate of therapeutic failures. In the search for alternative therapeutics, drug repositioning has become a popular strategy. Acetylsalicylic acid (ASA) exhibits diverse biological activities through multiple mechanisms. However, the full spectrum of its activities is incompletely understood. In this study we show that ASA displayed direct antigiardial activity and affected the adhesion and growth of trophozoites in a time-dose-dependent manner. Electron microscopy images revealed remarkable morphological alterations in the membrane, ventral disk, and caudal region. Using mass spectrometry and real-time quantitative reverse transcription (qRT-PCR), we identified that ASA induced the overexpression of heat shock protein 70 (HSP70). ASA also showed a significant increase of five ATP-binding cassette (ABC) transporters (giABC, giABCP, giMDRP, giMRPL and giMDRAP1). Additionally, we found low toxicity on Caco-2 cells. Taken together, these results suggest an important role of HSPs and ABC drug transporters in contributing to stress tolerance and protecting cells from ASA-induced stress.
KW - Acetylsalicylic acid
KW - Giardia lamblia
KW - Heat shock protein 70
KW - Membrane transporter
UR - http://www.scopus.com/inward/record.url?scp=85097058533&partnerID=8YFLogxK
U2 - 10.3390/ph13120440
DO - 10.3390/ph13120440
M3 - Artículo
AN - SCOPUS:85097058533
SN - 1424-8247
VL - 13
SP - 1
EP - 16
JO - Pharmaceuticals
JF - Pharmaceuticals
IS - 12
M1 - 440
ER -