TY - JOUR
T1 - Antilymphoma effect of incomptine a
T2 - In vivo, in silico, and toxicological studies
AU - Calzada, Fernando
AU - Bautista, Elihú
AU - Hidalgo-Figueroa, Sergio
AU - García-Hernández, Normand
AU - Barbosa, Elizabeth
AU - Velázquez, Claudia
AU - Ordoñez-Razo, Rosa María
AU - Arietta-García, Angel Giovanni
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - Incomptine A (IA) is a sesquiterpene lactone isolated from Decachaeta incompta that induces apoptosis, reactive oxygen species production, and a differential protein expression on the U-937 (diffuse histiocytic lymphoma) cell line. In this work, the antitumor potential of IA was investi-gated on Balb/c mice inoculated with U-937 cells and through the brine shrimp lethality (BSL) test. Furthermore, IA was subjected to molecular docking study using as targets proteins associated with processes of cancer as apoptosis, oxidative stress, and glycolytic metabolism. In addition to determining the potential toxicity of IA in human, its acute toxicity was performed in mice. Results reveals that IA showed high antilymphoma activity and BSL with an EC50 of 2.4 mg/kg and LC50 16.7 µg/mL, respectively. The molecular docking study revealed that IA has strong interaction on all targets used. In the acute oral toxicity, IA had a LD50 of 149 mg/kg. The results showed that the activities of IA including antilymphoma activity, BSL, acute toxicity, and in silico interactions were close to the methotrexate, an anticancer drug used as positive control. These findings suggest that IA may serve as a candidate for the development of a new drug to combat lymphoma.
AB - Incomptine A (IA) is a sesquiterpene lactone isolated from Decachaeta incompta that induces apoptosis, reactive oxygen species production, and a differential protein expression on the U-937 (diffuse histiocytic lymphoma) cell line. In this work, the antitumor potential of IA was investi-gated on Balb/c mice inoculated with U-937 cells and through the brine shrimp lethality (BSL) test. Furthermore, IA was subjected to molecular docking study using as targets proteins associated with processes of cancer as apoptosis, oxidative stress, and glycolytic metabolism. In addition to determining the potential toxicity of IA in human, its acute toxicity was performed in mice. Results reveals that IA showed high antilymphoma activity and BSL with an EC50 of 2.4 mg/kg and LC50 16.7 µg/mL, respectively. The molecular docking study revealed that IA has strong interaction on all targets used. In the acute oral toxicity, IA had a LD50 of 149 mg/kg. The results showed that the activities of IA including antilymphoma activity, BSL, acute toxicity, and in silico interactions were close to the methotrexate, an anticancer drug used as positive control. These findings suggest that IA may serve as a candidate for the development of a new drug to combat lymphoma.
KW - Acute toxicity
KW - Antilymphoma activity
KW - Brine shrimp lethality
KW - Cancer
KW - Incomptine A
KW - Molecular docking
KW - Non-Hodgkin lymphoma
UR - http://www.scopus.com/inward/record.url?scp=85118580005&partnerID=8YFLogxK
U2 - 10.3390/molecules26216646
DO - 10.3390/molecules26216646
M3 - Artículo
C2 - 34771055
AN - SCOPUS:85118580005
SN - 1420-3049
VL - 26
JO - Molecules
JF - Molecules
IS - 21
M1 - 6646
ER -