Microarray data analysis of antileukemic action of Cinnamoylated benzaldehyde LQB-461 in Jurkat cell line

• Published in: Molecular biology reports 2024-12, Vol.51 (1), p.187-187, Article 187
• Main Authors: Thimoteo, Rachell R. C., Neto, Pedro Nicolau, Costa, Debora S. S., da Mota Ramalho Costa, Fabrício, Brito, Douglas Cazaroti, Costa, Paulo R. R., de Almeida Simão, Tatiana, Dias, Ayres G., Justo, Graça
• Format: Article
• Language: English
• Subjects: Animal Anatomy; Animal Biochemistry; Apoptosis; Autophagy; Benzaldehyde; Benzaldehydes; Biomedical and Life Sciences; Caspase-3; Cell cycle; Cell death; Children; Cytotoxicity; Data Analysis; Drug Therapy, Combination; Flow cytometry; G1 phase; Histology; Humans; Imines; Jurkat Cells; Leprostatic Agents; Life Sciences; Morphology; Original Article; Western blotting
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-023-09030-y

Background Leukemias stand out for being the main type of childhood cancer in the world. Current treatments have strong side effects for patients, and there is still a high rate of development of resistance to multidrug therapy. Previously, our research group developed a structure–activity study with novel synthetic molecules analogous to LQB-278, described as an essential molecule with in vitro antileukemic action. Among these analogs, LQB-461 stood out, presenting more significant antileukemic action compared to its derivative LQB-278, with cytostatic and cytotoxicity effect by apoptosis, inducing caspase-3, and increased sub-G1 phase on cell cycle analysis. Methods and results Deepening the study of the mechanism of action of LQB-461 in Jurkat cells in vitro, a microarray assay was carried out, which confirmed the importance of the apoptosis pathway in the LQB-461 activity. Through real-time PCR, we validated an increased expression of CDKN1A and BAX genes, essential mediators of the apoptosis intrinsic pathway. Through the extrinsic apoptosis pathway, we found an increased expression of the Fas receptor by flow cytometry, showing the presence of a more sensitive population and another more resistant to death. Considering the importance of autophagy in cellular resistance, it was demonstrated by western blotting that LQB-461 decreased LC-3 protein expression, an autophagic marker. Conclusions These results suggest that this synthetic molecule LQB-461 induces cell death by apoptosis in Jurkat cells through intrinsic and extrinsic pathways and inhibits autophagy, overcoming some mechanisms of cell resistance related to this process, which differentiates LQB-461 of other drugs used for the leukemia treatment.