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The molecular mechanism of a novel derivative of BTO-956 induced apoptosis in human myelomonocytic lymphoma cells.
- Source :
-
Apoptosis : an international journal on programmed cell death [Apoptosis] 2021 Apr; Vol. 26 (3-4), pp. 219-231. Date of Electronic Publication: 2021 Mar 18. - Publication Year :
- 2021
-
Abstract
- Acute myeloid leukemia (AML) is a malignant cancer of the hematopoietic system. Although the effectiveness of arsenic compounds has been recognized and applied clinically, some patients are still found resistant to this chemotherapy. In this study, we investigated that a synthetic thyroid hormone analog (TA), 2-iodo-4-nitro-1-(o-tolyloxy) benzene, had a strong apoptosis effect on U937 cells. U937 cells were treated with TA, and examinted the generation of reactive oxygen species (ROS), dysfunction of mitochondria, expression of pro-apoptosis and anti-apoptosis, and cleavage of caspase-3 and Poly (ADP-ribose) polymerase (PARP). Further, it is also evaluated that insight molecular mechanism and signaling pathways involved in the study. It is found that TA significantly induced apoptosis in U937 cells through production of ROS, dysfunction of mitochondria, and activation of caspase cascade. It was also observed that MAPK signaling pathway including ERK, JNK, and P38 signals are involved in the induction of apoptosis. Moreover, marked activation of autophagy and ER stress markers such as LC3, P62, Beclin1 and GRP78, CHOP were observed, respectively. Pretreatment with ER stress inhibitor tauroursodeoxycholic acid (TUDCA) and autophagy inhibitor 3-Methyladenine (3-MA) have successfully attenuated and aggravated TA-induced apoptosis, respectively. We further confirmed the active involvement of ER stress and autophagy signals. In conclusion, TA induced apoptosis through ER stress and activation of autophagy, and the latter is not conducive to TA-induced cell death. Our results may provide a new insight into the strategic development of novel therapy for the treatment of AML.
- Subjects :
- Autophagy drug effects
Cell Line, Tumor drug effects
Endoplasmic Reticulum Chaperone BiP
Endoplasmic Reticulum Stress drug effects
Humans
MAP Kinase Signaling System drug effects
Reactive Oxygen Species metabolism
U937 Cells
Apoptosis drug effects
Iodobenzoates pharmacology
Leukemia, Myeloid drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1573-675X
- Volume :
- 26
- Issue :
- 3-4
- Database :
- MEDLINE
- Journal :
- Apoptosis : an international journal on programmed cell death
- Publication Type :
- Academic Journal
- Accession number :
- 33738673
- Full Text :
- https://doi.org/10.1007/s10495-021-01664-2