TY - JOUR
T1 - Exclusive modifications of NuMA in malignant epithelial cells
T2 - A potential therapeutic mechanism
AU - Cohen-Armon, Malka
N1 - Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/5
Y1 - 2022/5
N2 - NuMA (nuclear mitotic apparatus) protein is indispensable in the mitosis of human proliferating cells, both malignant and benign. The progression of mitosis requires stable spindles, which depend on the bipolar clustering of NuMA within the spindles. The phenanthridine PJ34 kills malignant epithelial cells during mitosis and targets NuMA. PJ34 treated healthy cells are not impaired. PJ34 exclusively blocks the post-translational modification of NuMA in a variety of malignant epithelial cells, but not in benign cells. This blockage of the post-translational modification of NuMA affects its protein-binding capacity, causing construction faults in the mitotic spindle poles of PJ34-treated cancer cells, leading to Mitotic Catastrophe cell death. PJ34 is a potent PARP1 inhibitor. Therefore its PARP independent exclusive cytotoxicity in human malignant cells, challenges the currently accepted notion that inhibition of PARP1 halts cancer by preventing DNA repair. Certain molecules that act as PARP1 inhibitors kill cancer cells by targeting other proteins and vital mechanisms.
AB - NuMA (nuclear mitotic apparatus) protein is indispensable in the mitosis of human proliferating cells, both malignant and benign. The progression of mitosis requires stable spindles, which depend on the bipolar clustering of NuMA within the spindles. The phenanthridine PJ34 kills malignant epithelial cells during mitosis and targets NuMA. PJ34 treated healthy cells are not impaired. PJ34 exclusively blocks the post-translational modification of NuMA in a variety of malignant epithelial cells, but not in benign cells. This blockage of the post-translational modification of NuMA affects its protein-binding capacity, causing construction faults in the mitotic spindle poles of PJ34-treated cancer cells, leading to Mitotic Catastrophe cell death. PJ34 is a potent PARP1 inhibitor. Therefore its PARP independent exclusive cytotoxicity in human malignant cells, challenges the currently accepted notion that inhibition of PARP1 halts cancer by preventing DNA repair. Certain molecules that act as PARP1 inhibitors kill cancer cells by targeting other proteins and vital mechanisms.
KW - Human malignant epithelial cells
KW - Mitotic catastrophe cell death
KW - Mitotic spindle
KW - NuMA
KW - PARP1 inhibitors
KW - PJ34
UR - http://www.scopus.com/inward/record.url?scp=85124815550&partnerID=8YFLogxK
U2 - 10.1016/j.drudis.2022.02.002
DO - 10.1016/j.drudis.2022.02.002
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C2 - 35143964
AN - SCOPUS:85124815550
SN - 1359-6446
VL - 27
SP - 1205
EP - 1209
JO - Drug Discovery Today
JF - Drug Discovery Today
IS - 5
ER -