Juxtamembrane 2 mimic peptide competitively inhibits mitochondrial trafficking and activates ROS-mediated apoptosis pathway to exert anti-tumor effects

Our previous study demonstrates that a juxtamembrane 2 (JM2) mimic peptide can inhibit proliferation and induce apoptosis of tumor cells. However, the mechanism remains unclear. In this study, JM2 is found to suppress the growth of 4T1 breast tumors by inducing apoptosis and inhibiting the prolifera...

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Bibliographic Details
Published in:Cell death & disease 2022-03, Vol.13 (3), p.264-13, Article 264
Main Authors: He, Dan, Ma, Zhijie, Xue, Ke, Li, Haiyan
Format: Article
Language:English
Subjects:
13/1
13/2
13/31
14/19
14/34
38/77
631/154/51/2308
631/61/54/990
631/67/1347
631/80/82/23
64/60
692/699/67/1059/99
Antibodies
Apoptosis
Biochemistry
Biomedical and Life Sciences
Breast cancer
Breast Neoplasms - pathology
Cell Biology
Cell Culture
Cell cycle
Cell Line, Tumor
Cell Proliferation
Female
Humans
Hyaluronic acid
Hydrogels
Hydrogels - pharmacology
Immunology
Life Sciences
Membrane Potential, Mitochondrial
Mitochondria
Mitochondria - metabolism
Peptides
Peptides - metabolism
Peptides - pharmacology
Reactive Oxygen Species - metabolism
S phase
Tumor cells
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Summary:Our previous study demonstrates that a juxtamembrane 2 (JM2) mimic peptide can inhibit proliferation and induce apoptosis of tumor cells. However, the mechanism remains unclear. In this study, JM2 is found to suppress the growth of 4T1 breast tumors by inducing apoptosis and inhibiting the proliferation of 4T1 tumor cells. Further study indicates that JM2 can stimulate the mitochondria to gather near the microtubule-organizing center of tumor cells and subsequently induce ROS-induced ROS release responses, which results in mitochondrial dysfunction and mitochondria-mediated apoptosis. In addition, JM2 can arrest cell cycle in S phase by regulating the expression of cell cycle-related proteins and consequently inhibit proliferation of tumor cells. Then, a previously designed JM2 grafted hyaluronic acid (HA) injectable hydrogel system (HA-JM2) is injected in a breast tumor-resected model and the HA-JM2 hydrogel can inhibit the malignant proliferation of residual tumor cells and suppress the breast tumor recurrence. These findings not only confirm the application potentials of JM2 in anti-tumor therapy and tumor post-surgery treatments but also provide greater understanding on the mechanisms by which JM2 inhibits tumor growth.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-022-04639-6