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A series of ligustrazine platinum(IV) complexes with potent anti-proliferative and anti-metastatic properties that exert chemotherapeutic and immunotherapeutic effects.
- Source :
- Dalton Transactions: An International Journal of Inorganic Chemistry; 10/7/2023, Vol. 52 Issue 37, p13097-13109, 13p
- Publication Year :
- 2023
-
Abstract
- The development of novel anticancer drugs with antiproliferative and antimetastatic activities is of great importance in the pharmaceutical field. Herein, a series of ligustrazine (LSZ) platinum(IV) complexes with chemotherapeutic and immunotherapeutic effects were designed, prepared and evaluated as antitumor agents for the first time. Complex 4 with potent antitumor activities both in vitro and in vivo was screened out as a candidate. Notably, it displays significantly more effective anti-metastatic activities than the platinum(II) drugs cisplatin and oxaliplatin. Mechanism detection discloses that it causes serious DNA damage and increases the expression of γ-H2AX and P53. Then, the apoptosis of tumor cells is promoted by activating the mitochondrial apoptotic pathway Bcl-2/Bax/caspase-3 and causing autophagy via modulating LC3-I/II and P62 expression. Furthermore, the immune therapeutic responses are significantly elevated by blocking HIF-1α, ERK 1/2 and COX-2 pathways to reduce PD-L1 expression, and further increasing CD3<superscript>+</superscript> and CD8<superscript>+</superscript> T cells to elevate T cell immunity in tumors. Tumor metastasis is blocked by the synergistic functions of DNA damage, hypoxia modulation and immune activation. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14779226
- Volume :
- 52
- Issue :
- 37
- Database :
- Complementary Index
- Journal :
- Dalton Transactions: An International Journal of Inorganic Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 172334034
- Full Text :
- https://doi.org/10.1039/d3dt02358c