A novel methuosis inducer DZ-514 possesses antitumor activity via activation of ROS-MKK4-p38 axis in triple negative breast cancer

KIZ OpenIR > 科研部门 > 肿瘤生物学（陈策实）

	A novel methuosis inducer DZ-514 possesses antitumor activity via activation of ROS-MKK4-p38 axis in triple negative breast cancer
	Wang, LZ; Mi, DZ; Hu, JH; Liu, WJ; Zhang, Y; Wang, CY; Chen, YH; Chen, CS
	2023
发表期刊	CANCER LETTERS
ISSN	0304-3835
卷号	555
摘要	Triple-negative breast cancer (TNBC) is one of the most malignant tumors with poor prognosis. Methuosis is a new type of nonapoptotic cell death characterized by the accumulation of cytoplasmic vacuoles. In this study, we synthesized and screened a series of N-phenyl-4-pyrimidinediamine derivatives in TNBC cells, finding that DZ514 was the best compound with high toxicity independent of the inhibition of BCL6. DZ-514 decreased cell viability, inhibited cell cycle progression, and induced caspase-independent cell death in TNBC cells. Interestingly, DZ-514 induced cytoplasm vacuolation, which could be blocked by Baf A1, the V-ATPase inhibitor. Furthermore, we found that DZ-514-induced vacuoles were derived from macropinosomes rather than autophagosomes. Most importantly, methuosis induced by DZ-514 was partially mediated by activating the ROSMKK4-p38 axis. Finally, we demonstrated that DZ-514 significantly inhibited tumor growth in an HCC1806 xenograft mouse model. These findings revealed that the novel methuosis inducer DZ-514 could be developed for TNBC treatment.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14179
专题	科研部门_肿瘤生物学（陈策实）
推荐引用方式 GB/T 7714	Wang, LZ,Mi, DZ,Hu, JH,et al. A novel methuosis inducer DZ-514 possesses antitumor activity via activation of ROS-MKK4-p38 axis in triple negative breast cancer[J]. CANCER LETTERS,2023,555.
APA	Wang, LZ.,Mi, DZ.,Hu, JH.,Liu, WJ.,Zhang, Y.,...&Chen, CS.(2023).A novel methuosis inducer DZ-514 possesses antitumor activity via activation of ROS-MKK4-p38 axis in triple negative breast cancer.CANCER LETTERS,555.
MLA	Wang, LZ,et al."A novel methuosis inducer DZ-514 possesses antitumor activity via activation of ROS-MKK4-p38 axis in triple negative breast cancer".CANCER LETTERS 555(2023).

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