RETRA

RETRA is a RIPK1/RIPK3/MLKL and p73 activator. RETRA mediates plasma membrane disruption, induces ROS accumulation, triggers early mitochondrial hyperpolarization, and synergistically drives necroptosis. RETRA inhibits cancer cells carrying mutant p53 via a p73-dependent salvage pathway. RETRA can be used in research related to cervical cancer and cancers with mutant p53^[1][2]. In Vitro:RETRA (10-100 μM; 24-96 h) inhibits the viability of SiHa and C-33A cervical cancer cells in a concentration- and time-dependent manner^[1].
RETRA (25-100 μM; 24-72 h) inhibits the proliferation of SiHa and C-33A cervical cancer cells in a concentration-dependent manner^[1].
RETRA (25-100 μM; 48 h) induces S-phase cell cycle arrest in SiHa and C-33A cervical cancer cells by regulating cell cycle regulatory proteins, including upregulating p21 and downregulating cyclin D3^[1].
RETRA (25-100 μM; 24, 48, 72 h) selectively induces non-apoptotic cell death in SiHa and C-33A cervical cancer cells, and exhibits no cytotoxicity against normal human peripheral blood mononuclear cells (PBMCs)^[1].
RETRA (50-100 μM; 48 h) induces necroptosis in SiHa, C-33A and CaSki cervical cancer cells via phosphorylation of RIPK1, RIPK3 and MLKL; this cell death is reversible by the necroptosis inhibitor Nec-1 (HY-15760)^[1].
RETRA (25-100 μM; 24, 48 h) induces mitochondrial hyperpolarization in SiHa and C-33A cervical cancer cells in a concentration- and time-dependent manner^[1].
RETRA (25-100 μM; 48 h) induces concentration-dependent ROS accumulation in SiHa and C-33A cervical cancer cells, and this accumulation is attenuated by the necroptosis inhibitor Nec-1^[1].
RETRA (1-10 μM; 14 h) specifically activates p53-dependent transcription reporter gene activity in human cancer cell lines expressing mutant p53 (including A431, SW480 and MDA-MB-231) as well as p53-deficient cell lines reconstituted with mutant p53, but exerts no effect on cells expressing wild-type p53 or p53-deficient cells^[2].
RETRA (1.5 μg/mL; 14 h) selectively induces transcriptional activation of the p53-dependent genes CDKN1A and BBC3 in A431 cells expressing mutant p53^[2].
RETRA (2 μg/mL; 20 h) increases TA/p73 protein levels in A431 cells expressing mutant p53 and releases TA/p73 from the inhibitory complex formed with mutant p53; whereas after treatment at 2 μg/mL for 20 h^[2].
RETRA (0.1-10 μM; 48 h) induces dose-dependent inhibition of cell viability in A431 cells expressing mutant p53, and exhibits enhanced activity in p53-knockdown A431/sh-p53 cells^[2].
RETRA (4 μM; 24 h) specifically inhibits colony formation of A431 and SW480 cells expressing mutant p53, and this effect is partially dependent on the expression of p73; while after treatment with 4 μM for 24 h^[2].
RETRA (1-10 μM) induces dose-dependent activation of caspase 3 and caspase 7 in A431 cells expressing mutant p53, and the activity is enhanced in p53-knockdown A431/sh-p53 cells^[2]. In Vivo:RETRA (0.4 mg/mouse; i.p.; daily; 6 days) suppresses A431 xenograft tumor formation in athymic nu/nu mice, reducing the percentage of tumor-positive injection sites to ~40%^[2].