RITA (NSC 652287) is a tricyclic thiophene derivative that binds to p53dN (Kd=1.5nM) and blocks the p53-HDM-2 interaction, thereby inhibiting p53 ubiquitination. RITA can be used in research related to various cancers (such as colorectal cancer, renal cancer, cervical cancer, etc.)[1-4].
In vitro, p53-positive tumor cells (e.g., HCT116, MCF-7) were treated with RITA (1–5μM) for 16–24 hours. Under both normoxic and hypoxic conditions, RITA significantly induced p53-dependent apoptosis while downregulating the expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF)[5]. HCT116 ARID1A-/- cells were treated with RITA (0.02–50μM) for 72 hours. RITA significantly induced apoptosis, upregulated the expression of pro-apoptotic genes PUMA and NOXA, and downregulated p21 expression[6].
In vivo, RITA (10mg/kg; once daily) was administered via intraperitoneal injection to BALB/c nude mice bearing HN4-cisR head and neck cancer xenografts for 35 days. RITA alone did not significantly inhibit tumor growth, but when combined with 3-MA, RITA significantly suppressed tumor growth[7]. RITA (10mg/kg; once daily) was administered via intraperitoneal injection to NMRI-nu/nu nude mice bearing Rh36 rhabdomyosarcoma xenografts for 20 days. RITA significantly inhibited the growth of rhabdomyosarcoma xenograft tumors[8].
References:
[1] Issaeva N, Bozko P, Enge M, et al. Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors. Nat Med. 2004 Dec;10(12):1321-8.
[2] Nieves-Neira W, Rivera MI, Kohlhagen G, et al. DNA protein cross-links produced by NSC 652287, a novel thiophene derivative active against human renal cancer cells. Mol Pharmacol. 1999 Sep;56(3):478-84.
[3] Zhao CY, Szekely L, Bao W, et al. Rescue of p53 function by small-molecule RITA in cervical carcinoma by blocking E6-mediated degradation. Cancer Res. 2010 Apr 15;70(8):3372-81. doi: 10.1158/0008-5472.CAN-09-2787. Erratum in: Cancer Res. 2017 Jul 1;77(13):3719.
[4] Gottlieb A, Althoff K, Grunewald L, et al. RITA displays anti-tumor activity in medulloblastomas independent of TP53 status. Oncotarget. 2017 Apr 25;8(17):27882-27891.
[5] Yang J, Ahmed A, Poon E, et al. Small-molecule activation of p53 blocks hypoxia-inducible factor 1alpha and vascular endothelial growth factor expression in vivo and leads to tumor cell apoptosis in normoxia and hypoxia. Mol Cell Biol. 2009 Apr;29(8):2243-53.
[6] Wang Z, Zhang X, Luo Y, et al. Therapeutic targeting of ARID1A-deficient cancer cells with RITA (Reactivating p53 and inducing tumor apoptosis). Cell Death Dis. 2024 May 29;15(5):375.
[7] Shin D, Kim EH, Lee J, et al. RITA plus 3-MA overcomes chemoresistance of head and neck cancer cells via dual inhibition of autophagy and antioxidant systems. Redox Biol. 2017 Oct;13:219-227.
[8] Azatyan A, Gallo-Oller G, Diao Y, et al. RITA downregulates Hedgehog-GLI in medulloblastoma and rhabdomyosarcoma via JNK-dependent but p53-independent mechanism. Cancer Lett. 2019 Feb 1;442:341-350.
RITA (NSC 652287)是一种三环噻吩衍生物，可结合p53dN（Kd=1.5nM）并阻断p53-HDM-2相互作用，抑制p53泛素化。RITA可用于多种癌症（如结直肠癌、肾癌、宫颈癌等）的相关研究[1-4]。
在体外，RITA（1-5μM）处理p53阳性肿瘤细胞（如HCT116、MCF-7等）16-24小时。在常氧和缺氧条件下，RITA显著诱导p53依赖性细胞凋亡，同时下调缺氧诱导因子1α（HIF-1α）和血管内皮生长因子（VEGF）的表达[5]。RITA（0.02–50μM）处理HCT116 ARID1A-/-细胞72小时。RITA显著诱导细胞凋亡，同时上调促凋亡基因PUMA和NOXA的表达并下调p21表达[6]。
在体内，RITA（10mg/kg；每天一次）腹腔注射，用于处理携带HN4-cisR头颈癌异种移植的BALB/c裸鼠，连续35天。RITA单独使用对肿瘤生长没有显著抑制作用，但与3-MA联合使用时显著抑制肿瘤生长[7]。RITA（10mg/kg；每天一次）腹腔注射于携带Rh36横纹肌肉瘤异种移植的NMRI-nu/nu裸鼠，连续20天。RITA显著抑制了横纹肌肉瘤异种移植肿瘤的生长[8]。