Amsilarotene

Amsilarotene (TAC-101; Am 555S), an orally active synthetic retinoid, has selective affinity for retinoic acid receptor α (RAR-α) binding with Ki of 2.4, 400 nM for RAR-α and RAR-β. Amsilarotene induces the apoptotic of human gastric cancer, hepatocellular carcinoma and ovarian carcinoma cells. Amsilarotene can be used for the research of cancer[1][2][3].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Metabolic Enzyme/Protease >> RAR/RXR

RARα:2.4 nM (Ki)

RARβ:400 nM (Ki)

Amsilarotene (0, 10, 25 μM; 24 hours) induces apoptosis of human epithelial ovarian carcinoma-derived cell lines in a concentration-dependent manner[2]. Amsilarotene (10, 20 μM; 0, 3, 6, and 9 days) inhibits the proliferation of BxPC-3 and MIAPaCa-2 cells[3]. Amsilarotene (10 μM; 48 hours) increases the proportion of sensitive BxPC-3 cells in the G1 phase[3]. Amsilarotene (10 μM; 0, 3, 6, 24, 48, 72 hours) inhibits the retinoblastoma-gene product (RB) phosphorylation in BxPC-3 cells between 24 and 72 hours[3]. Apoptosis Analysis[2] Cell Line: RMG-I, RMG-II, RTSG, RMUG-S, RMUG-L, and KF cells Concentration: 0, 10, 25 μM Incubation Time: 24 hours Result: Induced apoptosis in a concentration-dependent manner in all of the cell lines, except KF cells. Cell Proliferation Assay[3] Cell Line: BxPC-3, MIAPaCa-2, AsPC-1 cells Concentration: 10 and 20 μM Incubation Time: 0, 3, 6, and 9 days. Result: Inhibited the proliferation of BxPC-3 and MIAPaCa-2 cells, but not the proliferation of AsPC-1 cells. Cell Cycle Analysis[3] Cell Line: Sensitive BxPC-3 cells Concentration: 10 μM Incubation Time: 48 hours Result: The proportion of cells in the G1 phase increased from 43% of untreated control cells to 86%

Amsilarotene (8 mg/kg/day orally for 30 days) inhibits the RMG-II tumor growth in nude mice[2]. Animal Model: 6-week-old female BALB/c nu/nu mice with subcutaneous RMG-II tumors[2] Dosage: 8 mg/kg/day Administration: Orally for 30 days Result: The maximal tumor growth-inhibiting effect was seen on day 31 of administration, when there was a 45% reduction of relative tumor volume (RTV).

[1]. Sun SY, et al. Differential effects of synthetic nuclear retinoid receptor-selective retinoids on the growth of human non-small cell lung carcinoma cells. Cancer Res. 1997 Nov 1;57(21):4931-9.

[2]. Suzuki N, et al. A novel retinoid, 4-[3,5-bis (trimethylsilyl) benzamido] benzoic acid (TAC-101), induces apoptosis of human ovarian carcinoma cells and shows potential as a new antitumor agent for clear cell adenocarcinoma. Gynecol Oncol. 2004 Sep;94(3):643-9.

[3]. Fujimoto K, et al. Induction of cell-cycle arrest and apoptosis by a novel retinobenzoic-acid derivative, TAC-101, in human pancreatic-cancer cells. Int J Cancer. 1999 May 17;81(4):637-44.