Cell lines

Mouse melanoma cell line(B16F10)

Preparation Method

B16F10 cells were incubated with Remodelin and α- melanocyte - stimulating hormone (α-MSH) for 3 days. The harvested cells or media were centrifuged and the pellets were solubilized in sodium hydroxide for 1h. The melanin contents were measured using spectrophotometer at 475 nm wavelength (OD475).

Reaction Conditions

10, 20 μM Remodelin for 3 days.

Applications

α-MSH-mediated increase in the extracellular and intracellular melanin contents was significantly decreased upon treatment with 20 μM remodelin.Remodelin attenuates melanin synthesis by repressing MITF.

Animal models

BALB/c nu/nu mice

Preparation Method

AR-negative prostate Cancer Cells (PC-3 cells) were inoculated into the armpits of mice by subcutaneous injection. One week later, Remodelin injection was performed every two days for a total of 4 weeks. Tumor size was measured every two days. Tumors were excised from nude mice and weighed after 4 weeks.

Dosage form

2,20 mg/kg Remodelin , i.p.injection

Applications

Remodelin significantly reduced AR-negative prostate cancer tumor growth, and in the high-dose Remodelin group, xenograft tumor weight at the endpoint was also much smaller than that in the low-dose group.Remodelin suppresses the growth and tumorigenesis potential of prostate cancer cells.

Remodelin is a small molecule inhibitor of N-acetyltransferase 10 (NAT10).Dysregulation of N-acetyltransferase 10 (NAT10) is associated with the development of many types of tumors^[1].

Combined remodelin and doxorubicin treatment reduced cell viability significantly more compared to cells treated with doxorubicin alone. EDU assays confirmed that both doxorubicin and remodelin decreased breast cancer cell proliferation more compared to cells treated with doxorubicin alone, suggesting remodelin attenuates doxorubicin resistance in breast cancer cells (MDA-MB-231)^[2]

Remodelin was given daily by intragastric administration for 4 weeks. PDX model tumour volume was recorded and TGI was calculated. As a result, Remodelin significantly inhibited the growth of HNSCC PDXs in vivo^[3]

The treatment of Remodelin could suppress the growth of cancer cells but not induce apoptosis, that Remodelin has little cytotoxicity. Remodelin significantly reduced AR-negative prostate cancer tumor growth. The anti-neoplastic effects of Remodelin through NAT10 inhibition should be credited to the slowing down of DNA replication, which could consequently attenuate replication stress-associated genomic instability, and ultimately delay the progression of prostate cancer^[4]

References:
[1]. Ma R, Chen J, et al. Up regulation of NAT10 promotes metastasis of hepatocellular carcinoma cells through epithelial-to-mesenchymal transition.
[2]. Wu J, Zhu H, et al. Inhibition of N-acetyltransferase 10 using remodelin attenuates doxorubicin resistance by reversing the epithelial-mesenchymal transition in breast cancer. Am J Transl Res. 2018 Jan 15;10(1):256-264.
[3]. Tao W, Tian G, et al. NAT10 as a potential prognostic biomarker and therapeutic target for HNSCC. Cancer Cell Int. 2021 Aug 6;21(1):413.
[4]. Ma N, Liu H, et al.Inhibition of N-Acetyltransferase 10 Suppresses the Progression of Prostate Cancer through Regulation of DNA Replication. Int J Mol Sci. 2022 Jun 12;23(12):6573.