Journal: medRxiv

Article Title: FIS103, a Novel SULT1A1-dependent Prodrug, Demonstrates Potent Antitumor Activity in Renal Cell Carcinoma

doi: 10.1101/2024.03.21.24304257

Figure Lengend Snippet:

Article Snippet: The membrane was incubated with SULT1A1 primary antibody (R&D Systems, Cat no: MAB5546) diluted in blocking buffer overnight at 4°C.

Techniques: Expressing

Journal: medRxiv

Article Title: FIS103, a Novel SULT1A1-dependent Prodrug, Demonstrates Potent Antitumor Activity in Renal Cell Carcinoma

doi: 10.1101/2024.03.21.24304257

Figure Lengend Snippet: A) Kaplan-Meier Plots indicating that high expression of SULT1A1 mRNA correlates with poor prognosis for patients with i) kidney renal clear cell carcinoma, ii) brain lower grade glioma, and iii) uveal melanoma. Percentage of patients with B) high SULT1A1 mRNA expression in RCC subtypes (RNASeq from the TCGA PanCancer study), and C) with SULT1A1 mutation (whole genome sequencing from the TCGA PanCancer study and Genentech 2014 study). All TCGA data was extracted via cBioPortal. The number of cases per RCC subtypes is as followed: clear cell RCC (ccRCC) n=512, papillary RCC (pRCC) n=283, chromophobe RCC (chrRCC) n=65, non-clear cell RCC (nccRCC) n=146.

Article Snippet: The membrane was incubated with SULT1A1 primary antibody (R&D Systems, Cat no: MAB5546) diluted in blocking buffer overnight at 4°C.

Techniques: Expressing, Mutagenesis, Sequencing

Journal: medRxiv

Article Title: FIS103, a Novel SULT1A1-dependent Prodrug, Demonstrates Potent Antitumor Activity in Renal Cell Carcinoma

doi: 10.1101/2024.03.21.24304257

Figure Lengend Snippet: A) SULT1A1 mRNA levels in SULT1A1 positive (T47D) and SULT1A1 negative (MDA-MB-231) cell lines. B) FIS03 demonstrated differential cell killing (cell viability assay) in T47D but not MDA-MB-231 cells, showing SULT1A1 dependency. C) The differential cytotoxic effect of FIS103 was dose dependent (concentration is nM). DMSO was used as vehicle control.

Article Snippet: The membrane was incubated with SULT1A1 primary antibody (R&D Systems, Cat no: MAB5546) diluted in blocking buffer overnight at 4°C.

Techniques: Viability Assay, Concentration Assay, Control

Journal: medRxiv

Article Title: FIS103, a Novel SULT1A1-dependent Prodrug, Demonstrates Potent Antitumor Activity in Renal Cell Carcinoma

doi: 10.1101/2024.03.21.24304257

Figure Lengend Snippet: A) Proposed mechanism of action of N-BIC compounds after activation by SULT1A1 enzyme. B) Aligned and superimposed representative structures of SULT1A1: 1LS6 (green) and 2D06 (grey). C) Cluster representative structure of FIS103 during 100ns MD simulation with i) 2D06 and ii) ILS6.

Article Snippet: The membrane was incubated with SULT1A1 primary antibody (R&D Systems, Cat no: MAB5546) diluted in blocking buffer overnight at 4°C.

Techniques: Activation Assay

Journal: medRxiv

Article Title: FIS103, a Novel SULT1A1-dependent Prodrug, Demonstrates Potent Antitumor Activity in Renal Cell Carcinoma

doi: 10.1101/2024.03.21.24304257

Figure Lengend Snippet: A) SULT1A1 mRNA and protein expression in RCC SULT1A1 high- and SULT1A1 low-expressing cell lines. B) Cell viability assay demonstrating FIS103 treatment in SULT1A1 high-expression RCC cells. C) Cell viability assay demonstrating lack of toxicity of FIS103 up to 1 uM on cells with low SULT1A1 expression. D) Cell viability assay demonstrating lack of toxicity of FIS103 versus the parental compound (NSC-743380) in SULT1A1 non-expressing cells (MDA-MB-231). E) 6-week old NU/J mice were injected with 10 6 A498 cells to allow tumor growth for 20 days before intraperitoneal injection of FIS103 at indicated concentrations for 14 days (once daily). Test groups for mice (table) and relative weights by treatment group (blue, vehicle; orange, 25 mg/kg; grey, 50 mg/kg then 10 mg/kg) over the course of the 41-day study. F) Tumor volume was measured over the course of the study (left). Control group tumors grew for 20 days and were then sacrificed due to excess tumor burden. Treatment groups were started at 24 mg/kg and 50 mg/kg doses. Mice getting 50 mg/kg showed signs of toxicity, and 2 died. The rest of this group were given a 3 day drug holiday and then treated at 10 mg/kg. All mice in the treatment groups had tumors that became non-detectable after 14 days and remained absent through study conclusion. Representative photos of the mice in each group are shown (right).

Article Snippet: The membrane was incubated with SULT1A1 primary antibody (R&D Systems, Cat no: MAB5546) diluted in blocking buffer overnight at 4°C.

Techniques: Expressing, Viability Assay, Injection, Control

Journal: Frontiers in Chemistry

Article Title: Next-generation of BBQ analogues that selectively target breast cancer

doi: 10.3389/fchem.2024.1396105

Figure Lengend Snippet: Analysis of (A) AhR, (B) CYP1A1, (C) CYP1B1 and (D) SULT1A1 gene expression (fold-increase in mRNA compared with DMSO control) in MDA-MB-468 cells after 6 h exposure to compound 3 (0.2 μM = GI 50 , 1 μM) and FICZ (1 μM) and compound 5 (0.02 μM = GI 50 , 1 μM). * = p < 0.01 difference from DMSO control, using a paired T-test with a two-tailed distribution.

Article Snippet: The primer sequences were purchased from Qiagen as follows: AhR (QT02422938), CYP1A1 (QT00012341), CYP1B1 (QT00209496), SULT1A1 (QT01665489), and β2M (QT00088935).

Techniques: Expressing, Control, Two Tailed Test

Journal: Frontiers in Chemistry

Article Title: Next-generation of BBQ analogues that selectively target breast cancer

doi: 10.3389/fchem.2024.1396105

Figure Lengend Snippet: CYP1 and SULT1A1 inhibition ameliorates the effect of 5 . Growth inhibition (72 h, MTT assay) of 5 in the presence of the (A) CYP1 family inhibitor, α-naphthoflavone (αNF, 10 μM) and (B) SULT1A1 inhibitor, quercetin (5 μM), in MDA-MB-468 breast cancer cells. Significant differences between growth inhibition of compound 5 with (green) and without inhibitors (blue) is shown at the p < 0.01 ** and p < 0.05 * level, using a paired T-test with a two-tailed distribution. The effect of αNF and quercetin at the single concentration of 10µM and 5 µM respectively is shown in red as a single value.

Article Snippet: The primer sequences were purchased from Qiagen as follows: AhR (QT02422938), CYP1A1 (QT00012341), CYP1B1 (QT00209496), SULT1A1 (QT01665489), and β2M (QT00088935).

Techniques: Inhibition, MTT Assay, Two Tailed Test, Concentration Assay

Journal: Current Research in Toxicology

Article Title: Acceleration of benzo(a)pyrene-induced colon carcinogenesis by Western diet in a rat model of colon cancer

doi: 10.1016/j.crtox.2024.100162

Figure Lengend Snippet: A. SULT1A1 protein expression in liver samples of PIRC rats following treatment with B(a)P and consumption of RD or WD. b. GST protein expression in liver samples of PIRC rats. Annotations denote statistical significance ( ± p < 0.001, t p < 0.0001, ≠ p < 0.05 compared to RD Only, + p < 0.01 compared to RD Only, Φ p < 0.0001 compared to RD Only, Ø p < 0.05 compared to WD Only, and ∼ p < 0.0001 compared to WD Only) among diets and B(a)P concentrations used.

Article Snippet: The CYP1A1, CYP1B1, GST, SULT1A1 and GAPDH antibodies were purchased from Santa Cruz Biotechnology (Santa Cruz, CA).

Techniques: Expressing

Journal: Current Research in Toxicology

Article Title: Acceleration of benzo(a)pyrene-induced colon carcinogenesis by Western diet in a rat model of colon cancer

doi: 10.1016/j.crtox.2024.100162

Figure Lengend Snippet: A. SULT1A1 protein expression in colon samples of PIRC rats following treatment with B(a)P and consumption of RD or WD. Annotations denote statistical significance ( x p < 0.01, and Φ p < 0.0001 compared to RD Only, and ∼ p < 0.0001 compared to WD Only) among diets and B(a)P doses used. B. GST protein expression in colon samples of PIRC rats following treatment with B(a)P and consumption of RD or WD. Annotations denote statistical significance ( x p < 0.01 and Ø p < 0.05 compared to Western Diet Only) among diets and B(a)P doses used.

Article Snippet: The CYP1A1, CYP1B1, GST, SULT1A1 and GAPDH antibodies were purchased from Santa Cruz Biotechnology (Santa Cruz, CA).

Techniques: Expressing, Western Blot