C A M A - 1 M D A - M B - 3 6 1 ( H E R 2 + ) H C C - 1 5 6 9 ( H E R 2 + ) B T 4 7 4 ( H E R 2 + ) H S 5 7 8 T M D A - M B - 4 1 5 ( L u m i n a l ) M D A - M B - 2 3 1 M D A - M B - 4 6 8 M D A - M B - 4 3 6 B T 2 0 T M D A - M B - 1 5 7 7 6 N 1 0 A 7 6 N F 2 V 7 6 N E 7 T 4 7 D Z R 7 5 - 1 M C F - 7 M D A - M B - 4 5 3 ( H E R 2 + ) H C C 3 8 M 4 A 4 N M 2 C 5 H C C - 1 5 0 0 H C C - 1 9 5 4 H C C - 1 4 2 8 H C C - 1 4 1 9 ( H E R 2 + ) H C C - 1 9 3 7 D U 4 4 7 5 H C C - 1 8 0 6 U A C C - 8 9 3 ( H E R 2 + ) A U 5 6 5 ( H E R 2 + ) S K B R 3 ( H E R 2 + ) U A C C 8 9 3 ( H E R 2 + ) B T 4 8 3 B T 5 4 9 Cyclin E Actin Cyclin E Actin Cyclin E Actin Densitometry Units Subtype LMW-E Levels A B p=0.003 Supplemental Figure 1 Full Length Cyclin E Levels
I3C Sensitive Cells p-valueNRF2-mediated Oxidative Stress Response 2.00E-10Cell Cycle: G2/M DNA Damage Checkpoint Regulation 2.14E-08Protein Ubiquitination Pathway 1.07E-07Role of BRCA1 in DNA Damage Response 3.55E-07Molecular Mechanisms of Cancer 1.20E-06PI3K/AKT Signaling 1.45E-06Role of CHK Proteins in Cell Cycle Checkpoint Control 1.78E-06p53 Signaling 2.40E-06Actin Nucleation by ARP-WASP Complex 5.75E-06Mitotic Roles of Polo-Like Kinase 1.00E-05ATM Signaling 1.00E-05Purine Metabolism 1.20E-05Aminoacyl-tRNA Biosynthesis 3.31E-05Breast Cancer Regulation by Stathmin1 3.55E-05Hereditary Breast Cancer Signaling 3.63E-05Fcγ Receptor-mediated Phagocytosis in Macrophages and Monocytes 3.98E-05Apoptosis Signaling 5.50E-05Inositol Phosphate Metabolism 6.03E-05Glioma Signaling 7.94E-05Rac Signaling 9.55E-05Pancreatic Adenocarcinoma Signaling 1.12E-04Aryl Hydrocarbon Receptor Signaling 1.23E-04Induction of Apoptosis by HIV1 1.29E-04Estrogen Receptor Signaling 1.35E-04Cell Cycle Control of Chromosomal Replication 1.78E-04
I3C Insensitive Cells p-valueNRF2-mediated Oxidative Stress Response 7.76E-0714-3-3-mediated Signaling 1.15E-05Valine, Leucine and Isoleucine Degradation 1.51E-05Integrin Signaling 2.95E-05Fcγ Receptor-mediated Phagocytosis in Macrophages and Monocytes 6.03E-05IL-8 Signaling 7.76E-05VEGF Signaling 9.77E-05One Carbon Pool by Folate 1.58E-04Virus Entry via Endocytic Pathways 1.95E-04Rac Signaling 2.24E-04Axonal Guidance Signaling 2.75E-04Actin Nucleation by ARP-WASP Complex 2.82E-04Role of Tissue Factor in Cancer 3.16E-04HER-2 Signaling in Breast Cancer 3.16E-04Actin Cytoskeleton Signaling 3.47E-04Signaling by Rho Family GTPases 3.55E-04Thrombin Signaling 4.17E-04Docosahexaenoic Acid (DHA) Signaling 4.57E-04Breast Cancer Regulation by Stathmin1 5.50E-04Glioma Signaling 5.50E-04Mechanisms of Viral Exit from Host Cells 6.46E-04Cell Cycle: G2/M DNA Damage Checkpoint Regulation 7.08E-04PI3K/AKT Signaling 7.41E-04Macropinocytosis Signaling 8.32E-04Germ Cell-Sertoli Cell Junction Signaling 1.07E-03
Supplemental Table 2
Supplemental Figure 2
IC50 (μM)
Control 490.8shAHR.1 585.0shAHR.2 570.0
MDA-MB-157
B
ControlshAHR.1shAHR.2
Actin
AhR
Control sh-AHR.1 sh-AHR.2
No
rma
lize
d A
bs
orb
an
ce
(5
90
nM
)
Log I3C concentration (μM)
D 100 250 D 100 250 D 100 250 μM
A
No
rma
lize
d A
bs
orb
an
ce
(5
90
nM
)
Log Tamoxifen concentration (μM)
A
No
rma
lize
d A
bs
orb
an
ce
(5
90
nM
)Log I3C concentration (μM)
B
ParentalTAM-R
IC50 (μM)
Parental 0.9TAM-R 5.2
IC50 (μM)
Parental 277.9TAM-R 253.1
Supplemental Figure 3
T47D
ZR75-1
MCF-7
MDA-MB-436
MDA-MB-231
MDA-MB-157
I3C (μM)
p53
Actin
- + - + - + - + I3C (250 μM)
Control sh1 sh2 sh3
MCF-7A B
p53
IC50 (μM)
Control 265.2shP53.1 254.2shP53.2 243.8shP53.3 222.3
