Figure S1. Effect of quinacrine in endometrial cancer cell viability in vitro. Quinacrine exhibits cytotoxic effect against EC

cells as measured by decreased cellular viability using MTT assay and decreased colony formation ability using CFA

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assay. A and B: Percent cell viability of HEC-1b and ARK-2, respectively, after 48 hours of treatment with increasing

concentrations with QC. C and D: Surviving fraction of colonies after 24 hours of exposure to increasing concentrations

with QC.

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Figure S2. Quinacrine re-sensitizes endometrial cancer cell lines to cisplatin and paclitaxel. When cells were treated with

increasing concentrations of cisplatin or paclitaxel combined with a constant concentration of QC, there was a shift of the

cisplatin or paclitaxel IC50 towards lower concentrations in both HEC-1b and ARK-2. A and B: Cisplatin with QC in HEC-

1b and ARK-2, respectively. C and D: Paclitaxel with QC in HEC-1b and ARK-2, respectively.

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Figure S3. Treatment schema of the endometrial cancer subcutaneous xenograft model. Day 0 was considered the day

on which most of the mice had developed subcutaneous implants measuring 3 mm by 3 mm (approximately day 4 after

implantation). Treatment was initiated on day 3 (approximately 7 days post-implantation). There were 5 treatment groups

(N=8-10/group): Group 1. Control; Group 2. QC only: QC alone at 100 mg/kg via oral gavage every 48 hours for 3

weeks; Group 3. Chemotherapy only: Carboplatin/paclitaxel via intraperitoneal injection at 16 mg/kg and 20 mg/kg,

respectively on days 3, 7, and 11; Group 4. Combination: Carboplatin/paclitaxel at 16 mg/kg and 20 mg/kg, respectively,

on days 3, 7, and 11 plus QC at 100 mg/kg via oral gavage every 48 hours until day 11; and Group 5. Maintenance:

Carboplatin/paclitaxel at 16 mg/kg and 20 mg/kg, respectively, on days 3, 7, and 11 plus QC at 100 mg/kg via oral gavage

every 48 hours until the end of the study.

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Figure S4. Extent of tumor necrosis in vivo in endometrial cancer mouse xenografts across treatment groups as

demonstrated in H&E staining. Percent tumor necrosis was calculated as surface of necrotic areas within the tumor over

the whole area of the tumor per slide and was expressed as a fraction of 100. A. Outlier box plots of the percent tumor

necrosis across treatment groups; the median (IQR), mean, outliers and the “shortest half” (the more dense 50% of the

observations as depicted by the red brackets) are graphed. *P<0.05: QC monotherapy vs. control (P=0.01), maintenance

vs. control (P=0.01) (Dunnett’s test). B. Table with the median and IQR of the percent tumor necrosis across treatment

groups. (N=8-10/group). C. Indicative H&E-stained slides from individual xenografts from each treatment group with

observed extent of tumor necrosis approximating each treatment group’s median percent tumor necrosis for comparison.

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Figure S5. Effect of treatment in vivo on tumor cell proliferation in endometrial cancer mouse xenografts as measured by

Ki-67 staining. The Ki-67 labeling index is the percentage of positively Ki-67 immunostained cellular areas out of the total

nuclear area that was calculated using a publicly available image analysis software called ImmunoRatio. A. Outlier box

plots of the Ki-67 labeling index across treatment groups; the median (IQR), mean, outliers and the “shortest half” (the

more dense 50% of the observations as depicted by the red brackets) are graphed. *P<0.01 (level of significance after

Bonferroni adjustment for a total of 5 comparisons): QC monotherapy vs. control P=0.002, carboplatin plus paclitaxel vs.

control P=0.002, combination treatment vs. control P=0.002, maintenance treatment vs. control P=0.002 (Dunnett’s test);

maintenance treatment vs. carboplatin plus paclitaxel #P<0.001 (Wilcoxon rank-sum test). B. Table with the median and

IQR of the Ki-67 labeling index across treatment groups. (N=8-10/group). C. Indicative Ki-67-stained slides from individual

xenografts from each treatment group with calculated Ki-67 labeling index approximating each treatment group’s median

for comparison.

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Figure S6. Effect of treatment in vivo on microvessel density in endometrial cancer mouse xenografts as measured by

CD31 staining. The intratumor Microvessel Density (iMVD) is expressed as the highest number of microvessels among 5

areas of invasive tumor representative of the highest microvessel density areas (neovascular "hot spots") for each

xenograft. A. Outlier box plots of the iMVD across treatment groups; the median (IQR), mean, outliers and the “shortest

half” (the more dense 50% of the observations as depicted by the red brackets) are graphed. *P<0.05: QC monotherapy

vs. control (P=0.02), combination vs. control (P=0.005), maintenance vs. control (P=0.008) (Dunnett’s test). B. Table with

the median and IQR of iMVD across treatment groups. (N=8-10/group). C. Indicative CD31-stained slides from individual

xenografts from each treatment group with iMVD approximating each treatment group’s median for comparison.

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