Pouya Haratipour

Second-Generation AOH1996 Analogues with Enhanced Pharmacological Properties for Targeting PCNA

Pouya Haratipour, Maryam Zangi, Long Gu, Caroline M. Li et autres

Abstract Proliferating Cell Nuclear Antigen (PCNA) plays a critical role in at least 11 distinct cellular pathways. Tumor cells express an acidic isoform of the protein (caPCNA), while nonmalignant cells express only a basic isoform (nmPCNA). We previously identified AOH1996 as a …

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Supplemental Figure 4 from Targeting Cancer-Associated PCNA with AOH1996 Induces Mitotic Catastrophe and Enhances Cisplatin Therapy in Cervical Cancer

Sebastian O. Wendel, Grant M. Brooke, Changkun Hu, Allison R. Sandoval et autres

Cisplatin pretreatment impairs AOH1996 efficacy by blocking mitotic entry in cervical cancer cells.

Supplemental Figure 5 from Targeting Cancer-Associated PCNA with AOH1996 Induces Mitotic Catastrophe and Enhances Cisplatin Therapy in Cervical Cancer

Sebastian O. Wendel, Grant M. Brooke, Changkun Hu, Allison R. Sandoval et autres

Xenograft Sizes, Study Arms and Treatment Regimen.

Supplemental Figure 6 from Targeting Cancer-Associated PCNA with AOH1996 Induces Mitotic Catastrophe and Enhances Cisplatin Therapy in Cervical Cancer

Sebastian O. Wendel, Grant M. Brooke, Changkun Hu, Allison R. Sandoval et autres

H&E Analysis Did Not Detect Gross Deferential Nephrotoxicity.

Figure 8 from Targeting Cancer-Associated PCNA with AOH1996 Induces Mitotic Catastrophe and Enhances Cisplatin Therapy in Cervical Cancer

Sebastian O. Wendel, Grant M. Brooke, Changkun Hu, Allison R. Sandoval et autres

AOH1996 synergizes with cisplatin in vivo and reduces cisplatin-associated toxicity. A, HeLa xenograft tumor volumes after monotherapy with mock treatment (black), cisplatin (blue), or AOH1996 (red). B, Corresponding mouse body weights. C, Kaplan–Meier survival analysis of mice treated with vehicle control, 8 …

Figure 7 from Targeting Cancer-Associated PCNA with AOH1996 Induces Mitotic Catastrophe and Enhances Cisplatin Therapy in Cervical Cancer

Sebastian O. Wendel, Grant M. Brooke, Changkun Hu, Allison R. Sandoval et autres

AOH1996 synergizes with cisplatin to enhance cytotoxicity in cervical cancer cells. A, Dose–response matrix of AOH1996 and cisplatin combinations in HFKs, HeLa, and CaSki cells measured by MTT viability assay. Heatmaps show normalized cell viability after 96 hours of treatment. Green indicates …

Figure 3 from Targeting Cancer-Associated PCNA with AOH1996 Induces Mitotic Catastrophe and Enhances Cisplatin Therapy in Cervical Cancer

Sebastian O. Wendel, Grant M. Brooke, Changkun Hu, Allison R. Sandoval et autres

AOH1996 induces mitotic arrest in cervical cancer (CaCx) cells. A, Cell-cycle analysis of HFKs and CaCx cell lines (HeLa, HeLa POLη, CaSki, and C33a) treated with 1 μmol/L AOH1996 for 24 or 48 hours. DNA content was measured by PI staining and …

Supplemental Figure 2 from Targeting Cancer-Associated PCNA with AOH1996 Induces Mitotic Catastrophe and Enhances Cisplatin Therapy in Cervical Cancer

Sebastian O. Wendel, Grant M. Brooke, Changkun Hu, Allison R. Sandoval et autres

AOH1996 induces abnormal nuclear morphology resulting in cell death in cervical cancer cells.

Figure 6 from Targeting Cancer-Associated PCNA with AOH1996 Induces Mitotic Catastrophe and Enhances Cisplatin Therapy in Cervical Cancer

Sebastian O. Wendel, Grant M. Brooke, Changkun Hu, Allison R. Sandoval et autres

AOH1996 binds to tubulin and disrupts PCNA–γ-tubulin interactions. A, Tubulin polymerization assay performed in vitro using purified tubulin. AOH1996 partially inhibits polymerization relative to DMSO and paclitaxel (positive control) but more effectively than the inert analog AOH1996-8Nq and the microtubule-depolymerizing agent colcemid …

Figure 5 from Targeting Cancer-Associated PCNA with AOH1996 Induces Mitotic Catastrophe and Enhances Cisplatin Therapy in Cervical Cancer

Sebastian O. Wendel, Grant M. Brooke, Changkun Hu, Allison R. Sandoval et autres

AOH1996 disrupts centrosome organization and spindle integrity. A, Representative immunofluorescence microscopy images of HFK, HeLa, and CaSki cells treated with DMSO or 1 μmol/L AOH1996 for 24 hours, stained for β-tubulin (red), γ-tubulin (green), and DNA (DAPI, blue). In DMSO-treated cells, mitotic …

Data from Targeting Cancer-Associated PCNA with AOH1996 Induces Mitotic Catastrophe and Enhances Cisplatin Therapy in Cervical Cancer

Sebastian O. Wendel, Grant M. Brooke, Changkun Hu, Allison R. Sandoval et autres

Abstract Cervical cancers remain a significant health burden. Limitations on cervical cancer chemotherapeutic intervention caused by toxic side effects are a persistent barrier to care. In this study, we show that the human papillomavirus oncogenes that cause most cervical cancers also increase …

Figure 2 from Targeting Cancer-Associated PCNA with AOH1996 Induces Mitotic Catastrophe and Enhances Cisplatin Therapy in Cervical Cancer

Sebastian O. Wendel, Grant M. Brooke, Changkun Hu, Allison R. Sandoval et autres

AOH1996 selectively induces apoptosis in cervical cancer (CaCx) cells. A, Dose–response curves of AOH1996 in primary HFKs, HeLa (HPV18+), CaSki (HPV16+), C33A (HPV−), and HeLa cells overexpressing POLη following 72 hours of treatment, assessed via MTT assay. HFKs show resistance, whereas all …