Cytotoxic and chemosensitizing effects of glycoalkaloidic extract on 2D and 3D models using RT4 and patient derived xenografts bladder cancer cells

Author(s)

Miranda, Mariza Abreu ^[1] ; Marcato, Priscyla Daniely ^[2] ; Mondal, Arindam ^[1] ; Chowdhury, Nusrat ^[1] ; Gebeyehu, Aragaw ^[1] ; Surapaneni, Sunil Kumar ^[1] ; Lopes Badra Bentley, Maria Vitoria ^[2] ; Amaral, Robson ^[3] ; Pan, Chong-Xian ^[3] ; Singh, Mandip ^[1]

Affiliation

^[1] Florida A&M Univ, Coll Pharm & Pharmaceut Sci, Tallahassee, FL 32307 - USA

^[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Ave Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[3] Univ Calif Davis, Dept Internal Med, Sacramento, CA 95817 - USA

• Document type: Journal article
• Source: Materials Science & Engineering C-Materials for Biological Applications; v. 119, FEB 2021.
• Web of Science Citations: 1

Abstract

Glycoalkaloids have been widely demonstrated as potential anticancer agents. However, the chemosensitizing effect of these compounds with traditional chemotherapeutic agents has not been explored yet. In a quest for novel effective therapies to treat bladder cancer (BC), we evaluated the chemosensitizing potential of glycoalkaloidic extract (GE) with cisplatin (cDDP) in RT4 and PDX cells using 2D and 3D cell culture models. Additionally, we also investigated the underlying molecular mechanism behind this effect in RT4 cells. Herein, we observed that PDX cells were highly resistant to cisplatin when compared to RT4 cells. IC50 values showed at least 2.16-folds and 1.4-folds higher in 3D cultures when compared to 2D monolayers in RT4 cells and PDX cells, respectively. GE + cDDP inhibited colony formation (40%) and migration (28.38%) and induced apoptosis (57%) in RT4 cells. Combination therapy induced apoptosis by down-regulating the expression of Bcl-2 (p < 0.001), Bcl-xL (p < 0.001) and survivin (p < 0.01), and activating the caspase cascade in RT4 cells. Moreover, decreased expression of MMP-2 and 9 (p < 0.01) were observed with combination therapy, implying its effect on cell invasion/migration. Furthermore, we used 3D bioprinting to grow RT4 spheroids using sodium alginate-gelatin as a bioink and evaluated the effect of GE + cDDP on this system. Cell viability assay showed the chemosensitizing effect of GE with cDDP on bio-printed spheroids. In summary, we showed the cytotoxicity effect of GE on BC cells and also demonstrated that GE could sensitize BC cells to chemotherapy. (AU)

• FAPESP's process: 17/09025-7 - Investigating the mechanism of action of Solanum lycocarpum glycoalkaloids free and encapsulated in nanoparticles: in vitro study and 3D cells platforms of bladder cancer and other cancer cells lines
• Grantee: Mariza Abreu Miranda
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor