Targeting colorectal cancer cell metabolism through development of cisplatin and metformin nano-cubosomes

Abstract

Drug-loaded nano-cubosomes ensued depletion in glucose and energy levels that led to AMPK activation and thus mTOR inhibition. mTOR was additionally inhibited via suppression of p-Akt (Ser473) levels after nano-cubosomal treatment. [...]drug-loaded nano-cubosomes produced a notable escalation in ROS levels, evident as an increase in NADPH oxidase, inhibition of LDH and a consequential upsurge in caspase-3. The statistical significance of the results was analyzed using one way ANOVA followed by Tukey-Kramer multiple comparison test. aSignificantly different from control, bfrom metformin cfrom cisplatin dfrom cisplatin nano-cubosomes e from cisplatin-metformin nano-cubosomes (P < 0.05) Increased AMP/ATP ratio in treated cells Figure 5c shows an increase in AMP/ATP ratio marking an increase in ATP consumption or decreased synthesis. [...]the prepared cisplatin and cisplatin-metformin nano-cubosomes could be potent agents in CRC treatment for further evaluation. Authors’ Affiliations (1) Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini St, Cairo, 11562, Egypt (2) Institute of Molecular Medicine I, Medical Faculty, Heinrich-Heine-University, Universitätsstr. 1, Building 23.12, 40225 Düsseldorf, Germany (3) Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini St, Cairo, 11562, Egypt (4) Pharmacology Unit, Department of Cancer Biology, National Cancer Institute, Cairo University, Kasr El-Aini St., Fom El Khalig, Cairo, 11796, Egypt Milczarek M, Rosinska S, Psurski M, Maciejewska M, Kutner A, Wietrzyk J. Combined colonic cancer treatment with vitamin D analogs and irinotecan or oxaliplatin.