Sensitization of Cancer Cells via Non-Viral Delivery of Apoptosis Inducing Proteins Using a Cationic Bolaamphiphile.

Abstract

Cationic bolaamphiphile polymers had been previously studied as efficient delivery system for the delivery of proteins with relatively low toxicity. Here, the authors investigate the use of a protein delivery system based on a cationic bolaamphiphile to sensitize cancer cells toward apoptosis-inducing drugs as a novel approach for cancer therapy. The authors demonstrates the efficacy of the system by two strategies. The first strategy involves delivery of a survivin antibody to inhibit survivin activity. Sensitization of MCF-7 cells to doxorubicin is observed by survivin inhibition by antibodies. The IC50 of doxorubicin is reduced ≈2.5-fold after delivery of survivin antibodies to breast cancer cells and induction of apoptosis is shown by Western blotting with apoptosis specific antibodies. In a second approach, functional wild type p53 is delivered into p53-null liver cancer (Hep3B) cells, sensitizing the cells toward the p53 pathway drug, Nutlin. Nutlin reduced the viability of Hep3B cells by ≈42% at 15 μM concentration, demonstrating the effectiveness of p53 delivery. The expression of p21, a downstream target of p53 further confirmed the functional status of the delivered protein. In conclusion. The successful delivery of apoptosis inducing proteins and sensitization of cancer cells via cationic bolaamphiphile polymer represents a promising system for cancer therapeutics.

• Authors: Karthikeyan Narayanan, Majad Khan, Began Gopalan, Jane Antony, Tultul Das, Yi Yan Yang, Andrew C A Wan
• Journal: Biotechnology journal (Biotechnol J) Vol. 14 Issue 3 Pg. e1800020 (Mar 2019) ISSN: 1860-7314 [Electronic] Germany
• PMID: 29802765 (Publication Type: Journal Article)
• Copyright: © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Apoptosis Regulatory Proteins
• Cations
• Cyclin-Dependent Kinase Inhibitor p21
• Furans
• Pyridones
• Survivin
• Tumor Suppressor Protein p53
• bolaamphiphile
• Doxorubicin

Topics

• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (metabolism)
• Cations (pharmacology)
• Cell Line
• Cell Line, Tumor
• Cyclin-Dependent Kinase Inhibitor p21 (metabolism)
• Doxorubicin (pharmacology)
• Furans (pharmacology)
• Hep G2 Cells
• Humans
• Liver Neoplasms (metabolism)
• MCF-7 Cells
• Pyridones (pharmacology)
• Signal Transduction (drug effects)
• Survivin (metabolism)
• Tumor Suppressor Protein p53 (metabolism)