Selective induction of intrinsic apoptosis in retinoblastoma cells by novel cationic antimicrobial dodecapeptides

Host defense peptides represent an important component of innate immunity. In this work, we report the anticancer properties of a panel of hyper-charged wholly cationic antimicrobial dodecapeptides (CAPs) containing multiple canonical forms of lysine and arginine residues. These CAPs displayed excel...

Full description

Saved in:
Bibliographic Details
Main Authors: Babu, Vishnu Suresh, Kizhakeyil, Atish, Dudeja, Gagan, Chaurasia, Shyam S., Barathi, Veluchami Amutha, Heymans, Stephane, Verma, Navin Kumar, Lakshminarayanan, Rajamani, Ghosh, Arkasubhra
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2023
Subjects:
Online Access:https://hdl.handle.net/10356/168796
Tags: Add Tag
No Tags, Be the first to tag this record!
Institution: Nanyang Technological University
Language: English
id sg-ntu-dr.10356-168796
record_format dspace
spelling sg-ntu-dr.10356-1687962023-06-25T15:37:32Z Selective induction of intrinsic apoptosis in retinoblastoma cells by novel cationic antimicrobial dodecapeptides Babu, Vishnu Suresh Kizhakeyil, Atish Dudeja, Gagan Chaurasia, Shyam S. Barathi, Veluchami Amutha Heymans, Stephane Verma, Navin Kumar Lakshminarayanan, Rajamani Ghosh, Arkasubhra Lee Kong Chian School of Medicine (LKCMedicine) Singapore Eye Research Institute Science::Medicine DNA Damage Antimicrobial Peptides Host defense peptides represent an important component of innate immunity. In this work, we report the anticancer properties of a panel of hyper-charged wholly cationic antimicrobial dodecapeptides (CAPs) containing multiple canonical forms of lysine and arginine residues. These CAPs displayed excellent bactericidal activities against a broad range of pathogenic bacteria by dissipating the cytoplasmic membrane potential. Specifically, we identified two CAPs, named HC3 and HC5, that effectively killed a significant number of retinoblastoma (WERI-Rb1) cells (p ≤ 0.01). These two CAPs caused the shrinkage of WERI-Rb1 tumor spheroids (p ≤ 0.01), induced intrinsic apoptosis in WERI-Rb1 cells via activation of caspase 9 and caspase 3, cleaved the PARP protein, and triggered off the phosphorylation of p53 and γH2A.X. Combining HC3 or HC5 with the standard chemotherapeutic drug topotecan showed synergistic anti-cancer activities. Overall, these results suggest that HC3 and HC5 can be exploited as potential therapeutic agents in retinoblastoma as monotherapy or as adjunctive therapy to enhance the effectiveness of currently used treatment modalities. Ministry of Education (MOE) Ministry of Health (MOH) Nanyang Technological University National Medical Research Council (NMRC) National Research Foundation (NRF) Published version NKV acknowledges funding support, in part, from the Singapore Ministry of Education (MOE) under its MOE Academic Research Fund (AcRF) Tier 1 Grant (2020-T1-001-062), and the National Research Foundation Singapore under its Open Fund Large Collaborative Grant (OFLCG18May-0028) and administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC). RL thanks funding support from the Singapore Ministry of Health’s National Medical Research Council under its Centre Grant Programme (MOH-001001-00) and Open Funding – Independent Research Grant (MOH-000963-00). The research internship of VSB in the NKV lab was supported by NKV’s Start-Up Grant, LKC Medicine, Nanyang Technological University Singapore (L0412290). 2023-06-19T07:08:56Z 2023-06-19T07:08:56Z 2022 Journal Article Babu, V. S., Kizhakeyil, A., Dudeja, G., Chaurasia, S. S., Barathi, V. A., Heymans, S., Verma, N. K., Lakshminarayanan, R. & Ghosh, A. (2022). Selective induction of intrinsic apoptosis in retinoblastoma cells by novel cationic antimicrobial dodecapeptides. Pharmaceutics, 14(11), 2507-. https://dx.doi.org/10.3390/pharmaceutics14112507 1999-4923 https://hdl.handle.net/10356/168796 10.3390/pharmaceutics14112507 36432697 2-s2.0-85149553766 11 14 2507 en MOE2020-T1-001-062 OFLCG18May-0028 MOH-001001-00 MOH-000963-00 L0412290 Pharmaceutics © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
DNA Damage
Antimicrobial Peptides
spellingShingle Science::Medicine
DNA Damage
Antimicrobial Peptides
Babu, Vishnu Suresh
Kizhakeyil, Atish
Dudeja, Gagan
Chaurasia, Shyam S.
Barathi, Veluchami Amutha
Heymans, Stephane
Verma, Navin Kumar
Lakshminarayanan, Rajamani
Ghosh, Arkasubhra
Selective induction of intrinsic apoptosis in retinoblastoma cells by novel cationic antimicrobial dodecapeptides
description Host defense peptides represent an important component of innate immunity. In this work, we report the anticancer properties of a panel of hyper-charged wholly cationic antimicrobial dodecapeptides (CAPs) containing multiple canonical forms of lysine and arginine residues. These CAPs displayed excellent bactericidal activities against a broad range of pathogenic bacteria by dissipating the cytoplasmic membrane potential. Specifically, we identified two CAPs, named HC3 and HC5, that effectively killed a significant number of retinoblastoma (WERI-Rb1) cells (p ≤ 0.01). These two CAPs caused the shrinkage of WERI-Rb1 tumor spheroids (p ≤ 0.01), induced intrinsic apoptosis in WERI-Rb1 cells via activation of caspase 9 and caspase 3, cleaved the PARP protein, and triggered off the phosphorylation of p53 and γH2A.X. Combining HC3 or HC5 with the standard chemotherapeutic drug topotecan showed synergistic anti-cancer activities. Overall, these results suggest that HC3 and HC5 can be exploited as potential therapeutic agents in retinoblastoma as monotherapy or as adjunctive therapy to enhance the effectiveness of currently used treatment modalities.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Babu, Vishnu Suresh
Kizhakeyil, Atish
Dudeja, Gagan
Chaurasia, Shyam S.
Barathi, Veluchami Amutha
Heymans, Stephane
Verma, Navin Kumar
Lakshminarayanan, Rajamani
Ghosh, Arkasubhra
format Article
author Babu, Vishnu Suresh
Kizhakeyil, Atish
Dudeja, Gagan
Chaurasia, Shyam S.
Barathi, Veluchami Amutha
Heymans, Stephane
Verma, Navin Kumar
Lakshminarayanan, Rajamani
Ghosh, Arkasubhra
author_sort Babu, Vishnu Suresh
title Selective induction of intrinsic apoptosis in retinoblastoma cells by novel cationic antimicrobial dodecapeptides
title_short Selective induction of intrinsic apoptosis in retinoblastoma cells by novel cationic antimicrobial dodecapeptides
title_full Selective induction of intrinsic apoptosis in retinoblastoma cells by novel cationic antimicrobial dodecapeptides
title_fullStr Selective induction of intrinsic apoptosis in retinoblastoma cells by novel cationic antimicrobial dodecapeptides
title_full_unstemmed Selective induction of intrinsic apoptosis in retinoblastoma cells by novel cationic antimicrobial dodecapeptides
title_sort selective induction of intrinsic apoptosis in retinoblastoma cells by novel cationic antimicrobial dodecapeptides
publishDate 2023
url https://hdl.handle.net/10356/168796
_version_ 1772826997091729408