# Intracellular Delivery of a p21-Derived Cell Cycle Inhibitory Peptide Using Elastin-like Polypeptides Suppresses Glioblastoma Cell Proliferation

**Authors:** Tiffany Quinn, Yumnaa Shaheen, Drazen Raucher

PMC · DOI: 10.3390/molecules31040597 · 2026-02-09

## TL;DR

A new delivery method using a p21-derived peptide suppresses the growth of glioblastoma cells without causing significant cell death.

## Contribution

A novel delivery system using elastin-like polypeptides to deliver a p21-derived peptide is shown to inhibit glioblastoma cell proliferation.

## Key findings

- The p21-ELP1-Bac treatment inhibited proliferation in three glioblastoma cell lines.
- U87 cells were most sensitive, while GBM6 cells showed the greatest drug tolerance.
- Confocal microscopy showed the peptide was internalized and localized near the nucleus.

## Abstract

Glioblastoma, with a 5-year survival rate of just under 7.0%, is the most common form of brain cancer in adults. In this study, we evaluated the antiproliferative activity of the biopolymer p21-ELP1-Bac, a p21-derived peptide delivered via an elastin-like polypeptide (ELP1) carrier and a cell-penetrating peptide (CPP), across three glioblastoma cell lines: U87, GBM43, and GBM6. We assessed proliferation, cell cycle progression, and apoptosis to determine whether ELP-mediated intracellular delivery of p21-ELP1-Bac suppresses glioblastoma growth through cytostatic mechanisms rather than inducing apoptosis. Treatment with the modified protein effectively inhibited proliferation across all three lines, with U87 cells showing the greatest sensitivity and GBM6 cells demonstrating the greatest drug tolerance. Although apoptotic responses were generally low, they appeared more pronounced in GBM6 cells. Confocal microscopy revealed sustained cellular uptake and signal observed in both the cytoplasm and in proximity to the nucleus in all cell lines. Collectively, these findings indicate that p21-ELP1-Bac is efficiently internalized and capable of modulating proliferation across all three glioblastoma cell lines, supporting its further evaluation as a cytostatic delivery platform.

## Linked entities

- **Genes:** CDKN1A (cyclin dependent kinase inhibitor 1A) [NCBI Gene 1026]
- **Diseases:** glioblastoma (MONDO:0018177)

## Full-text entities

- **Genes:** H3P16 (H3 histone pseudogene 16) [NCBI Gene 644914] {aka H3.6, H3F3AP6, p21}, Cdkn1a (cyclin dependent kinase inhibitor 1A) [NCBI Gene 12575] {aka CAP20, CDKI, CIP1, Cdkn1, P21, SDI1}, Epb41 (erythrocyte membrane protein band 4.1) [NCBI Gene 269587] {aka 4.1R, D4Ertd442e, Elp-1, Elp1, Epb4.1, mKIAA4056}, ELP1 (elongator acetyltransferase complex subunit 1) [NCBI Gene 8518] {aka DYS, FD, IKAP, IKBKAP, IKI3, TOT1}, CDKN1A (cyclin dependent kinase inhibitor 1A) [NCBI Gene 1026] {aka CAP20, CDKN1, CIP1, MDA-6, P21, SDI1}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, NR5A1 (nuclear receptor subfamily 5 group A member 1) [NCBI Gene 2516] {aka AD4BP, ELP, FTZ1, FTZF1, POF7, SF-1}, ANXA5 (annexin A5) [NCBI Gene 308] {aka ANX5, CPB-I, ENX2, HEL-S-7, PP4, RPRGL3}, CDK2 (cyclin dependent kinase 2) [NCBI Gene 1017] {aka CDKN2, p33(CDK2)}, RNASE1 (ribonuclease A family member 1, pancreatic) [NCBI Gene 6035] {aka RAC1, RIB1, RNS1}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}
- **Diseases:** GBM (MESH:D005909), brain cancer (MESH:D001932), necrosis (MESH:D009336), ovarian cancer (MESH:D010051), cytotoxic (MESH:D064420), IV malignancy (MESH:D009369), injury to (MESH:D014947), prostate cancer (MESH:D011471), intracranial glioma tumors (MESH:D005910)
- **Chemicals:** PBS (MESH:D007854), Sytox Green (MESH:C402795), TRITC (MESH:C009434), CO2 (MESH:D002245), CPP (MESH:D057846), Etoposide (MESH:D005047), amino acid (MESH:D000596), doxorubicin (MESH:D004317), penicillin (MESH:D010406), Bac (-), PI (MESH:D011419), ethanol (MESH:D000431), Polypeptide (MESH:D010455), streptomycin (MESH:D013307), Rhodamine (MESH:D012235), methanol (MESH:D000432)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** U87 — Homo sapiens (Human), Glioblastoma, Cancer cell line (CVCL_0022), GBM43 — Homo sapiens (Human), Glioblastoma, Cancer cell line (CVCL_DG57), GBM6 — Homo sapiens (Human), Glioblastoma, Cancer cell line (CVCL_DG62)

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12943708/full.md

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Source: https://tomesphere.com/paper/PMC12943708