Chondroitin sulfate as a molecular portal that preferentially mediates the apoptotic killing of tumor cells by penetratin-directed mitochondria-disrupting peptides.

Yang H, Liu S, Cai H, Wan L, Li S, Li Y, Cheng J, Lu X

The Journal of biological chemistry18 May 2010Cited by 32 (Europe PMC)

PMID20484051PMCIDPMC2919130DOI10.1074/jbc.m109.089417PepBankPUB-20484051

Summary

The use of cell-penetrating peptides (CPPs) as drug carriers for targeted therapy is limited by the unrestricted cellular translocation of CPPs. The preferential induction of tumor cell death by penetratin (Antp)-directed peptides (PNC27 and PNC28), however, suggests that the CPP Antp may contribute to the preferential cytotoxicity of these peptides. Using PNC27 as a molecular model, we constructed three novel peptides (PT, PR9, and PD3) by replacing the leader peptide Antp with one of three distinct CPPs (TAT, R9, or DPV3), respectively. The IC(50) values of PNC27 in tumor cells were 2-3 times lower than in normal cells. However, all three engineered peptides demonstrated similar cytotoxic effects in tumor and normal cells. Another three chimeric peptides containing the leader peptide Antp with different mitochondria-disrupting peptides (KLA-Antp (KGA), B27-Antp (BA27), and B28-Antp (BA28)), preferentially induced apoptosis in tumor cells. The IC(50) values of these peptides (3-10 microM) were 3-6 times lower in tumor cells than in normal cells. In contrast, TAT-directed peptides (TAT-KLA (TK), TAT-B27 (TB27), and TAT-B28 (TB28)), were cytotoxic to both tumor and normal cells. These data demonstrate that the leader peptide Antp contributes to the preferential cytotoxicity of Antp-directed peptides. Furthermore, Antp-directed peptides bind chondroitin sulfate (CS), and the removal of endogenous CS reduces the cytotoxic effects of Antp-directed peptides in tumor cells. The overexpression of CS in tumor cells is positively correlated to the cell entry and cytotoxicity of Antp- directed peptides. These results suggest that CS overexpression in tumor cells is an important molecular portal that mediates the preferential cytotoxicity of Antp-directed peptides.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

1 result from studies that gave the peptide. No result from this study comes from people.

01LabIn vitro (cells)Activity measurement
In cell tests, PNC27 IC50 values were lower in tumor cells than normal cells.
In plain wordsIn cells, PNC27 needed lower concentrations to kill tumor cells than normal cells.
Peptide
PNC-27
Outcome
DecreaseCytotoxic IC50
Study
n: not reported in source
Comparator
Normal cells
Outcome group
Tumor growth · Cancer
Studied dose
Dose not stated
Measurements
IC50 reduction factor
2 to 3 fold
tumor cells relative to normal cells
Source sentences
Summary
The IC(50) values of PNC27 in tumor cells were 2-3 times lower than in normal cells.
Show in the study text Report a problemFND-2048405101

Studies that did not test the peptide alone4

In this study, PNC-27 was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking PNC-27.

02LabNot a test of PNC-27 aloneIn vitro (cells)Mechanism
In cell studies, Antp-directed peptides, the class containing PNC27, bound chondroitin sulfate.
In plain wordsIn cells, Antp-directed peptides, including the PNC27 class, bound chondroitin sulfate.
Peptide
PNC-27
Outcome
Not applicableChondroitin sulfate binding
Study
n: not reported in source
Outcome group
Receptor activity and mechanism · Cancer
Source sentences
Summary
Furthermore, Antp-directed peptides bind chondroitin sulfate (CS),
1 context sentence(design, population, supporting numbers)
Summary · context
The preferential induction of tumor cell death by penetratin (Antp)-directed peptides (PNC27 and PNC28), however, suggests that the CPP Antp may contribute to the preferential cytotoxicity of these peptides.
In this study, PNC-27 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking PNC-27.
Show in the study text Report a problemFND-2048405102
03LabNot a test of PNC-27 aloneIn vitro (cells)Activity measurement
In tumor cells, endogenous chondroitin sulfate removal reduced cytotoxicity of Antp-directed peptides, the class containing PNC27.
In plain wordsIn cells, removal of natural chondroitin sulfate reduced tumor killing by Antp-directed peptides, the class containing PNC27.
Peptide
PNC-27
Outcome
DecreaseCytotoxicity after chondroitin sulfate removal
Study
n: not reported in source
Outcome group
Tumor growth · Cancer
Source sentences
Summary
the removal of endogenous CS reduces the cytotoxic effects of Antp-directed peptides in tumor cells.
1 context sentence(design, population, supporting numbers)
Summary · context
The preferential induction of tumor cell death by penetratin (Antp)-directed peptides (PNC27 and PNC28), however, suggests that the CPP Antp may contribute to the preferential cytotoxicity of these peptides.
In this study, PNC-27 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking PNC-27.
Show in the study text Report a problemFND-2048405103
04LabNot a test of PNC-27 aloneIn vitro (cells)Mechanism
In tumor cells, chondroitin sulfate overexpression correlated positively with entry of Antp-directed peptides, the class containing PNC27.
In plain wordsIn cells, higher chondroitin sulfate expression was linked to more entry of Antp-directed peptides, the class containing PNC27.
Peptide
PNC-27
Outcome
IncreaseCell entry association with chondroitin sulfate expression
Study
n: not reported in source
Outcome group
Receptor activity and mechanism · Cancer
Source sentences
Summary
The overexpression of CS in tumor cells is positively correlated to the cell entry and cytotoxicity of Antp- directed peptides.
1 context sentence(design, population, supporting numbers)
Summary · context
The preferential induction of tumor cell death by penetratin (Antp)-directed peptides (PNC27 and PNC28), however, suggests that the CPP Antp may contribute to the preferential cytotoxicity of these peptides.
In this study, PNC-27 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking PNC-27.
Show in the study text Report a problemFND-2048405104
05LabNot a test of PNC-27 aloneIn vitro (cells)Activity measurement
In tumor cells, chondroitin sulfate overexpression correlated positively with cytotoxicity of Antp-directed peptides, the class containing PNC27.
In plain wordsIn cells, higher chondroitin sulfate expression was linked to more killing by Antp-directed peptides, the class containing PNC27.
Peptide
PNC-27
Outcome
IncreaseCytotoxicity association with chondroitin sulfate expression
Study
n: not reported in source
Outcome group
Tumor growth · Cancer
Source sentences
Summary
The overexpression of CS in tumor cells is positively correlated to the cell entry and cytotoxicity of Antp- directed peptides.
1 context sentence(design, population, supporting numbers)
Summary · context
The preferential induction of tumor cell death by penetratin (Antp)-directed peptides (PNC27 and PNC28), however, suggests that the CPP Antp may contribute to the preferential cytotoxicity of these peptides.
In this study, PNC-27 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking PNC-27.
Show in the study text Report a problemFND-2048405105

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
21 Oct 2026, 12:50 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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