Enhanced anti-tumor activity of trichosanthin after combination with a human-derived cell-penetrating peptide, and a possible mechanism of activity

Lu, Ye-Zhou; Li, Pengfei; Li, Yanzhong; Luo, Fan; Guo, Chao; Lin, Bin; Cao, Xiaohong; Zhao, Jian; Wang, Fujun

doi:10.1016/j.fitote.2016.03.019

Cited by 11 publications

(9 citation statements)

References 28 publications

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“…In all of the tested CPPs, only HBP was a suitable candidate for improving the antitumor activity of α‐MMC significantly. These observations did not agree with those of results that HBD could enhance the intrinsic cytotoxicity of TCS or MAP30 . This phenomenon suggests that a mutual match between the cargo molecule and CPP would uniquely affect the various aspects of the biological activity of a recombinant protein.…”

Section: Discussioncontrasting

confidence: 64%

Effectively enhancing cytotoxic and apoptotic effects of alpha‐momorcharin by integrating a heparin‐binding peptide

Tan

Cao

et al. 2017

Biotech and App Biochem

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Alpha-momorcharin (α-MMC), a type I ribosome-inactivating protein, has attracted a great deal of attention because of its antitumor activity. However, the cytotoxicity of α-MMC is limited due to insufficient cellular internalization in cancer cells. To enhance the cytotoxicity of α-MMC, a heparin-binding domain derived from heparin-binding epidermal growth factor (named heparin-binding peptide [HBP]) was used as a cell-penetrating peptide and fused to the C-terminus of α-MMC. This novel α-MMC-HBP fusion protein was expressed and purified with a Ni -resin. The N-glycosidase activity and DNase activity assay indicated that the introduction of HBP did not interfere with the intrinsic bioactivities of α-MMC. HBP was able to efficiently carry α-MMC into the tested cancer cells and significantly enhance the cytotoxic effects of α-MMC in a dose-dependent manner. This enhanced cytotoxic ability occurred due to the higher level of cell apoptosis induced by α-MMC-HBP, which was demonstrated in western blot analysis in which α-MMC-HBP triggered caspase 8, caspase 9, casapase 3, and PARP more intensely than α-MMC alone. α-MMC-HBP led to an upregulation of cleaved PARP and an increase in the Bax/Bcl-2 ratio. Our study provided a new practical way to greatly improve the antitumor activity of α-MMC, which could significantly expand the pharmaceutical applications of α-MMC.

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Section: Discussioncontrasting

confidence: 64%

Effectively enhancing cytotoxic and apoptotic effects of alpha‐momorcharin by integrating a heparin‐binding peptide

Tan

Cao

et al. 2017

Biotech and App Biochem

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“…Nevertheless, the anticancer application of RIP has not yet been clinically realized due to its poor cellular uptake and inability to reach the ribosome . To overcome this limitation, researchers attempted to apply CPP as a means for RIP delivery into the cytoplasm to target and enzymatically destroy ribosome, ultimately leading to protein translation inhibition and cell death. − In 2013, Yang et al modified RIP-gelonin with CPP-LMWP using both chemical conjugates and genetic recombination that produced a gelonin-LMWP chemical conjugate (cG-L) and recombinant gelonin-LMWP chimera (rG-L), respectively. Both cG-L and rG-L efficiently entered cells and showed significantly increased tumoricidal effects over rGel.…”

Section: Cpp-based Organelle Functional Restorationmentioning

confidence: 99%

Emerging Landscape of Cell-Penetrating Peptide-Mediated Organelle Restoration and Replacement

Geng

Wang

2023

ACS Pharmacol. Transl. Sci.

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Organelles are specialized subunits within a cell membrane that perform specific roles or functions, and their dysfunction can lead to a variety of pathophysiologies including developmental defects, aging, and diseases (cancer, cardiovascular and neurodegenerative diseases). Recent studies have shown that cell-penetrating peptide (CPP)-based pharmacological therapies delivered to organelles or even directly resulting in organelle replacement can restore cell function and improve or prevent disease. In this review, we summarized the current developments in the precise delivery of exogenous cargoes via CPPs at the organelle level, CPP-mediated organelle delivery, and discuss their feasibility as next-generation targeting strategies for the diagnosis and treatment of diseases at the organelle level.

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“…The IC 50 of rTcs-HBD in the tested tumor cells was much lower than rTcs, showing that HBD delivered the rTcs into tumor cells efficiently. 149 Dual-modified nanocarriers with more than one ligand are gaining much attention in anticancer drug research. Chen et al developed bifunctional NPs (BF-NPs) based on PLGA-PEG and modified them with CPP (R 7 ) and folic acid simultaneously.…”

Section: Application Of Cpp/ttp Nanocarriers For Herb-based Anticancementioning

confidence: 99%

Tumor-targeting delivery of herb-based drugs with cell-penetrating/tumor-targeting peptide-modified nanocarriers

Kebebe¹,

Liu²,

Wu³

et al. 2018

IJN

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Cancer has become one of the leading causes of mortality globally. The major challenges of conventional cancer therapy are the failure of most chemotherapeutic agents to accumulate selectively in tumor cells and their severe systemic side effects. In the past three decades, a number of drug delivery approaches have been discovered to overwhelm the obstacles. Among these, nanocarriers have gained much attention for their excellent and efficient drug delivery systems to improve specific tissue/organ/cell targeting. In order to enhance targeting efficiency further and reduce limitations of nanocarriers, nanoparticle surfaces are functionalized with different ligands. Several kinds of ligand-modified nanomedicines have been reported. Cell-penetrating peptides (CPPs) are promising ligands, attracting the attention of researchers due to their efficiency to transport bioactive molecules intracellularly. However, their lack of specificity and in vivo degradation led to the development of newer types of CPP. Currently, activable CPP and tumor-targeting peptide (TTP)-modified nanocarriers have shown dramatically superior cellular specific uptake, cytotoxicity, and tumor growth inhibition. In this review, we discuss recent advances in tumor-targeting strategies using CPPs and their limitations in tumor delivery systems. Special emphasis is given to activable CPPs and TTPs. Finally, we address the application of CPPs and/or TTPs in the delivery of plant-derived chemotherapeutic agents.

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Enhanced anti-tumor activity of trichosanthin after combination with a human-derived cell-penetrating peptide, and a possible mechanism of activity

Cited by 11 publications

References 28 publications

Effectively enhancing cytotoxic and apoptotic effects of alpha‐momorcharin by integrating a heparin‐binding peptide

Effectively enhancing cytotoxic and apoptotic effects of alpha‐momorcharin by integrating a heparin‐binding peptide

Emerging Landscape of Cell-Penetrating Peptide-Mediated Organelle Restoration and Replacement

Tumor-targeting delivery of herb-based drugs with cell-penetrating/tumor-targeting peptide-modified nanocarriers

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