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

Tan, Meng-Jie; Cao, Xiaohong; Li, Pengfei; Zhai, Yi-Zhou; Zhou, Yu; Liu, Ye-Jun; Zhao, Jian; Wang, Fujun

doi:10.1002/bab.1553

Cited by 4 publications

(2 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, this region is also part of the heparin‐binding domain of BMP4. Previous studies by our group found that the heparin‐binding domains of many proteins are rich in basic amino acid residues, which can bind to extracellular heparin polysaccharides and quickly attach to the cell surface, which can be used as candidates for the development of highly efficient cell‐penetrating peptides (Li et al, 2020; Lu et al, 2016; Tan et al, 2017). Therefore, T3BP not only has the ability of target binding, but also has a good autonomous membrane penetration ability due to its rich basic amino acids.…”

Section: Discussionmentioning

confidence: 99%

Design and characterization of a novel tumor‐homing cell‐penetrating peptide for drug delivery in TGFBR3 high‐expressing tumors

Wu,

Lei,

Zhao

et al. 2023

Chem Biol Drug Des

Self Cite

View full text Add to dashboard Cite

Targeted therapy has attracted more and more attention in cancer treatment in recent years. However, due to the diversity of tumor types and the mutation of target sites on the tumor surface, some existing targets are no longer suitable for tumor therapy. In addition, the long‐term administration of a single targeted drug can also lead to drug resistance and attenuate drug potency, so it is important to develop new targets for tumor therapy. The expression of Type III transforming growth factor β receptor (TGFBR3) is upregulated in colon, breast, and prostate cancer cells, and plays an important role in the occurrence and development of these cancers, so TGFBR3 may be developed as a novel target for tumor therapy, but so far there is no report on this research. In this study, the structure of bone morphogenetic protein 4 (BMP4), one of the ligands of TGFBR3 was analyzed through the docking analysis with TGFBR3 and sequence charge characteristic analysis, and a functional tumor‐targeting penetrating peptide T3BP was identified. The results of fluorescent labeling experiments showed that T3BP could target and efficiently enter tumor cells with high expression of TGFBR3, especially A549 cells. When the expression of TGFBR3 on the surface of tumor cells (HeLa) was knocked down by RNA interference, the high delivery efficiency of T3BP was correspondingly reduced by 40%, indicating that the delivery was TGFBR3‐dependent. Trichosanthin (TCS, a plant‐derived ribosome inactivating protein) fused with T3BP can enhance the inhibitory activity of the fusion protein on A549 cells by more than 200 times that of TCS alone. These results indicated that T3BP, as a novel targeting peptide that can efficiently bind TGFBR3 and be used for targeted therapy of tumors with high expression of TGFBR3. This study enriches the supply of tumor‐targeting peptides and provides a new potential application option for the treatment of tumors with high expression of TGFBR3.

show abstract

Section: Discussionmentioning

confidence: 99%

Design and characterization of a novel tumor‐homing cell‐penetrating peptide for drug delivery in TGFBR3 high‐expressing tumors

Wu,

Lei,

Zhao

et al. 2023

Chem Biol Drug Des

Self Cite

View full text Add to dashboard Cite

show abstract

“…α-Momorcharin (α-MMC) is a ribosomal inactivation protein extracted from bitter melon seeds. It hydrolyzes the N-C glycoside bond between adenine base and ribosome at position A4324 of ribosomal 28SrRNA in eukaryotic cells, and prevents the binding of elongator EF-2 to ribosome, thereby inhibiting protein synthesis [3]. Studies have shown that α-MMC exerts immuneregulatory effects on breast carcinoma, colorectal carcinoma, hepatoma, non-small cell lung cancer, epithelial cell cancer and glioma [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Effect of α-momordicine on proliferation and apoptosis of liver cancer, and its associated mechanisms of action

Yang¹,

Wen²,

Shi³

et al. 2021

Trop. J. Pharm Res

View full text Add to dashboard Cite

Purpose: To investigate the effect of α-momordicine (α-MMC) on liver cancer cell proliferation and apoptosis, and to elucidate the mechanisms of action involved. Methods: In in vitro experiments, hepatoma cell lines were used, while nude mice with hepatocellular carcinoma were used for in vivo studies. Cancer cell proliferation was determined using MTT assay while apoptosis was assayed by flow cytometry and TUNNEL staining. Gene expression was determined with real-time polymerase chain reaction (RT-PCR), while protein expression levels were assayed by Western blot, immunohistochemistry and immunofluorescence. Results: Alpha-MMC decreased HCC cell viability dose-dependently (p < 0.05). In HepG2 cells, G2/M cell cycle was halted after 48 h intervention with 1.24 mg/mL α-MMC. However, at G0/G1 phase, αMMC at doses of 1.06 and 0.92 mg/mL caused cell cycle arrest of HCC-LM3 and SMMC-7721 cells. In vivo studies showed that after establishment of the nude mice liver cancer model, exposure to α-MMC at a dose of 0.70 mg/kg or 2.08mg/kg for 4 weeks reduced the size of liver cancer in the treatment group, relative to control group; mean diameter of liver cancer decreased from 2.16 to 0.51 cm, while mean volume decreased from 1.185 to 0.085 cm3 . Moreover, α-MMC increased apoptosis level in liver cancer tissues in nude mice, and down-regulated the expressions of P-AKT, RAGE, MMP-9 and HMGB1, but upregulated Bax/Bcl2 ratio (p < 0.05). Conclusion: α-MMC inhibits cancer cell growth and proliferation, and facilitates their apoptosis by positively regulating the ratio of Bax/Bcl2. The anti-liver cancer effect of α-MMC is mediated via HMGB1-RAGE and AKT signaling pathways

show abstract

Amidated Scolopin‐2 inhibits proliferation and induces apoptosis of Hela cells in vitro and in vivo

Yan

et al. 2018

Biotech and App Biochem

View full text Add to dashboard Cite

This study aimed to investigate the effect of Scolopin-2, a cationic antimicrobial peptide from centipede venoms, and amidated Scolopin-2 on Hela cell viability in vitro and in vivo. The cellular proliferation was investigated with the MTT assay. Confocal laser scanning, flow cytometry, and Western blot analysis were employed to localize Scolopin-2-NH in Hela cells and to study the caused cells apoptosis. We subcutaneously injected Hela cells into BALB/c nude mice and studied if Scolopin-2-NH suppressed tumor growth in the mice. Scolopin-2-NH inhibited Hela proliferation in vitro in a dose-dependent manner with an IC of 35 μM. In addition, Scolopin-2-NH combined with mitochondria and regulated caspase-related apoptosis pathways in Hela cells. Scolopin-2-NH significantly suppressed tumor growth in the tumor-bearing mice without side effects, such as weight loss or abnormal changes in tissues, including liver, spleen, kidney, and lung. These results indicate Scolopin-2-NH may be a good therapeutic candidate for the treatment of Hela cervical cancer.

show abstract

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

Cited by 4 publications

References 37 publications

Design and characterization of a novel tumor‐homing cell‐penetrating peptide for drug delivery in TGFBR3 high‐expressing tumors

Design and characterization of a novel tumor‐homing cell‐penetrating peptide for drug delivery in TGFBR3 high‐expressing tumors

Effect of α-momordicine on proliferation and apoptosis of liver cancer, and its associated mechanisms of action

Amidated Scolopin‐2 inhibits proliferation and induces apoptosis of Hela cells in vitro and in vivo

Contact Info

Product

Resources

About