ePoster Display session ePoster

44P - Investigation of scorpion venom-derived anticancer peptides inhibition of metastatic cancer cells growth and induction of apoptosis (ID 224)

Presentation Number
44P
Lecture Time
10:01 - 10:01
Speakers
  • Yin-Quan Tang (Subang Jaya, Malaysia)
Session Name
ePoster Display session
Room
ePoster gallery
Date
Tue, 02.03.2021
Time
08:00 - 20:00
Authors
  • Yin-Quan Tang (Subang Jaya, Malaysia)
  • TSUEY NING Soon (SUBANG JAYA, Malaysia)

Abstract

Background

Cancer is the second leading cause of death globally and the rise in treatment-resistant cancer cells make treatments for cancer difficult. Several studies have showed the importance of cationic peptides as a potential candidate for anticancer therapeutics. More recently, scorpion venom has emerged to be an important source of peptide candidates targeting human diseases including cancer. The peptide of mauripon produced from Androctonus mauritanicus scorpion, showing a promising candidates anticancer property was explored.

Methods

A list of 34 overlapping short peptides (MDs) was generated by taking 15 amino acids from the N-terminal of mature mauriporin. Among these MDs, M1 with the most potent predicted anticancer activity with low toxicity and haemolytic activities, was selected for hydrophobic modification to produce a series of improved anticancer peptide (M1.1-M1.6). The in-vitro validation of antiproliferation activity of these M1.1-M1.6 peptides on different metastatic cancer cells was studied. The interaction of M1.1-M1.6 peptides with different anti-apoptotic Bcl-2 family proteins was investigated to elucidate its potential to induce apoptotic cell death.

Results

The selective antiproliferation activity of M1.2 (with Ala substitution) was observed by targeting only metatstatic cancer cells without interupting normal cells’ viability. As comparison to other peptides and apoptotic-inducer drug (venetoclax) in protein-peptide studies, M1.2 showed greatest binding efficacy towards Bcl-2, Bcl-xL and Mcl-1 thus inhibiting their anti-apoptotic functions. Moreover, the activation of p53-independent intrinsic apoptosis by M1.2 was observed by the activation of caspase-9 in p53-null and mutant cell lines, as well as low LDH leakage at 24 hours.

Conclusions

In this study, the hydrophobic modification in peptides resulted in an increased anticancer activity and induction of apoptosis that is distinct from the necrotic effect of parental mauriporin peptide. Together, this study provided insights about the development and design strategy of peptide fragment-based drug from animal venom, which can be further exercised in screening potential anticancer peptide targeting cancer.

Legal entity responsible for the study

The authors.

Funding

Taylor’s Research Grant Scheme.

Disclosure

All authors have declared no conflicts of interest.

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