Anticancer effect of rationally designed α-helical amphiphilic peptides

Fang Pan, Yueping Li, Yujie Ding, Songwei Lv, Rongrong You, Roja Hadianamrei, Mhd Anas Tomeh, Xiubo Zhao*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Anticancer peptides (ACPs) have attracted increasing attention in cancer therapy due to their unique mechanism of action on cancer cells. The main challenge is to establish the correlation between their physicochemical properties and their selectivity and anticancer effect, leading to a clear design strategy. In this study, a series of new α-helical short peptides (coded At1-At12) with different anticancer activities were systematically designed with different amphiphilicity based on a natural α-helical antimicrobial peptide (AMP) derived from ant. Three of the designed peptides, At7, At10 and At11, showed considerable anticancer activity with low toxicity to normal skin fibroblasts. The high selectivity of the peptides is attributed to their balanced amphiphilicity and cationic nature which favours binding to the outer membrane of negatively charged cancer cells over the neutral membrane of normal mammalian cells. In addition to rapid membrane penetration, the designed peptides also damaged the mitochondria and induced mitochondrial membrane depolarization. Moreover, these peptides were found to induce apoptosis in cancer cells by up-regulating the expression of apoptotic proteins Bax and Caspase-3, down-regulating the apoptotic protein Bcl-2, and activating the Caspase enzyme-linked reaction. The results of this study reveal the potential of these peptides for clinical applications, and provide a guidance for further development of highly selective anticancer medications.
Original languageEnglish
Article number112841
Number of pages9
JournalColloids and Surfaces B Biointerfaces
Early online date26 Sept 2022
Publication statusPublished - 1 Dec 2022


  • Anticancer peptides
  • Amphiphilic peptides
  • Membrane-lytic peptides
  • Membrane disruption
  • Anticancer activity

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