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Assessing the anticancer potential of spider venom peptide Latarcin Ltc2a against triple negative breast cancer
Prasanjeet Kaur1, Srabaita Roy1, Shilpi Minocha1
1Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi 110016, India.
Abstract:
Cancer remains one of the most formidable challenges to human health, necessitating constant exploration of innovative therapeutic strategies. Among the myriad potential candidates, peptides from venom have emerged as potent sources of bioactive molecules possessing diverse pharmacological properties. In this study, we repurposed a spider venom-derived antimicrobial peptide, Ltc2a, into a selective anticancer agent, bridging microbial defense with cancer therapeutics. Our findings reveal that Ltc2a exhibits selective cytotoxicity towards cancer cells compared to normal cells at just 2 μM of the peptide concentration. Ltc2a induced rapid cytotoxicity within 1 h in breast cancer cells and it was accompanied by membrane disruption as shown by propidium iodide (PI) positive staining and visible damage to cancer cell membranes under field emission scanning electron microscopy (FESEM). In vivo studies using a zebrafish model indicated favorable uptake and a lack of acute toxicity, depicting 80 % survival rate up to 4 μM of tested peptide concentration. Interestingly, the truncated variants of Ltc2a retained their alpha helical structure and demonstrated preferential uptake in MDA-MB-231 cells over HEK293T cells. These findings highlight the therapeutic potential of Ltc2a as selective anticancer peptide with minimal toxicity, paving the way for further preclinical development.
Insights
Spider venom peptide Ltc2a shows selective cancer cell killing. This antimicrobial peptide disrupts cancer cell membranes rapidly with minimal toxicity, offering a promising new anticancer therapeutic strategy.
Area of Science:
- Biochemistry
- Pharmacology
- Oncology
Background:
- Cancer poses a significant global health challenge, driving the search for novel therapeutic agents.
- Venom-derived peptides are a rich source of bioactive molecules with potential therapeutic applications.
Purpose of the Study:
- To repurpose the spider venom-derived antimicrobial peptide Ltc2a as a selective anticancer agent.
- To investigate the efficacy and safety of Ltc2a in preclinical cancer models.
Main Methods:
- Assessing Ltc2a cytotoxicity against cancer and normal cells in vitro.
- Evaluating membrane disruption using propidium iodide staining and field emission scanning electron microscopy (FESEM).
- Conducting in vivo toxicity and efficacy studies in a zebrafish model.
Main Results:
- Ltc2a demonstrated selective cytotoxicity towards cancer cells at 2 μM, with rapid effects within 1 hour.
- Membrane disruption was observed in breast cancer cells treated with Ltc2a.
- In vivo studies showed favorable uptake and 80% survival in zebrafish up to 4 μM, indicating low acute toxicity.
- Truncated Ltc2a variants maintained alpha helical structure and showed preferential uptake in cancer cells (MDA-MB-231) over normal cells (HEK293T).
Conclusions:
- Ltc2a is a potent anticancer peptide with selective toxicity against cancer cells and minimal adverse effects.
- The findings support Ltc2a's potential as a novel therapeutic agent for cancer treatment.
- Further preclinical development of Ltc2a is warranted based on its promising efficacy and safety profile.
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