Anti-proliferative activity and apoptotic effect of tick salivary gland extracts on human HeLa cells
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Updated: Jul 18, 2026

Extraction of Saliva, Haemolymph, Salivary Glands, and Midgut from Individual Ticks (Acari: Ixodidae)
Published on: October 31, 2025
Maria Kazimírová1, Ima Dovinová, Terézia Rolníková
1Institute of Zoology, Slovak Academy of Sciences, Bratislava, Slovakia. maria.kazimirova@savba.sk
Objectives:
The anti-proliferative and apoptotic potential of salivary gland extracts (SGE) of unfed and partially fed adult ixodid ticks were screened using human HeLa cells.
Methods:
Cell growth inhibition activity of SGE was measured by the MTT assay. Cell cycle analysis and quantification of DNA fragmentation was performed by DNA staining with propidium iodide. Annexin V-FITC was used to detect apoptotic cells.
Results:
SGE of all ticks examined suppressed HeLa cell proliferation in a dose dependent manner. Extracts from 2-day fed R. appendiculatus females (IC(50) 0.22 mg/ml SGE soluble protein) and 9-day fed A. variegatum females (IC(50) 0.30 mg/ml) were most potent. Species-specific differences in the anti-proliferative effects of SGE were revealed, suggesting that the amount of active compounds in tick salivary glands change during feeding. Total apoptosis (about 12%) and no significant alteration in cell cycle were confirmed for SGE of A. variegatum and R. appendiculatus, and additionally SGE of 5-day fed I. ricinus females (IC(50) 0.64 mg/ml).
Conclusions:
The study shows that tumour cell growth suppressant(s) and/or apoptotic triggers are present in tick salivary glands, however, further research into the characteristics and mode of action of such natural substances is necessary.
Insights
Tick salivary gland extracts (SGE) inhibit tumor cell proliferation and induce apoptosis. Potent anti-cancer compounds were identified in SGE from fed ticks, necessitating further research into their therapeutic potential.
Area of Science:
- Parasitology
- Molecular Biology
- Cell Biology
Background:
- Ixodid ticks possess salivary glands that secrete bioactive compounds during feeding.
- These compounds play a role in host immune modulation and pathogen transmission.
- The potential anti-cancer properties of tick salivary gland extracts (SGE) are largely unexplored.
Purpose of the Study:
- To investigate the anti-proliferative and apoptotic effects of SGE from unfed and partially fed adult ixodid ticks on human cancer cells.
- To identify specific tick feeding stages and species with potent anti-cancer activity in their SGE.
Main Methods:
- Human cervical cancer cells (HeLa) were treated with SGE from various tick species and feeding statuses.
- Cell proliferation was assessed using the MTT assay.
- Apoptosis and cell cycle progression were analyzed via Annexin V-FITC staining, propidium iodide DNA staining, and flow cytometry.
Main Results:
- SGE from all tested ticks demonstrated dose-dependent inhibition of HeLa cell proliferation.
- The most potent anti-proliferative activity was observed in SGE from 2-day fed Rhipicephalus appendiculatus (IC50 0.22 mg/ml) and 9-day fed Amblyomma variegatum (IC50 0.30 mg/ml) females.
- SGE from A. variegatum, R. appendiculatus, and 5-day fed Ixodes ricinus (IC50 0.64 mg/ml) induced significant apoptosis (approx. 12%) without altering cell cycle distribution.
Conclusions:
- Tick salivary glands contain substances with tumor cell growth suppressive and/or apoptotic-inducing properties.
- The anti-cancer activity of SGE varies between tick species and is influenced by feeding duration.
- Further investigation is warranted to characterize these natural compounds and elucidate their mechanisms of action for potential therapeutic applications.

