Title:Cry1A Proteins are Cytotoxic to HeLa but not to SiHa Cervical Cancer Cells
Volume: 20
Issue: 12
Author(s): Gretel Mendoza-Almanza, Leticia Rocha-Zavaleta, Cecilia Aguilar-Zacarías, Jorge Ayala-Luján and Jorge Olmos*
Affiliation:
- Departamento de Biotecnologia Marina, Centro de Investigacion Científica y Educacion Superior de Ensenada, Ensenada,Mexico
Keywords:
Bacillus thuringiensis, cytotoxicity, cancer cells, apoptosis, antitumoral activity, toxins.
Abstract:
Background: Bacillus thuringiensis toxins are effective against multiple biological targets
such as insects, nematodes, mites, protozoa, and importantly, human cancer cells. One of the main
mechanisms by which Cry toxins to trigger cell death is the specific recognition of cadherin-like membrane
cell receptors.
Objective: This work aimed to assess the cytotoxicity of the Cry1Ab and Cry1Ac toxins from Bacillus
thuringiensis in HeLa, cervical cancer cell line, as well as their antitumor activity in mouse models.
Methods: We analyzed several biological targets of Cry1Ab and Cry1Ac including erythrocytes, insect
larvae, as well as cancer and non-cancer cell lines. The viability of HeLa, SiHa, MCF7 and HaCat cells
was assessed by MTT 24 h after the administration of Cry toxins. We also studied apoptosis as a possible
cytotoxicity mechanism in HeLa. The capacity of Cry toxins to eliminate tumors in xenograft
mouse models was also analyzed.
Results: Both toxins, Cry1Ab and Cry1Ac, showed specific cytotoxic activity in HeLa (HPV18+) cervical
cancer cell line, with a Cry1Ab LC50 of 2.5 µg/ml, and of 0.5 µg/ml for Cry1Ac. Apoptosis was
differentially induced in HeLa cells using the same concentration of Cry1Ab and Cry1Ac toxins. Cry1Ac
eliminated 50% of the tumors at 10 µg/ml, and eliminate 100% of the tumors at 30 and 50 µg/ml.
Conclusion: Bacillus thuringiensis Cry1A toxins show dual cytotoxic activity, in insects as well as in
HeLa cancer cell line.
