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JOURNAL ARTICLE

Bacillus thuringiensis toxins are cytotoxic to cervical cancer (HeLa) but not to breast cancer (MCF7) cells

Gretel Mendoza-Almanza, Leticia Rocha-Zavaleta, Cecilia Aguilar-Zacarías, Jorge Ayala-Luján, Jorge Olmos
Current Pharmaceutical Biotechnology 2019 August 2
31376817
Background; Bacillus thuringiensis Cry1A toxins kill insects by interacting with BT-R1 cadherin-like receptors. Also, it has been reported Cry1Ab and Cry1Ac can activate murine macrophages and induce Th1/Th2 immune responses. Objective; The aim of this work was to evaluate the cytotoxicity of Cry1Ab and Cry1Ac on HeLa, SiHa, MCF-7, and HaCat cell lines, as well as anticancer activity in vivo, in tumors induced in nude mice. Method; Cytotoxicity assays were performed from the purified Bacillus thuringiensis toxins in HeLa, SiHa, MCF7, and HaCat. By TUNEL assays we investigate apoptosis as a possible method of action of toxins on cell lines. Finally, the activity of Cry toxin on tumors induced in nude mice was analyzed. Results; Both toxins showed specific cytotoxic activity against HeLa (HPV+ 18) cervical cancer cell line, with LC50 of 2.5 μg/mL and 0.5 μg/mL, respectively. SiHa (HPV+ 16), cervical cancer cell line, MCF-7 breast cancer cell lines and HaCat non-cancerous cell lines were much less sensitive to Cry1A proteins. Apoptosis was differentially induced in HeLa cells using the same amount of Cry1Ab and Cry1Ac proteins. Also, were evaluated the Cry1Ac anticancer activity in vivo, in tumors induced in nude mice, applying 10, 30 and 50 µg/mL every 24 h throughout four days. 50% and 100% tumors elimination were obtained in mice treated with 10 and 30 μg/mL, respectively. Conclusion; Bacillus thuringiensis toxins are able to have a dual cytotoxic action, on insects and on cancer cell lines.

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