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Molecules 2016, 21(8), 1013; doi:10.3390/molecules21081013

Cytotoxicity, Post-Treatment Recovery, and Selectivity Analysis of Naturally Occurring Podophyllotoxins from Bursera fagaroides var. fagaroides on Breast Cancer Cell Lines

1
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico
2
Centro de Investigación en Biotecnología, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico
3
Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico
*
Author to whom correspondence should be addressed.
Academic Editor: Isabel C. F. R. Ferreira
Received: 26 May 2016 / Revised: 20 July 2016 / Accepted: 27 July 2016 / Published: 4 August 2016
(This article belongs to the Collection Bioactive Compounds)
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Abstract

Despite prevention and treatment options, breast cancer (BC) has become one of the most important issues in the present day. Therefore, the need for more specific and efficient compounds remains paramount. We evaluated four previously isolated aryltetralin lignans: 5′-demethoxy-β-peltatin-A-methylether (1), acetylpodophyllotoxin (2), 5′-demethoxydeoxypodophyllotoxin (3), and 7′,8′-dehydroacetylpodophyllotoxin (4) for cytotoxicity, clonogenicity, and selectivity against three BC cell lines: MCF-7, MDA-MB-231, and BT-549, as well as the non-tumorigenic mammary epithelial cell line MCF-10A. Cytotoxicity was evaluated after 72 h of treatment, and clonogenicity was determined at 72 h post-treatment; experiments were performed using the sulforhodamine B staining assay. Selective-index (SI) was calculated by comparing pure compound IC50 values in MCF-10A cell line against the IC50 of the same compound in cancer cell lines. Structural similarities among lignans and controls (podophyllotoxin and etoposide) were analyzed using the Tanimoto coefficient (Tc). Lignans were cytotoxic against all tested cell lines (0.011–7.22 µM) and clonogenicity testing showed a dose-dependent cytocidality for all lignans (≥0.08 µg/mL); compounds 2 and 3 were more potent (14.1 and 7.6 respectively) than etoposide in BT-549 cell line, while compound 2 displayed selectivity (SI = 28.17) in BT-549 cell line. Tc values of lignans suggested a greater similarity with podophyllotoxin structure. View Full-Text
Keywords: selective-index; Bursera fagaroides; podophyllotoxins selective-index; Bursera fagaroides; podophyllotoxins
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Peña-Morán, O.A.; Villarreal, M.L.; Álvarez-Berber, L.; Meneses-Acosta, A.; Rodríguez-López, V. Cytotoxicity, Post-Treatment Recovery, and Selectivity Analysis of Naturally Occurring Podophyllotoxins from Bursera fagaroides var. fagaroides on Breast Cancer Cell Lines. Molecules 2016, 21, 1013.

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