Discovery of a synthetic taiwaniaquinoid with potent in vitro and in vivo antitumor activity against breast cancer cells
Taiwaniaquinoids are a unique family of diterpenoids predominantly isolated from Taiwania cryptomerioides Hayata. Previously, we evaluated the antiproliferative effect of several synthetic taiwaniaquinoids against human lung (A-549), colon (T-84), and breast (MCF-7) tumor cell lines. Herein, we repo...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223015895 |
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| author | Nuria Mut-Salud Juan J. Guardia Antonio Fernández Isabel Blancas Houda Zentar José M. Garrido Enrique Álvarez-Manzaneda Rachid Chahboun Fernando Rodríguez-Serrano |
| author_facet | Nuria Mut-Salud Juan J. Guardia Antonio Fernández Isabel Blancas Houda Zentar José M. Garrido Enrique Álvarez-Manzaneda Rachid Chahboun Fernando Rodríguez-Serrano |
| author_sort | Nuria Mut-Salud |
| collection | DOAJ |
| description | Taiwaniaquinoids are a unique family of diterpenoids predominantly isolated from Taiwania cryptomerioides Hayata. Previously, we evaluated the antiproliferative effect of several synthetic taiwaniaquinoids against human lung (A-549), colon (T-84), and breast (MCF-7) tumor cell lines. Herein, we report the in vitro and in vivo antitumor activity of the most potent compounds. Their cytotoxic activity against healthy peripheral blood mononuclear cells (PBMCs) has also been examined. We underscore the limited toxicity of compound C36 in PBMCs and demonstrate that it exerts its antitumor effect in MCF-7 cells (IC50 = 1.8 µM) by triggering an increase in reactive oxygen species, increasing the cell population in the sub-G1 phase of the cell cycle (90 %), and ultimately activating apoptotic (49.6 %) rather than autophagic processes. Western blot results suggested that the underlying mechanism of the C36 apoptotic effects was linked to caspase 9 activation and a rise in the Bax/Bcl-2 ratio. In vivo analyses showed normal behavior and hematological parameters in C57BL/6 mice post C36 treatment. Moreover, no significant impact was observed on the biochemical parameters of these animals, indicating that C36 did not induce liver toxicity. Furthermore, C36 demonstrated a significant reduction in tumor growth in immune-competent C57BL/6 mice implanted with E0771 mouse mammary tumor cells, effectively improving survival rates. These findings position taiwaniaquinoids, particularly compound C36, as promising therapeutic candidates for human breast cancer. |
| first_indexed | 2024-03-11T11:10:23Z |
| format | Article |
| id | doaj.art-3fff4c78832e4b91807f28d3e7064a15 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-11T11:10:23Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-3fff4c78832e4b91807f28d3e7064a152023-11-12T04:39:20ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-12-01168115791Discovery of a synthetic taiwaniaquinoid with potent in vitro and in vivo antitumor activity against breast cancer cellsNuria Mut-Salud0Juan J. Guardia1Antonio Fernández2Isabel Blancas3Houda Zentar4José M. Garrido5Enrique Álvarez-Manzaneda6Rachid Chahboun7Fernando Rodríguez-Serrano8Biopathology and Regenerative Medicine Institute (IBIMER), University of Granada, Granada 18016, SpainDepartment of Organic Chemistry, Faculty of Sciences, University of Granada, Granada 18071, SpainDepartment of Organic Chemistry, Faculty of Sciences, University of Granada, Granada 18071, SpainBiopathology and Regenerative Medicine Institute (IBIMER), University of Granada, Granada 18016, Spain; Department of Medicine, School of Medicine, University of Granada, Granada 18016, Spain; Department of Medical Oncology, San Cecilio University Hospital, Granada 18016, Spain; Biosanitary Research Institute of Granada (ibs.GRANADA), Granada 18014, SpainDepartment of Organic Chemistry, Faculty of Sciences, University of Granada, Granada 18071, SpainBiopathology and Regenerative Medicine Institute (IBIMER), University of Granada, Granada 18016, Spain; Biosanitary Research Institute of Granada (ibs.GRANADA), Granada 18014, Spain; Department of Surgery and Surgical Specialties, University of Granada, Granada 18016, SpainDepartment of Organic Chemistry, Faculty of Sciences, University of Granada, Granada 18071, SpainDepartment of Organic Chemistry, Faculty of Sciences, University of Granada, Granada 18071, Spain; Correspondence to: University of Granada, Department of Organic Chemistry, Faculty of Science, C/Fuentenueva s/n, 18071 Granada, Spain.Biopathology and Regenerative Medicine Institute (IBIMER), University of Granada, Granada 18016, Spain; Biosanitary Research Institute of Granada (ibs.GRANADA), Granada 18014, Spain; Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada 18016, Spain; Correspondence to: University of Granada, Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, Avda. del Conocimiento s/n Armilla, 18016 Granada, Spain.Taiwaniaquinoids are a unique family of diterpenoids predominantly isolated from Taiwania cryptomerioides Hayata. Previously, we evaluated the antiproliferative effect of several synthetic taiwaniaquinoids against human lung (A-549), colon (T-84), and breast (MCF-7) tumor cell lines. Herein, we report the in vitro and in vivo antitumor activity of the most potent compounds. Their cytotoxic activity against healthy peripheral blood mononuclear cells (PBMCs) has also been examined. We underscore the limited toxicity of compound C36 in PBMCs and demonstrate that it exerts its antitumor effect in MCF-7 cells (IC50 = 1.8 µM) by triggering an increase in reactive oxygen species, increasing the cell population in the sub-G1 phase of the cell cycle (90 %), and ultimately activating apoptotic (49.6 %) rather than autophagic processes. Western blot results suggested that the underlying mechanism of the C36 apoptotic effects was linked to caspase 9 activation and a rise in the Bax/Bcl-2 ratio. In vivo analyses showed normal behavior and hematological parameters in C57BL/6 mice post C36 treatment. Moreover, no significant impact was observed on the biochemical parameters of these animals, indicating that C36 did not induce liver toxicity. Furthermore, C36 demonstrated a significant reduction in tumor growth in immune-competent C57BL/6 mice implanted with E0771 mouse mammary tumor cells, effectively improving survival rates. These findings position taiwaniaquinoids, particularly compound C36, as promising therapeutic candidates for human breast cancer.http://www.sciencedirect.com/science/article/pii/S0753332223015895TaiwaniaquinoidsCancerApoptosisCell cycle arrestOxidative stressIn vivo |
| spellingShingle | Nuria Mut-Salud Juan J. Guardia Antonio Fernández Isabel Blancas Houda Zentar José M. Garrido Enrique Álvarez-Manzaneda Rachid Chahboun Fernando Rodríguez-Serrano Discovery of a synthetic taiwaniaquinoid with potent in vitro and in vivo antitumor activity against breast cancer cells Biomedicine & Pharmacotherapy Taiwaniaquinoids Cancer Apoptosis Cell cycle arrest Oxidative stress In vivo |
| title | Discovery of a synthetic taiwaniaquinoid with potent in vitro and in vivo antitumor activity against breast cancer cells |
| title_full | Discovery of a synthetic taiwaniaquinoid with potent in vitro and in vivo antitumor activity against breast cancer cells |
| title_fullStr | Discovery of a synthetic taiwaniaquinoid with potent in vitro and in vivo antitumor activity against breast cancer cells |
| title_full_unstemmed | Discovery of a synthetic taiwaniaquinoid with potent in vitro and in vivo antitumor activity against breast cancer cells |
| title_short | Discovery of a synthetic taiwaniaquinoid with potent in vitro and in vivo antitumor activity against breast cancer cells |
| title_sort | discovery of a synthetic taiwaniaquinoid with potent in vitro and in vivo antitumor activity against breast cancer cells |
| topic | Taiwaniaquinoids Cancer Apoptosis Cell cycle arrest Oxidative stress In vivo |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223015895 |
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