PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Differential Induction of Autophagy and Mitochondrial Apoptosis by 2′, 4-Dihydroxy-4′, 6′-Dimethoxy Chalcone Isolated from Chromolaena tacotana, in Breast Cancer Cells
Version 1
: Received: 14 November 2023 / Approved: 14 November 2023 / Online: 16 November 2023 (10:43:38 CET)
How to cite:
Mendez-Callejas, G.; Piñeros-Avila, M.; Celis, C.; Torrenegra, R.; Espinosa-Benitez, A.; Pestana-Nobles, R.; Yosa-Reyes, J. Differential Induction of Autophagy and Mitochondrial Apoptosis by 2′, 4-Dihydroxy-4′, 6′-Dimethoxy Chalcone Isolated from Chromolaena tacotana, in Breast Cancer Cells. Preprints2023, 2023110973. https://doi.org/10.20944/preprints202311.0973.v1
Mendez-Callejas, G.; Piñeros-Avila, M.; Celis, C.; Torrenegra, R.; Espinosa-Benitez, A.; Pestana-Nobles, R.; Yosa-Reyes, J. Differential Induction of Autophagy and Mitochondrial Apoptosis by 2′, 4-Dihydroxy-4′, 6′-Dimethoxy Chalcone Isolated from Chromolaena tacotana, in Breast Cancer Cells. Preprints 2023, 2023110973. https://doi.org/10.20944/preprints202311.0973.v1
Mendez-Callejas, G.; Piñeros-Avila, M.; Celis, C.; Torrenegra, R.; Espinosa-Benitez, A.; Pestana-Nobles, R.; Yosa-Reyes, J. Differential Induction of Autophagy and Mitochondrial Apoptosis by 2′, 4-Dihydroxy-4′, 6′-Dimethoxy Chalcone Isolated from Chromolaena tacotana, in Breast Cancer Cells. Preprints2023, 2023110973. https://doi.org/10.20944/preprints202311.0973.v1
APA Style
Mendez-Callejas, G., Piñeros-Avila, M., Celis, C., Torrenegra, R., Espinosa-Benitez, A., Pestana-Nobles, R., & Yosa-Reyes, J. (2023). Differential Induction of Autophagy and Mitochondrial Apoptosis by 2′, 4-Dihydroxy-4′, 6′-Dimethoxy Chalcone Isolated from Chromolaena tacotana, in Breast Cancer Cells. Preprints. https://doi.org/10.20944/preprints202311.0973.v1
Chicago/Turabian Style
Mendez-Callejas, G., Roberto Pestana-Nobles and Juvenal Yosa-Reyes. 2023 "Differential Induction of Autophagy and Mitochondrial Apoptosis by 2′, 4-Dihydroxy-4′, 6′-Dimethoxy Chalcone Isolated from Chromolaena tacotana, in Breast Cancer Cells" Preprints. https://doi.org/10.20944/preprints202311.0973.v1
Abstract
Breast cancer (BC) ranks among the most prevalent cancers diagnosed in women. Its treatment necessitates precision tailored to the cancer's genetic makeup for enhanced efficacy. Research has been directed towards natural compounds for their anti-BC properties, aiming to augment existing treatment modalities. Chromolaena tacotana (Klatt) R.M. King and H. Rob, commonly referred to as Ch. tacotana, is a notable source of bioactive hydroxy-methylated flavonoids. However, the specific anti-BC mechanisms of these flavonoids, particularly those present in the plant's inflorescences, remain partly undefined. This study focuses on assessing a chalcone derivative extracted from Ch. tacotana inflorescences for its potential to concurrently activate regulated autophagy and intrinsic apoptosis in Luminal A and triple-negative BC cells. We determined the chemical composition of the chalcone using ultraviolet (UV) and nuclear magnetic resonance (NMR) spectroscopy. Its selective cytotoxicity against BC cell lines was assessed using the MTT assay. Flow cytometry and western blot analysis were employed to examine the modulation of proteins governing autophagy and the intrinsic apoptosis pathway. Additionally, in silico simulations were conducted to predict interactions between the chalcone and various anti-apoptotic proteins, including the mTOR protein. The chalcone was identified as 2',4-dihydroxy-4',6'-dimethoxy-chalcone (DDC), also known as Flavokavain C (FKC). This compound demonstrated selective inhibition of BC cell proliferation and triggered autophagy and intrinsic apoptosis. It induced cell cycle arrest in the G0/G1 phase and altered mitochondrial outer membrane potential (∆ψm). The study observed the activation of autophagic LC3-II and mitochondrial pro-apoptotic proteins in both BC cell lines. The regulation of Bcl-XL and Bcl-2 proteins varied according to BC subtype, yet they showed promising molecular interactions with DDC. Among the examined pro-survival proteins, mTOR and Mcl-1 exhibited the most favorable binding energies and were downregulated in MCF-7 and MDA-MB-231 cell lines. Further research is needed to fully understand the molecular dynamics involved in the activation and interaction of autophagy and apoptosis pathways in cancer cells in response to potential anticancer agents like the hydroxy-methylated flavonoids from Ch. tacotana.
Keywords
Chromolaena tacotana; chalcone; breast cancer; intrinsic apoptosis; autophagy
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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