A New Flavanone from Chromolaena tacotana (Klatt) R. M. King and H. Rob, Promotes Apoptosis in Human Breast Cancer Cells by Downregulating Antiapoptotic Proteins

Méndez-Callejas, Gina; Torrenegra, Rubén; Muñoz-Cendales, Diego Ricardo; Celis, Crispín; Roso, Michael; Garzon, Jojhan; Beltran, Ferney; Cárdenas, Andrés

doi:10.3390/molecules28010058

Cited by 4 publications

(12 citation statements)

References 36 publications

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“…Some flavanones and their derivatives possess anticancer activities. Tacotanina, a 3 ′ ,4 ′ -dihydroxy-5,7-dimethoxyflavonone isolated from the leaves of Chromolaena tacotana, inhibits the cell proliferation of triple-negative human breast cancer cell lines MDA-MB-231 and MCF-7 [54]. The scientists noted a significant inactivation of the anti-apoptotic protein Bcl-2 and the activation of effector caspase-3 and/or 7 within the breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Methyl-Derivatives of Flavanone on MCP-1, MIP-1β, RANTES, and Eotaxin Release by Activated RAW264.7 Macrophages

Kłósek,

Kurek-Górecka,

Balwierz

et al. 2024

Molecules

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Chemokines, also known as chemotactic cytokines, stimulate the migration of immune cells. These molecules play a key role in the pathogenesis of inflammation leading to atherosclerosis, neurodegenerative disorders, rheumatoid arthritis, insulin-resistant diabetes, and cancer. Moreover, they take part in inflammatory bowel disease (IBD). The main objective of our research was to determine the activity of methyl-derivatives of flavanone, namely, 2′-methylflavanone (5B), 3′-methylflavanone (6B), 4′-methylflavanone (7B), and 6-methylflavanone (8B), on the releasing of selected cytokines by RAW264.7 macrophages activated by LPS. We determined the concentration of chemokines belonging to the CC chemokine family, namely, MCP-1, MIP-1β, RANTES, and eotaxin, using the Bio-Plex Magnetic Luminex Assay and the Bio-PlexTM 200 System. Among the tested compounds, only 5B and 6B had the strongest effect on inhibiting the examined chemokines’ release by macrophages. Therefore, 5B and 6B appear to be potentially useful in the prevention of diseases associated with the inflammatory process.

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Section: Discussionmentioning

confidence: 99%

The Effect of Methyl-Derivatives of Flavanone on MCP-1, MIP-1β, RANTES, and Eotaxin Release by Activated RAW264.7 Macrophages

Kłósek,

Kurek-Górecka,

Balwierz

et al. 2024

Molecules

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“…Previous research indicates that natural chalcones, including butein, xanthohumol, isoliquiritigenin, chalcotanina, and flavokawains, may exhibit cytotoxic effects, particularly inducing apoptosis in breast cancer (BC) cells [ 17 , 28 , 43 , 45 ]. However, prior to this study, there was no evidence demonstrating the simultaneous induction of both apoptosis and autophagy in BC cells by flavokawains (FKCs).…”

Section: Discussionmentioning

confidence: 99%

“…The induction of apoptosis by chalcones, particularly through the activation of caspase-3, is a well-documented phenomenon [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ]. In our study, the data suggested that DDC preferentially activated caspase-3 over caspase-7 in MDA-MB-231 cells, as illustrated in Figure 5 .…”

Section: Discussionmentioning

confidence: 99%

“…Following primary antibody incubation, the membranes were incubated for 2 h at room temperature with either anti-mouse IgG or anti-rabbit IgG secondary antibodies (1:5000) (Merck Group, Darmstadt, Germany) [ 28 ]. Bands were visualized using the 1-Step™ TMB-Blotting Substrate Solution (Thermo-Fisher Scientific, Waltham, MA, USA), which generates a blue precipitate.…”

Section: Methodsmentioning

confidence: 99%

“…tacotana ) is an endemic plant in Colombia, a source of flavonoids with antiproliferative properties [ 26 ] that depends on the position of the hydroxyl groups in the molecule’s structure [ 27 ]. Recently identified flavonoids, such as 3′,4′-dihydroxy-5,7-dimethoxy-flavanone and 2′,3,4-trihydroxy-4′,6′-dimethoxychalcone, exhibit significant antiproliferative activity against cancer cells, particularly TNBC [ 28 , 29 ]. Chalcotanina induces autophagy by affecting the structural conformation of the mTOR protein and apoptosis through the activation of caspases 3/7.…”

Section: Introductionmentioning

confidence: 99%

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Natural 2′,4-Dihydroxy-4′,6′-dimethoxy Chalcone Isolated from Chromolaena tacotana Inhibits Breast Cancer Cell Growth through Autophagy and Mitochondrial Apoptosis

Mendez-Callejas,

Piñeros-Avila,

Celis

et al. 2024

Plants

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Breast cancer (BC) is one of the most common cancers among women. Effective treatment requires precise tailoring to the genetic makeup of the cancer for improved efficacy. Numerous research studies have concentrated on natural compounds and their anti-breast cancer properties to improve the existing treatment options. Chromolaena tacotana (Klatt) R.M. King and H. Rob (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 chalcone and various anti-apoptotic proteins, including the mTOR protein. Chalcone was identified as 2′,4-dihydroxy-4′,6′-dimethoxy-chalcone (DDC). This compound demonstrated a 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 detected 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 the 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 BC 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.

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Differential Induction of Autophagy and Mitochondrial Apoptosis by 2′, 4-Dihydroxy-4′, 6′-Dimethoxy Chalcone Isolated from Chromolaena tacotana, in Breast Cancer Cells

Mendez-Callejas,

Piñeros-Avila,

Celis

et al. 2023

Preprint

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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.

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A New Flavanone from Chromolaena tacotana (Klatt) R. M. King and H. Rob, Promotes Apoptosis in Human Breast Cancer Cells by Downregulating Antiapoptotic Proteins

Cited by 4 publications

References 36 publications

The Effect of Methyl-Derivatives of Flavanone on MCP-1, MIP-1β, RANTES, and Eotaxin Release by Activated RAW264.7 Macrophages

The Effect of Methyl-Derivatives of Flavanone on MCP-1, MIP-1β, RANTES, and Eotaxin Release by Activated RAW264.7 Macrophages

Natural 2′,4-Dihydroxy-4′,6′-dimethoxy Chalcone Isolated from Chromolaena tacotana Inhibits Breast Cancer Cell Growth through Autophagy and Mitochondrial Apoptosis

Differential Induction of Autophagy and Mitochondrial Apoptosis by 2′, 4-Dihydroxy-4′, 6′-Dimethoxy Chalcone Isolated from Chromolaena tacotana, in Breast Cancer Cells

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