Mechanism of Action of Two Flavone Isomers Targeting Cancer Cells with Varying Cell Differentiation Status.
Apoptosis can be triggered in two different ways, through the intrinsic or the extrinsic pathway. The intrinsic pathway is mediated by the mitochondria via the release of cytochrome C while the extrinsic pathway is prompted by death receptor signals and bypasses the mitochondria. These two pathways...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4659548?pdf=render |
| _version_ | 1828405495133634560 |
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| author | Timothy M LeJeune Hei Yin Tsui Laura B Parsons Gerald E Miller Crystal Whitted Kayla E Lynch Robert E Ramsauer Jasmine U Patel Jarrett E Wyatt Doris S Street Carolyn B Adams Brian McPherson Hei Man Tsui Julie A Evans Christopher Livesay Ruben D Torrenegra Victoria E Palau |
| author_facet | Timothy M LeJeune Hei Yin Tsui Laura B Parsons Gerald E Miller Crystal Whitted Kayla E Lynch Robert E Ramsauer Jasmine U Patel Jarrett E Wyatt Doris S Street Carolyn B Adams Brian McPherson Hei Man Tsui Julie A Evans Christopher Livesay Ruben D Torrenegra Victoria E Palau |
| author_sort | Timothy M LeJeune |
| collection | DOAJ |
| description | Apoptosis can be triggered in two different ways, through the intrinsic or the extrinsic pathway. The intrinsic pathway is mediated by the mitochondria via the release of cytochrome C while the extrinsic pathway is prompted by death receptor signals and bypasses the mitochondria. These two pathways are closely related to cell proliferation and survival signaling cascades, which thereby constitute possible targets for cancer therapy. In previous studies we introduced two plant derived isomeric flavonoids, flavone A and flavone B which induce apoptosis in highly tumorigenic cancer cells of the breast, colon, pancreas, and the prostate. Flavone A displayed potent cytotoxic activity against more differentiated carcinomas of the colon (CaCo-2) and the pancreas (Panc28), whereas flavone B cytotoxic action is observed on poorly differentiated carcinomas of the colon (HCT 116) and pancreas (MIA PaCa). Apoptosis is induced by flavone A in better differentiated colon cancer CaCo-2 and pancreatic cancer Panc 28 cells via the intrinsic pathway by the inhibition of the activated forms of extracellular signal-regulated kinase (ERK) and pS6, and subsequent loss of phosphorylation of Bcl-2 associated death promoter (BAD) protein, while apoptosis is triggered by flavone B in poorly differentiated colon cancer HCT 116 and MIA PaCa pancreatic cancer cells through the extrinsic pathway with the concomitant upregulation of the phosphorylated forms of ERK and c-JUN at serine 73. These changes in protein levels ultimately lead to activation of apoptosis, without the involvement of AKT. |
| first_indexed | 2024-12-10T10:54:23Z |
| format | Article |
| id | doaj.art-ff2eb67b98f4422ea6b50621b8452d8f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T10:54:23Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ff2eb67b98f4422ea6b50621b8452d8f2022-12-22T01:51:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011011e014292810.1371/journal.pone.0142928Mechanism of Action of Two Flavone Isomers Targeting Cancer Cells with Varying Cell Differentiation Status.Timothy M LeJeuneHei Yin TsuiLaura B ParsonsGerald E MillerCrystal WhittedKayla E LynchRobert E RamsauerJasmine U PatelJarrett E WyattDoris S StreetCarolyn B AdamsBrian McPhersonHei Man TsuiJulie A EvansChristopher LivesayRuben D TorrenegraVictoria E PalauApoptosis can be triggered in two different ways, through the intrinsic or the extrinsic pathway. The intrinsic pathway is mediated by the mitochondria via the release of cytochrome C while the extrinsic pathway is prompted by death receptor signals and bypasses the mitochondria. These two pathways are closely related to cell proliferation and survival signaling cascades, which thereby constitute possible targets for cancer therapy. In previous studies we introduced two plant derived isomeric flavonoids, flavone A and flavone B which induce apoptosis in highly tumorigenic cancer cells of the breast, colon, pancreas, and the prostate. Flavone A displayed potent cytotoxic activity against more differentiated carcinomas of the colon (CaCo-2) and the pancreas (Panc28), whereas flavone B cytotoxic action is observed on poorly differentiated carcinomas of the colon (HCT 116) and pancreas (MIA PaCa). Apoptosis is induced by flavone A in better differentiated colon cancer CaCo-2 and pancreatic cancer Panc 28 cells via the intrinsic pathway by the inhibition of the activated forms of extracellular signal-regulated kinase (ERK) and pS6, and subsequent loss of phosphorylation of Bcl-2 associated death promoter (BAD) protein, while apoptosis is triggered by flavone B in poorly differentiated colon cancer HCT 116 and MIA PaCa pancreatic cancer cells through the extrinsic pathway with the concomitant upregulation of the phosphorylated forms of ERK and c-JUN at serine 73. These changes in protein levels ultimately lead to activation of apoptosis, without the involvement of AKT.http://europepmc.org/articles/PMC4659548?pdf=render |
| spellingShingle | Timothy M LeJeune Hei Yin Tsui Laura B Parsons Gerald E Miller Crystal Whitted Kayla E Lynch Robert E Ramsauer Jasmine U Patel Jarrett E Wyatt Doris S Street Carolyn B Adams Brian McPherson Hei Man Tsui Julie A Evans Christopher Livesay Ruben D Torrenegra Victoria E Palau Mechanism of Action of Two Flavone Isomers Targeting Cancer Cells with Varying Cell Differentiation Status. PLoS ONE |
| title | Mechanism of Action of Two Flavone Isomers Targeting Cancer Cells with Varying Cell Differentiation Status. |
| title_full | Mechanism of Action of Two Flavone Isomers Targeting Cancer Cells with Varying Cell Differentiation Status. |
| title_fullStr | Mechanism of Action of Two Flavone Isomers Targeting Cancer Cells with Varying Cell Differentiation Status. |
| title_full_unstemmed | Mechanism of Action of Two Flavone Isomers Targeting Cancer Cells with Varying Cell Differentiation Status. |
| title_short | Mechanism of Action of Two Flavone Isomers Targeting Cancer Cells with Varying Cell Differentiation Status. |
| title_sort | mechanism of action of two flavone isomers targeting cancer cells with varying cell differentiation status |
| url | http://europepmc.org/articles/PMC4659548?pdf=render |
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