Agaritine derived from Agaricus blazei Murrill induces apoptosis via mitochondrial membrane depolarization in hematological tumor cell lines
Objectives: Agaritine (AGT) is a hydrazine-containing compound derived from the mushroom Agaricus blazei Murill. We previously reported the antitumor effect of AGT on hematological tumor cell lines and suggested that AGT induces apoptosis in U937 cells via caspase activation. However, the antitumor...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Fujita Medical Society
2023-05-01
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| Series: | Fujita Medical Journal |
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| Online Access: | https://www.jstage.jst.go.jp/article/fmj/9/2/9_2022-021/_pdf/-char/en |
| _version_ | 1797831746169864192 |
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| author | Atsushi Ogasawara Hiroki Doi Taei Matsui Etsuko Tokunaga Masao Amakawa Hidehiko Akiyama |
| author_facet | Atsushi Ogasawara Hiroki Doi Taei Matsui Etsuko Tokunaga Masao Amakawa Hidehiko Akiyama |
| author_sort | Atsushi Ogasawara |
| collection | DOAJ |
| description | Objectives: Agaritine (AGT) is a hydrazine-containing compound derived from the mushroom Agaricus blazei Murill. We previously reported the antitumor effect of AGT on hematological tumor cell lines and suggested that AGT induces apoptosis in U937 cells via caspase activation. However, the antitumor mechanism of AGT has not been fully understood.
Methods: Four hematological tumor cell lines (K562, HL60, THP-1, H929) were used in this study. The cells were incubated in the presence of 50 μM AGT for 24 h and analyzed for cell viability, annexin V positivity, caspase-3/7 activity, mitochondrial membrane depolarization, cell cycle, DNA fragmentation, and the expression of mitochondrial membrane-associated proteins (Bax and cytochrome c).
Results: In HL60, K562, and H929 cells, AGT reduced cell viability and increased annexin V- and dead cell-positive rates; however, it did not affect THP-1 cells. In K562 and HL60 cells, caspase-3/7 activity, mitochondrial membrane depolarization, and expression of mitochondrial membrane proteins, Bax and cytochrome c, were all increased by AGT. Cell cycle analysis showed that only K562 exhibited an increase in the proportion of cells in G2/M phase after the addition of AGT. DNA fragmentation was also observed after the addition of AGT.
Conclusions: These results indicate that AGT induces apoptosis in K562 and HL60 cells, like U937 reported previously, but showed no effect on THP-1 cells. It was suggested that AGT-induced apoptosis involves the expression of Bax and cytochrome c via mitochondrial membrane depolarization. |
| first_indexed | 2024-04-09T13:56:41Z |
| format | Article |
| id | doaj.art-4ba0f8664bee42cdbb9b15b0f527ee30 |
| institution | Directory Open Access Journal |
| issn | 2189-7247 2189-7255 |
| language | English |
| last_indexed | 2024-04-09T13:56:41Z |
| publishDate | 2023-05-01 |
| publisher | Fujita Medical Society |
| record_format | Article |
| series | Fujita Medical Journal |
| spelling | doaj.art-4ba0f8664bee42cdbb9b15b0f527ee302023-05-08T03:17:20ZengFujita Medical SocietyFujita Medical Journal2189-72472189-72552023-05-0192147153https://doi.org/10.20407/fmj.2022-021Agaritine derived from Agaricus blazei Murrill induces apoptosis via mitochondrial membrane depolarization in hematological tumor cell linesAtsushi Ogasawara0Hiroki Doi1Taei Matsui2Etsuko Tokunaga3Masao Amakawa4Hidehiko Akiyama5Field of Clinical Laboratory Sciences, Fujita Health University, Graduate School of Health SciencesField of Clinical Laboratory Sciences, Fujita Health University, Graduate School of Health SciencesField of Clinical Laboratory Sciences, Fujita Health University, Graduate School of Health SciencesField of Clinical Laboratory Sciences, Fujita Health University, Graduate School of Health SciencesDepartment of Medical Technology, Gifu University of Medical ScienceField of Clinical Laboratory Sciences, Fujita Health University, Graduate School of Health SciencesObjectives: Agaritine (AGT) is a hydrazine-containing compound derived from the mushroom Agaricus blazei Murill. We previously reported the antitumor effect of AGT on hematological tumor cell lines and suggested that AGT induces apoptosis in U937 cells via caspase activation. However, the antitumor mechanism of AGT has not been fully understood. Methods: Four hematological tumor cell lines (K562, HL60, THP-1, H929) were used in this study. The cells were incubated in the presence of 50 μM AGT for 24 h and analyzed for cell viability, annexin V positivity, caspase-3/7 activity, mitochondrial membrane depolarization, cell cycle, DNA fragmentation, and the expression of mitochondrial membrane-associated proteins (Bax and cytochrome c). Results: In HL60, K562, and H929 cells, AGT reduced cell viability and increased annexin V- and dead cell-positive rates; however, it did not affect THP-1 cells. In K562 and HL60 cells, caspase-3/7 activity, mitochondrial membrane depolarization, and expression of mitochondrial membrane proteins, Bax and cytochrome c, were all increased by AGT. Cell cycle analysis showed that only K562 exhibited an increase in the proportion of cells in G2/M phase after the addition of AGT. DNA fragmentation was also observed after the addition of AGT. Conclusions: These results indicate that AGT induces apoptosis in K562 and HL60 cells, like U937 reported previously, but showed no effect on THP-1 cells. It was suggested that AGT-induced apoptosis involves the expression of Bax and cytochrome c via mitochondrial membrane depolarization.https://www.jstage.jst.go.jp/article/fmj/9/2/9_2022-021/_pdf/-char/enagaricus blazei murrillagaritine (agt)apoptosismitochondrial membrane depolarization |
| spellingShingle | Atsushi Ogasawara Hiroki Doi Taei Matsui Etsuko Tokunaga Masao Amakawa Hidehiko Akiyama Agaritine derived from Agaricus blazei Murrill induces apoptosis via mitochondrial membrane depolarization in hematological tumor cell lines Fujita Medical Journal agaricus blazei murrill agaritine (agt) apoptosis mitochondrial membrane depolarization |
| title | Agaritine derived from Agaricus blazei Murrill induces apoptosis via mitochondrial membrane depolarization in hematological tumor cell lines |
| title_full | Agaritine derived from Agaricus blazei Murrill induces apoptosis via mitochondrial membrane depolarization in hematological tumor cell lines |
| title_fullStr | Agaritine derived from Agaricus blazei Murrill induces apoptosis via mitochondrial membrane depolarization in hematological tumor cell lines |
| title_full_unstemmed | Agaritine derived from Agaricus blazei Murrill induces apoptosis via mitochondrial membrane depolarization in hematological tumor cell lines |
| title_short | Agaritine derived from Agaricus blazei Murrill induces apoptosis via mitochondrial membrane depolarization in hematological tumor cell lines |
| title_sort | agaritine derived from agaricus blazei murrill induces apoptosis via mitochondrial membrane depolarization in hematological tumor cell lines |
| topic | agaricus blazei murrill agaritine (agt) apoptosis mitochondrial membrane depolarization |
| url | https://www.jstage.jst.go.jp/article/fmj/9/2/9_2022-021/_pdf/-char/en |
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