SK&F 96365 induces apoptosis and autophagy by inhibiting Akt-mTOR signaling in A7r5 cells

Eun Jung Park; Sang Yeob Kim; Su Hwa Kim; Chae Ryun Lee; In San Kim; Jong Kwan Park; Sung Won Lee; Byung Joo Kim; Jung Nyeo Chun; Insuk So; Ju Hong Jeon

doi:10.1016/j.bbamcr.2011.06.021

SK&F 96365 induces apoptosis and autophagy by inhibiting Akt-mTOR signaling in A7r5 cells

Eun Jung Park, Sang Yeob Kim, Su Hwa Kim, Chae Ryun Lee, In San Kim, Jong Kwan Park, Sung Won Lee, Byung Joo Kim, Jung Nyeo Chun, Insuk So, Ju Hong Jeon

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

Abstract

SK&F 96365 has been widely used as an inhibitor of transient receptor potential (TRP) calcium channels in various physiological settings. However, growing evidence suggests that SK&F 96365 affects several cellular and molecular processes via uncharacterized off-target mechanisms. In this study, we showed that SK&F 96365 induces apoptosis and autophagy in A7r5 vascular smooth muscle cells. The combined suppression of apoptosis and autophagy provoked necrosis rather than rescued cell death in the cells treated with SK&F 96365. In addition, we found that SK&F 96365 inhibits Akt-mTOR signaling pathways, which is comparable with the efficacy of other known Akt inhibitors. Our findings suggest that SK&F 96365 can be a useful agent for delineating the molecular mechanisms underlying crosstalk among cell death pathways.

Original language	English
Pages (from-to)	2157-2164
Number of pages	8
Journal	Biochimica et Biophysica Acta - Molecular Cell Research
Volume	1813
Issue number	12
DOIs	https://doi.org/10.1016/j.bbamcr.2011.06.021
Publication status	Published - 2011 Dec
Externally published	Yes

Bibliographical note

Funding Information:
A plasmid for caspase-3 FRET-based indicator (SCAT3) was kindly provided by Prof. Takeharu Nagai from Hokkaido University in Japan. This study was supported by a grant of the Korea Health 21R&D project, Ministry of Health, Welfare and Family Affairs, Republic of Korea ( A090583 ).

Keywords

Akt-mTOR signaling
Apoptosis
Autophagy
SK&F 96365
TRP channel

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.bbamcr.2011.06.021

Cite this

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title = "SK&F 96365 induces apoptosis and autophagy by inhibiting Akt-mTOR signaling in A7r5 cells",

abstract = "SK&F 96365 has been widely used as an inhibitor of transient receptor potential (TRP) calcium channels in various physiological settings. However, growing evidence suggests that SK&F 96365 affects several cellular and molecular processes via uncharacterized off-target mechanisms. In this study, we showed that SK&F 96365 induces apoptosis and autophagy in A7r5 vascular smooth muscle cells. The combined suppression of apoptosis and autophagy provoked necrosis rather than rescued cell death in the cells treated with SK&F 96365. In addition, we found that SK&F 96365 inhibits Akt-mTOR signaling pathways, which is comparable with the efficacy of other known Akt inhibitors. Our findings suggest that SK&F 96365 can be a useful agent for delineating the molecular mechanisms underlying crosstalk among cell death pathways.",

keywords = "Akt-mTOR signaling, Apoptosis, Autophagy, SK&F 96365, TRP channel",

author = "Park, {Eun Jung} and Kim, {Sang Yeob} and Kim, {Su Hwa} and Lee, {Chae Ryun} and Kim, {In San} and Park, {Jong Kwan} and Lee, {Sung Won} and Kim, {Byung Joo} and Chun, {Jung Nyeo} and Insuk So and Jeon, {Ju Hong}",

note = "Funding Information: A plasmid for caspase-3 FRET-based indicator (SCAT3) was kindly provided by Prof. Takeharu Nagai from Hokkaido University in Japan. This study was supported by a grant of the Korea Health 21R&D project, Ministry of Health, Welfare and Family Affairs, Republic of Korea ( A090583 ). ",

year = "2011",

month = dec,

doi = "10.1016/j.bbamcr.2011.06.021",

language = "English",

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AU - Park, Eun Jung

AU - Kim, Sang Yeob

AU - Kim, Su Hwa

AU - Lee, Chae Ryun

AU - Kim, In San

AU - Park, Jong Kwan

AU - Lee, Sung Won

AU - Kim, Byung Joo

AU - Chun, Jung Nyeo

AU - So, Insuk

AU - Jeon, Ju Hong

N1 - Funding Information: A plasmid for caspase-3 FRET-based indicator (SCAT3) was kindly provided by Prof. Takeharu Nagai from Hokkaido University in Japan. This study was supported by a grant of the Korea Health 21R&D project, Ministry of Health, Welfare and Family Affairs, Republic of Korea ( A090583 ).

PY - 2011/12

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N2 - SK&F 96365 has been widely used as an inhibitor of transient receptor potential (TRP) calcium channels in various physiological settings. However, growing evidence suggests that SK&F 96365 affects several cellular and molecular processes via uncharacterized off-target mechanisms. In this study, we showed that SK&F 96365 induces apoptosis and autophagy in A7r5 vascular smooth muscle cells. The combined suppression of apoptosis and autophagy provoked necrosis rather than rescued cell death in the cells treated with SK&F 96365. In addition, we found that SK&F 96365 inhibits Akt-mTOR signaling pathways, which is comparable with the efficacy of other known Akt inhibitors. Our findings suggest that SK&F 96365 can be a useful agent for delineating the molecular mechanisms underlying crosstalk among cell death pathways.

AB - SK&F 96365 has been widely used as an inhibitor of transient receptor potential (TRP) calcium channels in various physiological settings. However, growing evidence suggests that SK&F 96365 affects several cellular and molecular processes via uncharacterized off-target mechanisms. In this study, we showed that SK&F 96365 induces apoptosis and autophagy in A7r5 vascular smooth muscle cells. The combined suppression of apoptosis and autophagy provoked necrosis rather than rescued cell death in the cells treated with SK&F 96365. In addition, we found that SK&F 96365 inhibits Akt-mTOR signaling pathways, which is comparable with the efficacy of other known Akt inhibitors. Our findings suggest that SK&F 96365 can be a useful agent for delineating the molecular mechanisms underlying crosstalk among cell death pathways.

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KW - Autophagy

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SK&F 96365 induces apoptosis and autophagy by inhibiting Akt-mTOR signaling in A7r5 cells

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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