Adenosine derivatives from Cordyceps exert antitumor effects against ovarian cancer cells through ENT1-mediated transport, induction of AMPK signaling, and consequent autophagic cell death

So Young Yoon; Anders M. Lindroth; Soyoung Kwon; Soo Jung Park; Yoon Jung Park

doi:10.1016/j.biopha.2022.113491

Adenosine derivatives from Cordyceps exert antitumor effects against ovarian cancer cells through ENT1-mediated transport, induction of AMPK signaling, and consequent autophagic cell death

So Young Yoon, Anders M. Lindroth, Soyoung Kwon, Soo Jung Park, Yoon Jung Park

Department of Nutritional Science & Food Management

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

9 Scopus citations

Abstract

Cordyceps militaris is rich in adenosine derivatives, including 3′-deoxyadenosine, also known as cordycepin. It has been reported for antitumor effects, but its underlying molecular mechanism has yet to be elucidated. We investigated how adenosine derivatives exerted antitumor effects against ovarian cancer using human ovarian cancer cells and a xenograft mouse model. Treatment with adenosine derivatives effectively resulted in cell death of ovarian cancer cells through AMPK activation and subsequently mTOR-mediated autophagic induction. Intriguingly, the effect required membrane transport of adenosine derivatives via ENT1, rather than ADORA-mediated cellular signaling. Our data suggest that adenosine derivatives may be an effective therapeutic intervention in ovarian cancer through induction of ENT1-AMPK-mTOR-mediated autophagic cell death.

Original language	English
Article number	113491
Journal	Biomedicine and Pharmacotherapy
Volume	153
DOIs	https://doi.org/10.1016/j.biopha.2022.113491
State	Published - Sep 2022

Bibliographical note

Funding Information:
This research was supported by the National Research Foundation of Korea, South Korea (2020R1F1A1076181).We are grateful for support from Dr. Soon Young Shin (Konkuk University, Seoul, Korea), Dr. Jung-Hyuck Ahn (Ewha Womans University, Seoul, Korea), and Dr. Anders M Lindroth (National Cancer Center, Goyang, Korea) for sharing ovarian cancer cell lines and HEK293 cells. We appreciate helps from the Korea Basic Science institute (KBSI) for Bio-TEM analysis. S.Y.Y. was supported by the BK21 FOUR (Fostering Outstanding Universities for Research) funded by the Ministry of Education (MOE, Korea) and National Research Foundation of Korea (NRF-5199990614253), and Health Fellowship Foundation, South Korea.

Funding Information:
We are grateful for support from Dr. Soon Young Shin (Konkuk University, Seoul, Korea), Dr. Jung-Hyuck Ahn (Ewha Womans University, Seoul, Korea), and Dr. Anders M Lindroth (National Cancer Center, Goyang, Korea) for sharing ovarian cancer cell lines and HEK293 cells. We appreciate helps from the Korea Basic Science institute (KBSI) for Bio-TEM analysis. S.Y.Y. was supported by the BK21 FOUR (Fostering Outstanding Universities for Research) funded by the Ministry of Education (MOE, Korea) and National Research Foundation of Korea (NRF- 5199990614253 ), and Health Fellowship Foundation , South Korea.

Funding Information:
This research was supported by the National Research Foundation of Korea , South Korea ( 2020R1F1A1076181 ).

Publisher Copyright:
© 2022

Keywords

Adenosine derivatives
AMPK
Autophagy
Cordyceps militaris
ENT1
Ovarian cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.biopha.2022.113491

Cite this

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title = "Adenosine derivatives from Cordyceps exert antitumor effects against ovarian cancer cells through ENT1-mediated transport, induction of AMPK signaling, and consequent autophagic cell death",

abstract = "Cordyceps militaris is rich in adenosine derivatives, including 3′-deoxyadenosine, also known as cordycepin. It has been reported for antitumor effects, but its underlying molecular mechanism has yet to be elucidated. We investigated how adenosine derivatives exerted antitumor effects against ovarian cancer using human ovarian cancer cells and a xenograft mouse model. Treatment with adenosine derivatives effectively resulted in cell death of ovarian cancer cells through AMPK activation and subsequently mTOR-mediated autophagic induction. Intriguingly, the effect required membrane transport of adenosine derivatives via ENT1, rather than ADORA-mediated cellular signaling. Our data suggest that adenosine derivatives may be an effective therapeutic intervention in ovarian cancer through induction of ENT1-AMPK-mTOR-mediated autophagic cell death.",

keywords = "Adenosine derivatives, AMPK, Autophagy, Cordyceps militaris, ENT1, Ovarian cancer",

author = "Yoon, {So Young} and Lindroth, {Anders M.} and Soyoung Kwon and Park, {Soo Jung} and Park, {Yoon Jung}",

note = "Funding Information: This research was supported by the National Research Foundation of Korea, South Korea (2020R1F1A1076181).We are grateful for support from Dr. Soon Young Shin (Konkuk University, Seoul, Korea), Dr. Jung-Hyuck Ahn (Ewha Womans University, Seoul, Korea), and Dr. Anders M Lindroth (National Cancer Center, Goyang, Korea) for sharing ovarian cancer cell lines and HEK293 cells. We appreciate helps from the Korea Basic Science institute (KBSI) for Bio-TEM analysis. S.Y.Y. was supported by the BK21 FOUR (Fostering Outstanding Universities for Research) funded by the Ministry of Education (MOE, Korea) and National Research Foundation of Korea (NRF-5199990614253), and Health Fellowship Foundation, South Korea. Funding Information: We are grateful for support from Dr. Soon Young Shin (Konkuk University, Seoul, Korea), Dr. Jung-Hyuck Ahn (Ewha Womans University, Seoul, Korea), and Dr. Anders M Lindroth (National Cancer Center, Goyang, Korea) for sharing ovarian cancer cell lines and HEK293 cells. We appreciate helps from the Korea Basic Science institute (KBSI) for Bio-TEM analysis. S.Y.Y. was supported by the BK21 FOUR (Fostering Outstanding Universities for Research) funded by the Ministry of Education (MOE, Korea) and National Research Foundation of Korea (NRF- 5199990614253 ), and Health Fellowship Foundation , South Korea. Funding Information: This research was supported by the National Research Foundation of Korea , South Korea ( 2020R1F1A1076181 ). Publisher Copyright: {\textcopyright} 2022",

year = "2022",

month = sep,

doi = "10.1016/j.biopha.2022.113491",

language = "English",

volume = "153",

journal = "Biomedicine and Pharmacotherapy",

issn = "0753-3322",

publisher = "Elsevier Masson s.r.l.",

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Adenosine derivatives from Cordyceps exert antitumor effects against ovarian cancer cells through ENT1-mediated transport, induction of AMPK signaling, and consequent autophagic cell death. / Yoon, So Young; Lindroth, Anders M.; Kwon, Soyoung et al.
In: Biomedicine and Pharmacotherapy, Vol. 153, 113491, 09.2022.

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

TY - JOUR

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AU - Yoon, So Young

AU - Lindroth, Anders M.

AU - Kwon, Soyoung

AU - Park, Soo Jung

AU - Park, Yoon Jung

N1 - Funding Information: This research was supported by the National Research Foundation of Korea, South Korea (2020R1F1A1076181).We are grateful for support from Dr. Soon Young Shin (Konkuk University, Seoul, Korea), Dr. Jung-Hyuck Ahn (Ewha Womans University, Seoul, Korea), and Dr. Anders M Lindroth (National Cancer Center, Goyang, Korea) for sharing ovarian cancer cell lines and HEK293 cells. We appreciate helps from the Korea Basic Science institute (KBSI) for Bio-TEM analysis. S.Y.Y. was supported by the BK21 FOUR (Fostering Outstanding Universities for Research) funded by the Ministry of Education (MOE, Korea) and National Research Foundation of Korea (NRF-5199990614253), and Health Fellowship Foundation, South Korea. Funding Information: We are grateful for support from Dr. Soon Young Shin (Konkuk University, Seoul, Korea), Dr. Jung-Hyuck Ahn (Ewha Womans University, Seoul, Korea), and Dr. Anders M Lindroth (National Cancer Center, Goyang, Korea) for sharing ovarian cancer cell lines and HEK293 cells. We appreciate helps from the Korea Basic Science institute (KBSI) for Bio-TEM analysis. S.Y.Y. was supported by the BK21 FOUR (Fostering Outstanding Universities for Research) funded by the Ministry of Education (MOE, Korea) and National Research Foundation of Korea (NRF- 5199990614253 ), and Health Fellowship Foundation , South Korea. Funding Information: This research was supported by the National Research Foundation of Korea , South Korea ( 2020R1F1A1076181 ). Publisher Copyright: © 2022

PY - 2022/9

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N2 - Cordyceps militaris is rich in adenosine derivatives, including 3′-deoxyadenosine, also known as cordycepin. It has been reported for antitumor effects, but its underlying molecular mechanism has yet to be elucidated. We investigated how adenosine derivatives exerted antitumor effects against ovarian cancer using human ovarian cancer cells and a xenograft mouse model. Treatment with adenosine derivatives effectively resulted in cell death of ovarian cancer cells through AMPK activation and subsequently mTOR-mediated autophagic induction. Intriguingly, the effect required membrane transport of adenosine derivatives via ENT1, rather than ADORA-mediated cellular signaling. Our data suggest that adenosine derivatives may be an effective therapeutic intervention in ovarian cancer through induction of ENT1-AMPK-mTOR-mediated autophagic cell death.

AB - Cordyceps militaris is rich in adenosine derivatives, including 3′-deoxyadenosine, also known as cordycepin. It has been reported for antitumor effects, but its underlying molecular mechanism has yet to be elucidated. We investigated how adenosine derivatives exerted antitumor effects against ovarian cancer using human ovarian cancer cells and a xenograft mouse model. Treatment with adenosine derivatives effectively resulted in cell death of ovarian cancer cells through AMPK activation and subsequently mTOR-mediated autophagic induction. Intriguingly, the effect required membrane transport of adenosine derivatives via ENT1, rather than ADORA-mediated cellular signaling. Our data suggest that adenosine derivatives may be an effective therapeutic intervention in ovarian cancer through induction of ENT1-AMPK-mTOR-mediated autophagic cell death.

KW - Adenosine derivatives

KW - AMPK

KW - Autophagy

KW - Cordyceps militaris

KW - ENT1

KW - Ovarian cancer

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U2 - 10.1016/j.biopha.2022.113491

DO - 10.1016/j.biopha.2022.113491

M3 - Article

C2 - 36076585

AN - SCOPUS:85135330293

SN - 0753-3322

VL - 153

JO - Biomedicine and Pharmacotherapy

JF - Biomedicine and Pharmacotherapy

M1 - 113491

ER -

Adenosine derivatives from Cordyceps exert antitumor effects against ovarian cancer cells through ENT1-mediated transport, induction of AMPK signaling, and consequent autophagic cell death

Abstract

Bibliographical note

Keywords

UN SDGs

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