A Natural CHI3L1—Targeting Compound, Ebractenoid F, Inhibits Lung Cancer Cell Growth and Migration and Induces Apoptosis by Blocking CHI3L1/AKT Signals

Our previous big data analyses reported a strong association between CHI3L1 expression and lung tumor development. In this present study, we investigated whether a CHI3L1-inhibiting natural compound, ebractenoid F, inhibits lung cancer cell growth and migration and induces apoptosis. Ebractenoid F c...

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Main Authors: Da Eun Hong, Ji Eun Yu, Jin Woo Lee, Dong Ju Son, Hee Pom Lee, Yuri Kim, Ju Young Chang, Dong Won Lee, Won Kyu Lee, Jaesuk Yun, Sang Bae Han, Bang Yeon Hwang, Jin Tae Hong
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/28/1/329
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author Da Eun Hong
Ji Eun Yu
Jin Woo Lee
Dong Ju Son
Hee Pom Lee
Yuri Kim
Ju Young Chang
Dong Won Lee
Won Kyu Lee
Jaesuk Yun
Sang Bae Han
Bang Yeon Hwang
Jin Tae Hong
author_facet Da Eun Hong
Ji Eun Yu
Jin Woo Lee
Dong Ju Son
Hee Pom Lee
Yuri Kim
Ju Young Chang
Dong Won Lee
Won Kyu Lee
Jaesuk Yun
Sang Bae Han
Bang Yeon Hwang
Jin Tae Hong
author_sort Da Eun Hong
collection DOAJ
description Our previous big data analyses reported a strong association between CHI3L1 expression and lung tumor development. In this present study, we investigated whether a CHI3L1-inhibiting natural compound, ebractenoid F, inhibits lung cancer cell growth and migration and induces apoptosis. Ebractenoid F concentration-dependently (0, 17, 35, 70 µM) and significantly inhibited the proliferation and migration of A549 and H460 lung cancer cells and induced apoptosis. In the mechanism study, we found that ebractenoid F bound to CHI3L1 and suppressed CHI3L1-associated AKT signaling. Combined treatment with an AKT inhibitor, LY294002, and ebractenoid F synergistically decreased the expression of CHI3L1. Moreover, the combination treatment further inhibited the growth and migration of lung cancer cells and further induced apoptosis, as well as the expression levels of apoptosis-related proteins. Thus, our data demonstrate that ebractenoid F may serve as a potential anti-lung cancer compound targeting CHI3L1-associated AKT signaling.
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spelling doaj.art-8d5da694f37a4084973015206b5b04d62023-12-02T00:42:16ZengMDPI AGMolecules1420-30492022-12-0128132910.3390/molecules28010329A Natural CHI3L1—Targeting Compound, Ebractenoid F, Inhibits Lung Cancer Cell Growth and Migration and Induces Apoptosis by Blocking CHI3L1/AKT SignalsDa Eun Hong0Ji Eun Yu1Jin Woo Lee2Dong Ju Son3Hee Pom Lee4Yuri Kim5Ju Young Chang6Dong Won Lee7Won Kyu Lee8Jaesuk Yun9Sang Bae Han10Bang Yeon Hwang11Jin Tae Hong12Medical Research Center, College of Pharmacy, Chungbuk National University, Osongsaengmyeong 1-ro, 194-21, Osong-eup, Heungduk-gu, Cheongju 28160, Republic of KoreaMedical Research Center, College of Pharmacy, Chungbuk National University, Osongsaengmyeong 1-ro, 194-21, Osong-eup, Heungduk-gu, Cheongju 28160, Republic of KoreaMedical Research Center, College of Pharmacy, Chungbuk National University, Osongsaengmyeong 1-ro, 194-21, Osong-eup, Heungduk-gu, Cheongju 28160, Republic of KoreaMedical Research Center, College of Pharmacy, Chungbuk National University, Osongsaengmyeong 1-ro, 194-21, Osong-eup, Heungduk-gu, Cheongju 28160, Republic of KoreaMedical Research Center, College of Pharmacy, Chungbuk National University, Osongsaengmyeong 1-ro, 194-21, Osong-eup, Heungduk-gu, Cheongju 28160, Republic of KoreaMedical Research Center, College of Pharmacy, Chungbuk National University, Osongsaengmyeong 1-ro, 194-21, Osong-eup, Heungduk-gu, Cheongju 28160, Republic of KoreaMedical Research Center, College of Pharmacy, Chungbuk National University, Osongsaengmyeong 1-ro, 194-21, Osong-eup, Heungduk-gu, Cheongju 28160, Republic of KoreaMedical Research Center, College of Pharmacy, Chungbuk National University, Osongsaengmyeong 1-ro, 194-21, Osong-eup, Heungduk-gu, Cheongju 28160, Republic of KoreaDepartment of New Drug Development Center, Osong Medical Innovation Foundation (KBio Health), Cheongju 28644, Republic of KoreaMedical Research Center, College of Pharmacy, Chungbuk National University, Osongsaengmyeong 1-ro, 194-21, Osong-eup, Heungduk-gu, Cheongju 28160, Republic of KoreaMedical Research Center, College of Pharmacy, Chungbuk National University, Osongsaengmyeong 1-ro, 194-21, Osong-eup, Heungduk-gu, Cheongju 28160, Republic of KoreaMedical Research Center, College of Pharmacy, Chungbuk National University, Osongsaengmyeong 1-ro, 194-21, Osong-eup, Heungduk-gu, Cheongju 28160, Republic of KoreaMedical Research Center, College of Pharmacy, Chungbuk National University, Osongsaengmyeong 1-ro, 194-21, Osong-eup, Heungduk-gu, Cheongju 28160, Republic of KoreaOur previous big data analyses reported a strong association between CHI3L1 expression and lung tumor development. In this present study, we investigated whether a CHI3L1-inhibiting natural compound, ebractenoid F, inhibits lung cancer cell growth and migration and induces apoptosis. Ebractenoid F concentration-dependently (0, 17, 35, 70 µM) and significantly inhibited the proliferation and migration of A549 and H460 lung cancer cells and induced apoptosis. In the mechanism study, we found that ebractenoid F bound to CHI3L1 and suppressed CHI3L1-associated AKT signaling. Combined treatment with an AKT inhibitor, LY294002, and ebractenoid F synergistically decreased the expression of CHI3L1. Moreover, the combination treatment further inhibited the growth and migration of lung cancer cells and further induced apoptosis, as well as the expression levels of apoptosis-related proteins. Thus, our data demonstrate that ebractenoid F may serve as a potential anti-lung cancer compound targeting CHI3L1-associated AKT signaling.https://www.mdpi.com/1420-3049/28/1/329ebractenoid FCHI3L1AKTlung cancer cell growth inhibition
spellingShingle Da Eun Hong
Ji Eun Yu
Jin Woo Lee
Dong Ju Son
Hee Pom Lee
Yuri Kim
Ju Young Chang
Dong Won Lee
Won Kyu Lee
Jaesuk Yun
Sang Bae Han
Bang Yeon Hwang
Jin Tae Hong
A Natural CHI3L1—Targeting Compound, Ebractenoid F, Inhibits Lung Cancer Cell Growth and Migration and Induces Apoptosis by Blocking CHI3L1/AKT Signals
Molecules
ebractenoid F
CHI3L1
AKT
lung cancer cell growth inhibition
title A Natural CHI3L1—Targeting Compound, Ebractenoid F, Inhibits Lung Cancer Cell Growth and Migration and Induces Apoptosis by Blocking CHI3L1/AKT Signals
title_full A Natural CHI3L1—Targeting Compound, Ebractenoid F, Inhibits Lung Cancer Cell Growth and Migration and Induces Apoptosis by Blocking CHI3L1/AKT Signals
title_fullStr A Natural CHI3L1—Targeting Compound, Ebractenoid F, Inhibits Lung Cancer Cell Growth and Migration and Induces Apoptosis by Blocking CHI3L1/AKT Signals
title_full_unstemmed A Natural CHI3L1—Targeting Compound, Ebractenoid F, Inhibits Lung Cancer Cell Growth and Migration and Induces Apoptosis by Blocking CHI3L1/AKT Signals
title_short A Natural CHI3L1—Targeting Compound, Ebractenoid F, Inhibits Lung Cancer Cell Growth and Migration and Induces Apoptosis by Blocking CHI3L1/AKT Signals
title_sort natural chi3l1 targeting compound ebractenoid f inhibits lung cancer cell growth and migration and induces apoptosis by blocking chi3l1 akt signals
topic ebractenoid F
CHI3L1
AKT
lung cancer cell growth inhibition
url https://www.mdpi.com/1420-3049/28/1/329
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