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...
Main Authors: | , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2022-12-01
|
Series: | Molecules |
Subjects: | |
Online Access: | https://www.mdpi.com/1420-3049/28/1/329 |
_version_ | 1797431428303028224 |
---|---|
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. |
first_indexed | 2024-03-09T09:43:45Z |
format | Article |
id | doaj.art-8d5da694f37a4084973015206b5b04d6 |
institution | Directory Open Access Journal |
issn | 1420-3049 |
language | English |
last_indexed | 2024-03-09T09:43:45Z |
publishDate | 2022-12-01 |
publisher | MDPI AG |
record_format | Article |
series | Molecules |
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 |
work_keys_str_mv | AT daeunhong anaturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT jieunyu anaturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT jinwoolee anaturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT dongjuson anaturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT heepomlee anaturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT yurikim anaturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT juyoungchang anaturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT dongwonlee anaturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT wonkyulee anaturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT jaesukyun anaturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT sangbaehan anaturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT bangyeonhwang anaturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT jintaehong anaturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT daeunhong naturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT jieunyu naturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT jinwoolee naturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT dongjuson naturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT heepomlee naturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT yurikim naturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT juyoungchang naturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT dongwonlee naturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT wonkyulee naturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT jaesukyun naturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT sangbaehan naturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT bangyeonhwang naturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals AT jintaehong naturalchi3l1targetingcompoundebractenoidfinhibitslungcancercellgrowthandmigrationandinducesapoptosisbyblockingchi3l1aktsignals |