Synergistic inhibitory effect of α-humulene and sclareol on human pancreatic cancer cells

Both α-Humulene (HUM) and sclareol (SCL) are naturally occurred compounds and have been shown to exert anti-inflammatory and anticancer activities. The effects of these two compounds alone or in combination on pancreatic cancer cells have not been reported. In the present study, we investigated the...

Full description

Bibliographic Details
Main Authors: Yu Kang, Xiao Wang, Xingchuan Wei, Dongli Li, Lishe Gan, Jingwei Jin, Rihui Wu, Panpan Wu, Zhaojun Sheng, Kun Zhang, Susan Goodin, Xuetao Xu, Xi Zheng
Format: Article
Language:English
Published: Elsevier 2022-02-01
Series:Journal of Functional Foods
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1756464622000287
_version_ 1819291681449574400
author Yu Kang
Xiao Wang
Xingchuan Wei
Dongli Li
Lishe Gan
Jingwei Jin
Rihui Wu
Panpan Wu
Zhaojun Sheng
Kun Zhang
Susan Goodin
Xuetao Xu
Xi Zheng
author_facet Yu Kang
Xiao Wang
Xingchuan Wei
Dongli Li
Lishe Gan
Jingwei Jin
Rihui Wu
Panpan Wu
Zhaojun Sheng
Kun Zhang
Susan Goodin
Xuetao Xu
Xi Zheng
author_sort Yu Kang
collection DOAJ
description Both α-Humulene (HUM) and sclareol (SCL) are naturally occurred compounds and have been shown to exert anti-inflammatory and anticancer activities. The effects of these two compounds alone or in combination on pancreatic cancer cells have not been reported. In the present study, we investigated the effects of HUM and SCL on human pancreatic cancer cells cultured in vitro and grown as xenograft tumors in vivo. In the in vitro studies, we found that HUM and SCL in combination synergistically inhibited the growth of pancreatic cancer cells. The combination strongly stimulated apoptosis, and suppressed migration, invasion and sphere formation in pancreatic cells. Studies on the mechanism of action showed that the combination strongly decreased the levels of NF-κB, phosphor Akt (pAkt) and Bcl-2, and increased the level of Bax. Knockdown of NF-κB and Akt by small interfering RNA (siRNA) abrogated the inhibitory effect of HUM and SCL on pancreatic cancer cells. The in vivo study showed that HUM and SCL in combination suppressed the growth of Panc-1 xenograft tumors in immunodeficient mice. Results of the present study indicate that HUM and SCL in combination may represent an effective approach for inhibiting the growth of pancreatic cancer.
first_indexed 2024-12-24T03:42:30Z
format Article
id doaj.art-f7ef0a582a154f18954b8f73b8a23a4b
institution Directory Open Access Journal
issn 1756-4646
language English
last_indexed 2024-12-24T03:42:30Z
publishDate 2022-02-01
publisher Elsevier
record_format Article
series Journal of Functional Foods
spelling doaj.art-f7ef0a582a154f18954b8f73b8a23a4b2022-12-21T17:16:52ZengElsevierJournal of Functional Foods1756-46462022-02-0189104958Synergistic inhibitory effect of α-humulene and sclareol on human pancreatic cancer cellsYu Kang0Xiao Wang1Xingchuan Wei2Dongli Li3Lishe Gan4Jingwei Jin5Rihui Wu6Panpan Wu7Zhaojun Sheng8Kun Zhang9Susan Goodin10Xuetao Xu11Xi Zheng12School of Biotechnology and Health Sciences, Wuyi University, Jiangmen City, Guangdong Province 529020, ChinaSchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen City, Guangdong Province 529020, ChinaDepartment of Chemistry and Chemical Engineering, Guangzhou University, Guangzhou 510006, ChinaSchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen City, Guangdong Province 529020, China; International Healthcare Innovation Institute (Jiangmen), Jiangmen City, Guangdong Province 529020, ChinaSchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen City, Guangdong Province 529020, China; International Healthcare Innovation Institute (Jiangmen), Jiangmen City, Guangdong Province 529020, ChinaSchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen City, Guangdong Province 529020, ChinaSchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen City, Guangdong Province 529020, ChinaSchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen City, Guangdong Province 529020, ChinaSchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen City, Guangdong Province 529020, ChinaSchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen City, Guangdong Province 529020, ChinaRutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USASchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen City, Guangdong Province 529020, China; Corresponding authors.Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Corresponding authors.Both α-Humulene (HUM) and sclareol (SCL) are naturally occurred compounds and have been shown to exert anti-inflammatory and anticancer activities. The effects of these two compounds alone or in combination on pancreatic cancer cells have not been reported. In the present study, we investigated the effects of HUM and SCL on human pancreatic cancer cells cultured in vitro and grown as xenograft tumors in vivo. In the in vitro studies, we found that HUM and SCL in combination synergistically inhibited the growth of pancreatic cancer cells. The combination strongly stimulated apoptosis, and suppressed migration, invasion and sphere formation in pancreatic cells. Studies on the mechanism of action showed that the combination strongly decreased the levels of NF-κB, phosphor Akt (pAkt) and Bcl-2, and increased the level of Bax. Knockdown of NF-κB and Akt by small interfering RNA (siRNA) abrogated the inhibitory effect of HUM and SCL on pancreatic cancer cells. The in vivo study showed that HUM and SCL in combination suppressed the growth of Panc-1 xenograft tumors in immunodeficient mice. Results of the present study indicate that HUM and SCL in combination may represent an effective approach for inhibiting the growth of pancreatic cancer.http://www.sciencedirect.com/science/article/pii/S1756464622000287α-HumuleneSclareolPancreatic cancerApoptosisMigrationInvasion
spellingShingle Yu Kang
Xiao Wang
Xingchuan Wei
Dongli Li
Lishe Gan
Jingwei Jin
Rihui Wu
Panpan Wu
Zhaojun Sheng
Kun Zhang
Susan Goodin
Xuetao Xu
Xi Zheng
Synergistic inhibitory effect of α-humulene and sclareol on human pancreatic cancer cells
Journal of Functional Foods
α-Humulene
Sclareol
Pancreatic cancer
Apoptosis
Migration
Invasion
title Synergistic inhibitory effect of α-humulene and sclareol on human pancreatic cancer cells
title_full Synergistic inhibitory effect of α-humulene and sclareol on human pancreatic cancer cells
title_fullStr Synergistic inhibitory effect of α-humulene and sclareol on human pancreatic cancer cells
title_full_unstemmed Synergistic inhibitory effect of α-humulene and sclareol on human pancreatic cancer cells
title_short Synergistic inhibitory effect of α-humulene and sclareol on human pancreatic cancer cells
title_sort synergistic inhibitory effect of α humulene and sclareol on human pancreatic cancer cells
topic α-Humulene
Sclareol
Pancreatic cancer
Apoptosis
Migration
Invasion
url http://www.sciencedirect.com/science/article/pii/S1756464622000287
work_keys_str_mv AT yukang synergisticinhibitoryeffectofahumuleneandsclareolonhumanpancreaticcancercells
AT xiaowang synergisticinhibitoryeffectofahumuleneandsclareolonhumanpancreaticcancercells
AT xingchuanwei synergisticinhibitoryeffectofahumuleneandsclareolonhumanpancreaticcancercells
AT donglili synergisticinhibitoryeffectofahumuleneandsclareolonhumanpancreaticcancercells
AT lishegan synergisticinhibitoryeffectofahumuleneandsclareolonhumanpancreaticcancercells
AT jingweijin synergisticinhibitoryeffectofahumuleneandsclareolonhumanpancreaticcancercells
AT rihuiwu synergisticinhibitoryeffectofahumuleneandsclareolonhumanpancreaticcancercells
AT panpanwu synergisticinhibitoryeffectofahumuleneandsclareolonhumanpancreaticcancercells
AT zhaojunsheng synergisticinhibitoryeffectofahumuleneandsclareolonhumanpancreaticcancercells
AT kunzhang synergisticinhibitoryeffectofahumuleneandsclareolonhumanpancreaticcancercells
AT susangoodin synergisticinhibitoryeffectofahumuleneandsclareolonhumanpancreaticcancercells
AT xuetaoxu synergisticinhibitoryeffectofahumuleneandsclareolonhumanpancreaticcancercells
AT xizheng synergisticinhibitoryeffectofahumuleneandsclareolonhumanpancreaticcancercells