title: Gingerol Reverses the Cancer-Promoting Effect of Capsaicin by Increased TRPV1 Level in a Urethane-Induced Lung Carcinogenic Model.
abstract: Both gingerol and capsaicin are agonists of TRPV1, which can negatively control tumor progression. This study observed the long-term effects of oral administration of 6-gingerol alone or in combination with capsaicin for 20 weeks in a urethane-induced lung carcinogenic model. We showed that lung carcinoma incidence and multiplicity were 70% and 21.2 ± 3.6, respectively, in the control versus 100% and 35.6 ± 5.2 in the capsaicin group (P < 0.01) and 50% and 10.8 ± 3.1 in the 6-gingerol group (P < 0.01). The combination of 6-gingerol and capsaicin reversed the cancer-promoting effect of capsaicin (carcinoma incidence of 100% versus 20% and multiplicity of 35.6 ± 5.2 versus 4.7 ± 2.3; P < 0.001). The cancer-promoting effect of capsaicin was due to increased epidermal growth-factor receptor (EGFR) level by decreased transient receptor potential vanilloid type-1 (TRPV1) level (P < 0.01) . The capsaicin-decreased EGFR level subsequently reduced levels of nuclear factor-κB (NF-κB) and cyclin D1 that favored enhanced lung epithelial proliferation and epithelial-mesenchymal transition (EMT) during lung carcinogenesis (P < 0.01). In contrast, 6-gingerol promoted TRPV1 level and drastically decreased the levels of EGFR, NF-κB, and cyclin D1 that favored reduced lung epithelial proliferation and EMT (P < 0.01). This study provides valuable information for the long-term consumption of chili-pepper-rich diets to decrease the risk of cancer development.
authors.affiliation: Institute of Pharmacy, Pharmacy College of Henan University , Jinming District, Kaifeng, Henan 475004, China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Geng
authors.affiliation: Institute of Pharmacy, Pharmacy College of Henan University , Jinming District, Kaifeng, Henan 475004, China.
authors.forename: Yaqiu
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Institute of Pharmacy, Pharmacy College of Henan University , Jinming District, Kaifeng, Henan 475004, China.
authors.forename: Mingjing
authors.initials: M
authors.lastname: Meng
authors.affiliation: Institute of Pharmacy, Pharmacy College of Henan University , Jinming District, Kaifeng, Henan 475004, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Institute of Pharmacy, Pharmacy College of Henan University , Jinming District, Kaifeng, Henan 475004, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Cao
authors.affiliation: Institute of Pharmacy, Pharmacy College of Henan University , Jinming District, Kaifeng, Henan 475004, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Ma
authors.affiliation: Institute of Pharmacy, Pharmacy College of Henan University , Jinming District, Kaifeng, Henan 475004, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Du
authors.affiliation: Institute of Pharmacy, Pharmacy College of Henan University , Jinming District, Kaifeng, Henan 475004, China.
authors.forename: Jiahuan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Oncology, The First Hospital Affiliated to Henan University , Kaifeng, Henan 475001, China.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Duan
authors.affiliation: Institute of Pharmacy, Pharmacy College of Henan University , Jinming District, Kaifeng, Henan 475004, China.
authors.forename: Gangjun
authors.initials: G
authors.lastname: Du
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage / Q000009:adverse effects*; D063646:Carcinogenesis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002396:Catechols / Q000008:administration & dosage*; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005233:Fatty Alcohols / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D014520:Urethane / Q000633:toxicity*
chemical_list: D002396:Catechols; D005233:Fatty Alcohols; D016328:NF-kappa B; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D014520:Urethane; C007845:gingerol; D066246:ErbB Receptors; D002211:Capsaicin
keywords: 6-gingerol; NF-κB level; TRPV1 level; capsaicin; lung carcinogenesis