Premium
Sclareol Enhance Susceptibility to Cisplatin in Non‐Small Cell Lung Cancer
Author(s) -
Chen Shih Yin
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1193.11
Subject(s) - cisplatin , ercc1 , lung cancer , cancer stem cell , cancer research , carboplatin , a549 cell , cancer , biology , medicine , dna repair , chemotherapy , biochemistry , nucleotide excision repair , gene
Non‐small cell lung cancer (NSCLC) is the most common type of lung cancer and hardly cured. To date, the cisplatin‐based chemotherapy has become a common clinical regimen for first‐line use in NSCLC. However, these drugs possessed some clinical side effects and toxicity as well as potential problem in drug resistance. Sclareol, a natural bioactive compound, which can significantly down‐regulation ERCC1 (Excision repair cross‐complementation group 1) protein, a well‐known DNA repair enzyme involved in the cisplatin‐resistance. Thereby, sclareol has more potential application to use as a cisplatin‐based adjuvant medicine for clinical therapy of NSCLC. In the present study. A549 cells, a human lung adenocarcinoma epithelial cell line with high expression of ERCC1 protein, and the lung cancer stem‐like cells induced by hypoxic condition were used as cell models. In A549 cell model, the regulatory effects and mechanisms of sclareol were investigated on the cell proliferation, migration, and invasion as well as ERCC1 expression. On the other hand, the possible effects and activities of sclareol were evaluated whether it can reduce the generation, proliferation, differentiation, migration and invasion of cancer stem cells in the hypoxic condition‐induced cancer stem‐like cells. Cobalt chloride was used to treat A549 cells for 48 hours to induce overexpression of cancer stem cell markers (CD90/CD133). Our results showed that cisplatin‐induced cytotoxicity against lung cancer stem‐like cells is less than that against A549 cells. Yet the combination use of cisplatin and sclareol demonstrated a significant suppression on the survival rate of A549 cells and lung cancer stem‐like cells. In addition, the combination use of cisplatin and sclareol can significantly inhibit cell migration by more than 20% as compared to cisplatin use alone. We further analyzed the differential expression levels of cisplatin‐resistance related molecules and its upstream molecules (ERCC1, Snail, AKT and ERK) by the sclareol treatment. Our results showed that sclareol treatment can down‐regulated ERCC1 and its upstream molecules. Our data demonstrated that sclareol can significantly down‐regulate drug‐resistance associated proteins and its upstream molecules (ERCC1, Snail, AKT and ERK), and thus enhanced the cytotoxic effects of cisplatin on A549 cells and lung cancer stem‐like cells. Thereby, sclareol can be potentially applied as the cisplatin‐based adjuvant for clinical therapy for NSCLC. Support or Funding InformationExperimental Flow