Quinacrine enhances cisplatin-induced cytotoxicity in four cancer cell lines.
BACKGROUND
Quinacrine has potential as a chemosensitizer when combined with chemotherapy, but its anti-cancer mechanisms remain unclear. The purpose of this study was to explore the capability of quinacrine to enhance the cytotoxic effects of cisplatin and the underlying mechanism involved.


METHODS
The potential role of quinacrine in enhancing the effects of cisplatin was investigated in Hela, SCC-VII, SACC-83 and C6 cancer cell lines with different pathologies. The inhibitory effects of quinacrine plus cisplatin on these cell lines were detected using a CCK-8 assay for viability and a TUNEL assay for apoptosis. The molecules involved in apoptotic signal translation, including cIAP-1, Bax, p53 and cleaved caspase-3, were detected by Western blot to investigate the underlying mechanism.


RESULTS
The CCK8 assay showed that quinacrine markedly enhanced the cytotoxicity of cisplatin in a dose-dependant manner in the 4 cancer cell lines. The TUNEL assay showed that treating the 4 cell lines for 24 h with cisplatin plus quinacrine significantly increased the percentage of apoptotic cells compared to treatment with single-agent treatment or untreated controls. Western blot analysis showed that quinacrine plus cisplatin significantly down-regulated cIAP-1 and up-regulated Bax and cleaved caspase-3 expression in Hela and SCC-VII cells compared with single-agent treatment.


CONCLUSIONS
Quinacrine has the potential to be used as a chemotherapy adjuvant when combined with cisplatin.
Wang
Yixiang
Y
Research Laboratory of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China.
Bi
Qingwei
Q
Dong
Ling
L
Li
Xiao
X
Ge
Xiyuan
X
Zhang
Xiaoxia
X
Fu
Jia
J
Wu
Dengcheng
D
Li
Shenglin
S
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011796:Quinacrine / Q000008:administration & dosage; D051381:Rats
D011796:Quinacrine; D002945:Cisplatin