Icaritin acts synergistically with epirubicin to suppress bladder cancer growth through inhibition of autophagy.
Bladder cancer is one of the most commonly diagnosed urological malignancies. Acquired resistance to chemotherapy is a great barrier for achieving successful treatment of bladder cancer. In the present study, we investigated the effect and mechanisms of icaritin, a flavonol glycoside derived from genus Epimedium, against human bladder cancer cells. It was found that despite the low cytotoxicity in normal human HEK293 cells, icaritin significantly inhibited the proliferation and colony formation of BT5637 and T24 bladder cancer cells time- and dose-dependently compared to the DMSO vehicle control. Moreover, cell viability monitored through mitochondrial membrane potential was inhibited markedly after icaritin treatment. Further investigation indicated that icaritin may inhibit epirubicin (EPI)-induced autophagy, and acted synergistically with EPI to suppress the proliferation of BT5637 and T24 cells. These findings suggest that icaritin may prove to be a novel potent therapeutic agent for the treatment of bladder cancer.
Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Huangpu, Sanghai 200003, P.R. China.
Xiu-Wu
XW
Pan
Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Huangpu, Sanghai 200003, P.R. China.
Lin
L
Li
Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Huangpu, Sanghai 200003, P.R. China.
Yi
Y
Huang
Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Huangpu, Sanghai 200003, P.R. China.
Hai
H
Huang
The Urology Research Center of the Chinese People's Liberation Army, Changzheng Hospital, Second Military Medical University, Huangpu, Shanghai 200003, P.R. China.
Dan-Feng
DF
Xu
Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Huangpu, Sanghai 200003, P.R. China.
Yi
Y
Gao
Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Huangpu, Sanghai 200003, P.R. China.
Lu
L
Chen
Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Huangpu, Sanghai 200003, P.R. China.
Ji-Zhong
JZ
Ren
Navy No. 411 Hospital of PLA, Hongkou, Shanghai 200003, P.R. China.
Jian-Wei
JW
Cao
Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Huangpu, Sanghai 200003, P.R. China.
Yi
Y
Hong
Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Huangpu, Sanghai 200003, P.R. China.
Xin-Gang
XG
Cui
D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004357:Drug Synergism; D015251:Epirubicin / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism*
D005419:Flavonoids; D015251:Epirubicin; C499403:icaritin