Icaritin acts synergistically with epirubicin to suppress bladder cancer growth through inhibition of autophagy

Abstract

Abstract. 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.

Epirubicin suppresses proliferative and metastatic potential by downregulating transforming growth factor‐β‐induced expression in urothelial carcinoma

“…Routine intravesical instillation with EPI has been widely performed to reduce the recurrence of UC following TUR. Although EPI chemotherapy has achieved an average 16 months of mean disease‐free survival, and suppressed the progression and recurrence in patients with non‐muscle‐invasive UC, acquired resistance to EPI is still a barrier to achieving successful treatment of UC . Some studies with combination treatments have shown antitumor drug action and possible synergistic effects against UC.…”

“…Some studies with combination treatments have shown antitumor drug action and possible synergistic effects against UC. Ciprofloxacin has been shown to synergistically increase EPI‐induced apoptosis in UC cell lines, and icaritin acts synergistically with EPI to suppress UC cell growth through inhibition of autophagy . However, the molecular mechanisms of EPI in UC remain unclear.…”

Anticancer effect of salidroside reduces viability through autophagy/PI3K/Akt and MMP‑9 signaling pathways in human bladder cancer cells

“…Autophagy is a normal and ubiquitous physiological process that represents an active defensive strategy for external pessimal stimulation (8); it is also an important form of programmed cell death. Autophagy additionally participates in the pathological development of multiple diseases, including malignant tumor types (27).…”

“…Under normal physiological conditions, autophagy is beneficial in maintaining a self-stabilized state (8). When there is stress, autophagy may prevent the accumulation of toxic or carcinogenic proteins and organelles and inhibit cellular cancerization (9).…”

“…When there is stress, autophagy may prevent the accumulation of toxic or carcinogenic proteins and organelles and inhibit cellular cancerization (9). However, a number of previous studies have indicated that, following neoplasia, autophagy may provide more abundant nutrition for cancer cells and promote tumor growth (8,9). Therefore, in the process of tumorigenesis and tumor development, autophagy serves an important function.…”