icaritin and Mouth-Neoplasms

Icaritin can inhibit cell proliferation and induce apoptosis in Oral Squamous Cell Carcinoma (OSCC). However, low solubility limits its clinical usage.. To improve the efficacy of icaritin treatment, a micelle system was designed for targeted delivery of drugs to OSCC cells.. In the present study, the micelles loaded with icaritin were self-assembled from the amphipathic polymer via film dispersion. Nanoparticles were characterized with the transmission electron microscope and dynamic light scattering. The cytotoxicity of icaritin nanoparticles was analyzed by CCK-8, and in vitro target-selective intracellular uptake behaviors were observed using a laser confocal microscope.. The micelles were spherical with the mean diameter of 121.2 nm. in vitro studies revealed that icaritin was stablely and slowly released from micelles. Cytotoxicity analysis demonstrated that icartin-loaded micelles exhibited better therapeutic efficacy compared with free icaritin. Cellular uptake and intracellular release results revealed that micelles efficiently delivered icaritin into OSCC cells.. These results suggest that encapsulated icaritin in polycaprolactone - polyethylene glycol (PCL-PEG) micelles may provide safe and effective drug delivery in OSCC treatments.

Topics: Carcinoma, Squamous Cell; Drug Carriers; Flavonoids; Head and Neck Neoplasms; Humans; Micelles; Mouth Neoplasms; Polyesters; Polyethylene Glycols; Squamous Cell Carcinoma of Head and Neck

The present study is aimed to investigate the apoptosis-inducing effect of icaritin in human oral squamous cell carcinoma (OSCC) cells and the associated mechanisms.. KB and SCC9 cell lines were used as model cell lines. Effect of icaritin on apoptosis was analyzed by flow cytometry. The effect of icaritin on mitochondrial apoptotic pathway was demonstrated by loss of mitochondrial membrane potential and release of cytocrome C from mitochondria. MiR-124 mimic and miR-124 inhibitor were used to manipulate the expression of miR-124 in OSCC cells. SiRNA targeting Sp1 and DNMT1 as well as Sp1 and DNMT1 overexpressing vector were utilized to confirm their roles in the apoptosis-inducing effect of icaritin in OSCC cells. Activation of relevant signaling pathway by icaritin and effect of icaritin on expression of targeting molecules were determined by western blots or qRT-PCR.. Our results showed that icaritin inhibited tumor cell viability in a dose- and time-dependent manner, and induced cell apoptosis via intrinsic mitochondrial pathway by upregulating miR-124. Moreover, our results showed that the icaritin exerted regulatory effect on miR-124 through suppressing Sp1/DNMT1 signaling.. Our data provide the first experimental evidence that icaritin induces mitochondrial apoptosis in OSCC cells by upregulating miR-124 and suggest a new mechanism to explain its anti-tumor effects.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Survival; Cytochromes c; DNA (Cytosine-5-)-Methyltransferase 1; DNA (Cytosine-5-)-Methyltransferases; Dose-Response Relationship, Drug; Flavonoids; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Membrane Potential, Mitochondrial; MicroRNAs; Mitochondria; Mouth Neoplasms; RNA Interference; Signal Transduction; Sp1 Transcription Factor; Squamous Cell Carcinoma of Head and Neck; Time Factors; Transfection; Up-Regulation

Icaritin, a traditional Chinese medicine, possesses antitumor activity. The current study aimed to investigate icaritin effect and potential mechanism on oral squamous cell carcinoma (OSCC) development. OSCC cells proliferation, apoptosis, and autophagy were analyzed after incubation with icaritin at different concentrations and incubation times. The expressions of proteins related to proliferation, apoptosis, and autophagy, as well as signal transducer and activator of transcription 3 (STAT3) signal network, were also evaluated by western blot. Furthermore, STAT3 was knocked down by siRNA transfection to determine STAT3 role in OSCC cell proliferation and apoptosis. An oral specific carcinogenesis mouse model was used to explore icaritin effect on OSCC in vivo. Icaritin significantly inhibited OSCC proliferation in vitro and reduced the expression of both the cell-cycle progression proteins cyclin A2 and cyclin D1. Besides, icaritin increased cleaved caspase 3 and cleaved poly-(ADP-ribose) polymerase expression leading to apoptosis, and it activated autophagy. Icaritin significantly inhibited the expression of phospho-STAT3 (p-STAT3) in a dose- and time-dependent manner. In the in vivo experiment, the number of malignant tumors in the icaritin-treated group was significantly lower than the control. Overall, icaritin suppressed proliferation, promoted apoptosis and autophagy, and inhibited STAT3 signaling in OSCC in vitro and in vivo. In conclusion, icaritin might be a potential therapeutic agent against OSCC development.

Topics: Animals; Apoptosis; Autophagy; Blotting, Western; Carcinoma, Squamous Cell; Caspase 3; Cell Line, Tumor; Cell Proliferation; Cyclins; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Flavonoids; Humans; Mice, Inbred C57BL; Mouth Neoplasms; Phosphorylation; Poly(ADP-ribose) Polymerases; RNA Interference; Signal Transduction; STAT3 Transcription Factor; Time Factors