Renshu Zhang

Vitamin E Succinate Induces Ceramide-Mediated Apoptosis in Head and Neck Squamous Cell Carcinoma In vitro and In vivo

Purpose: Vitamin E succinate (α-TOS) inhibits the growth of cancer cells without unacceptable side effects. Therefore, the mechanisms associated with the anticancer action of α-TOS, including ceramide-mediated apoptosis, were investigated using head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo. Experimental Design: Five different human HNSCC cell lines (JHU-011, JHU-013, JHU-019, JHU-022, and JHU-029) were treated with α-TOS, and its effects on cell proliferation, cell cycle progression, ceramide-mediated apoptosis, and ceramide metabolism were evaluated. The anticancer effect of α-TOS was also examined on JHU-022 solid tumor xenograft growth in immunodeficient mice. Results: α-TOS inhibited the growth of all the HNSCC cell lines in vitro in a dose- and time-dependent manner. Thus, JHU-013 and JHU-022 cell lines were more sensitive to α-TOS than the other cell lines. Cellular levels of ceramide, sphingomyelinase activity, caspase-3, and p53 were elevated with increasing time of exposure to α-TOS. The degradation of poly(ADP-ribose) polymerase protein in JHU-022 cells treated with α-TOS provided evidence for apoptosis. The amounts of nuclear factor κB, Bcl-2, and Bcl-XL proteins were reduced in the cells treated with α-TOS for 6 hours. The levels of caspase-9, murine double minute-2, and IκB-α proteins were unchanged after α-TOS treatment. I.p. administration of α-TOS slowed tumor growth in immunodeficient mice. Conclusions: α-TOS showed promising anticancer effects to inhibit HNSCC growth and viability in vivo and in vitro. The induction of enzymes involved in ceramide metabolism by α-TOS suggests that ceramide-mediated apoptosis may expand therapeutic strategies in the treatment of carcinoma.

Visualizing Head and Neck Tumors In Vivo Using Near- Infrared Fluorescent Transferrin Conjugate

Transferrin receptor (TfR) is overexpressed in human head and neck squamous cell carcinomas (HNSCCs). This study was carried out to investigate the feasibility of imaging HNSCC by targeting TfR using near-infrared fluorescent transferrin conjugate (TfNIR). Western blot analysis of four HNSCC cell lines revealed overexpression of TfR in all four lines compared with that in normal keratinocytes (OKFL). Immunocytochemistry further confirmed the expression of TfR and endocytosis of TfNIR in JHU-013 culture cells. Following intravenous administration of TfNIR (200 μL, 0.625 μg/μL), fluorescent signal was preferentially accumulated in JHU-013 tumor xenografts grown in the lower back (n = 14) and oral base tissues (n = 4) of nude mice. The signal in tumors was clearly detectable as early as 10 minutes and reached the maximum at 90 to 120 minutes postinjection. The background showed an increase, followed by a decrease at a much faster pace than tumor signal. A high fluorescent ratio of the tumor to muscle was obtained (from 1.42 to 4.15 among tumors), usually achieved within 6 hours, and correlated with the tumor size (r = .74, p = .002). Our results indicate that TfR is a promising target and that TfNIR-based optical imaging is potentially useful for noninvasive detection of early HNSCC in the clinic.

Relationship Between Aerobic Fitness, the Serum IGF-1 Profiles of Healthy Young Adult African American Males, and Growth of Prostate Cancer Cells

The growth of prostate tumors is mediated by the bioavailability of androgens and insulin-like growth factors. This study tested the hypothesis that healthy young adult African American men exhibiting low aerobic capacity (fitness) have serum insulin-like growth Factor-1 (IGF-1) and testosterone levels that promote growth of prostate cancer cells. A cross-sectional data research design was used to study groups of 18- to 26-year-old healthy men exhibiting low and moderate aerobic fitness, based on their peak oxygen consumption (VO2peak). The individual serum levels of IGF-1, IGF-1 binding protein-3 (IGFBP-3), and testosterone were measured. In vitro growth of androgen-dependent LNCaP prostate tumor cells was measured after incubation in culture medium fortified with each subject’s serum. Aerobic capacity was significantly greater in the moderate-fitness group than in the low-fitness group without an intergroup difference in body mass index. The serum IGF-1 concentration was significantly higher in the low-fitness group in the absence of an intergroup difference in serum testosterone. The serum IGFBP-3 concentration was significantly lower in the low-fitness group. Prostate tumor cell growth was significantly greater in the cultures incubated in media containing the sera of the low-fitness group than in the sera of the moderate-fitness group. These findings suggest that moderate aerobic fitness in young adults may decrease the circulating levels of free IGF-1 and lower the potential to support growth of prostate cancer cells.