• Korean Journal of Pharmacognosy
• /
• v.32 no.2 s.125
• /
• pp.163-167
• /
• 2001

Prunella vulgaris L. aqua-acupuncture solution (PVAS) was tested for cancer chemopreventive activity using chemoprevention-associated biochemical end points. The following effects were measured. : (a) inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced cytochrome P4501A1 activity (b) inhibition of $[^3H]B[a]P-DNA$ binding (c) inhibition of phorbol 12-myristate 13-acetate (TPA)-induced free radical formation in HL-60 cells (d) inhibition of polyamine metabolism. PVAS inhibited cytochrome P4501A1-mediated ethoxyresorufin-O-deethylase activity. The binding of $[^3H]B[a]P$ metabolites to DNA of NCTC-clone 1469 cells was inhibited significantly by PVAS. There is 22% inhibition of TPA-induced free radical formation in human leukemic cells with 5 mg/ml PVAS. Proliferation of Acanthamoeba castellanii was inhibited by PAVS at concentration of 30 mg/ml. PAVS positive in these assays may inhibit the carcinogenesis process and is considered very promising cancer-preventing agent because of its multiple activities.

• Nutrition Research and Practice
• /
• v.7 no.6
• /
• pp.439-445
• /
• 2013

It has been shown that dysregulation of IGF-1 signaling is associated with tumor incidence and progression, whereas blockade of the signaling can effectively inhibit carcinogenesis. Although several mechanisms of anticancer activity of quercetin were proposed, molecular targets of quercetin have not been identified yet. Hence, we assessed the effect of quercetin on IGF-1 signaling inhibition in BK5.IGF-1 transgenic (Tg) mice, which over-expresses IGF-1 in the skin epidermis. A quercetin diet (0.02% wt/wt) for 20 weeks remarkably delayed the incidence of skin tumor by 2 weeks and reduced tumor multiplicity by 35% in a 7,12-dimethylbenz(a)anthracene (DMBA)-tetradecanoyl phorbol-13-acetate (TPA) two stage mouse skin carcinogenesis protocol. Moreover, skin hyperplasia in Tg mice was significantly inhibited by a quercetin supplementation. Further analysis of the MT1/2 skin papilloma cell line showed that a quercetin treatment dose dependently suppressed IGF-1 induced phosphorylation of the IGF-1 receptor (IGF-1R), insulin receptor substrate (IRS)-1, Akt and S6K; however, had no effect on the phosphorylation of PTEN. Additionally, the quercetin treatment inhibited IGF-1 stimulated cell proliferation in a dose dependent manner. Taken together, these data suggest that quercetin has a potent anticancer activity through the inhibition of IGF-1 signaling.

• Molecules and Cells
• /
• v.39 no.3
• /
• pp.266-279
• /
• 2016

The mechanism by which 12-O-tetradecanoylphorbol-13-acetate (TPA) bypasses cellular senescence was investigated using human diploid fibroblast (HDF) cell replicative senescence as a model. Upon TPA treatment, protein kinase C (PKC) ${\alpha}$ and $PKC{\beta}1$ exerted differential effects on the nuclear translocation of cytoplasmic pErk1/2, a protein which maintains senescence. $PKC{\alpha}$ accompanied pErk1/2 to the nucleus after freeing it from $PEA-15pS^{104}$ via $PKC{\beta}1$ and then was rapidly ubiquitinated and degraded within the nucleus. Mitogen-activated protein kinase docking motif and kinase activity of $PKC{\alpha}$ were both required for pErk1/2 transport to the nucleus. Repetitive exposure of mouse skin to TPA downregulated $PKC{\alpha}$ expression and increased epidermal and hair follicle cell proliferation. Thus, $PKC{\alpha}$ downregulation is accompanied by in vivo cell proliferation, as evidenced in 7, 12-dimethylbenz(a)anthracene (DMBA)-TPA-mediated carcinogenesis. The ability of TPA to reverse senescence was further demonstrated in old HDF cells using RNA-sequencing analyses in which TPA-induced nuclear $PKC{\alpha}$ degradation freed nuclear pErk1/2 to induce cell proliferation and facilitated the recovery of mitochondrial energy metabolism. Our data indicate that TPA-induced senescence reversal and carcinogenesis promotion share the same molecular pathway. Loss of $PKC{\alpha}$ expression following TPA treatment reduces pErk1/2-activated SP1 biding to the $p21^{WAF1}$ gene promoter, thus preventing senescence onset and overcoming G1/S cell cycle arrest in senescent cells.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.4
• /
• pp.2301-2305
• /
• 2013

Ardisia crispa (Family: Myrsinaceae) is an evergreen, fruiting shrub that has been traditionally used as folklore medicine. Despite a scarcity of research publications, we have succeeded in showing suppressive effects on murine skin papillomagenesis. In extension, the present research was aimed at determining the effect of a quinone-rich fraction (QRF) isolated from the same root hexane extract on both initiation and promotion stages of carcinogenesis, at the selected dose of 30 mg/kg. Mice (groups I-IV) were initiated with a single dose of 7,12-dimethylbenz(${\alpha}$)anthracene (DMBA, $100{\mu}g/100{\mu}l$) followed by repeated promotion of croton oil (1%) twice weekly for 20 weeks. In addition, group I (anti-initiation) received QRF 7 days before and after DMBA; group II (anti-promotion) received QRF 30 minutes before each croton oil application; group III (anti-initiation/promotion) was treated with QRF as a combination of group I and II. A further two groups served as vehicle control (group V) and treated control (group VI). As carcinogen control, group IV showed the highest tumor volume ($8.79{\pm}5.44$) and tumor burden ($3.60{\pm}1.17$). Comparatively, group III revealed only 20% of tumor incidence, tumor burden ($3.00{\pm}1.00$) and tumor volume ($2.40{\pm}1.12$), which were significantly different from group IV. Group II also showed significant reduction of tumor volume (3.11), tumor burden (3.00) and tumor incidence (11.11%), along with prominent increase of latency period of tumor formation (week 12). Group I, nonetheless, demonstrated marked increment of tumor incidence by 40% with prompted latency period of tumor formation (week 7). No tumor formation was observed in groups V and VI. This study provided clear evidence of inhibitory effects of QRF during promotion period which was in agreement with our previous findings. The mechanism(s) underlying such effects have yet to be elucidated.

• Proceedings of the Korea Electromagnetic Engineering Society Conference
• /
• 1999.07a
• /
• pp.173-186
• /
• 1999

Several epidemiological studies have suggested that residential or occupational exposure to power frequency magnetic fields (MF) might increase the risk of cancer. The objective of this study is to elucidate the possible carcinogenic effects of MF exposure using female Sprague-Dawley (Crj:CD)rats. A total of 360rats was randomly divided into 6 groups of 60 rats each. Two groups were served as a negative control (vehicle: sesame oil only) or a positive control (single oral administration of 7, 12dimethylbenz(a)anthracene; DMBA, 90mg/kg body weight at 50-52days of age). Other four groups were simultaneously exposed to 0 (sham-exposed) 7, 70 or 350 $\mu$T(rms), continuous circularly polarized 50HzMF, 22 hrs/day, 7 days/weeks for 30weeks from 8weeks of age. Experiment was conducted under SPF condition and in a blinded manner, Ten animals in each grout were served as satellite animals and their several hormonal concentrations in sera, such as melatonin and prolactin, collected at the midnight were measured. In addition, complete histopathological examination were performed in other 50 animals per each group. In the positive control group, the first mammary nodule was palpated at the 7th weeks of experiment in 5 out of 59 animals. Afterward, the incidence of palpable mammary nodules increased steadily and reached at 76% and 98% of live animals at 14weeks and the end of experiment in sham and 350$\mu$ T-exposed groups were not significantly different from those in the sham-exposed and negative control groups. Histopathologocally, most of palpable nodules were mammary tumors. The incidences of animals with mammary tumors per animals survived ant the end of experiment were 4.1 and 100% in the negative and positive control groups, and 0.0, 6.0, 8.0 and 6.0% in the sham-, 7, 70and 350 $\mu$T-exposed groups, respectively. These incidences in three MF-exposed groups were not significantly different from those in both the sham- exposed and negative control groups. Based on these results, it was not supported that continuous circularly polarized 50 Hz magnetic fields at up to 350$\mu$T affect the incidence of spontaneous mammary tumors in female SD rats under the present experimental conditions.