• Journal of Life Science
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• v.28 no.4
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• pp.465-471
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• 2018

Bee pollen is one of many types of alternative remedies, and it has been used for a long time throughout the world. It has numerous health effects, including antifungal, antibacterial, and antioxidant properties, immune modulation, enhanced cell proliferation, and even anti-carcinogenic effects. This study was designed to elucidate the effects of bee pollen on benign prostatic hyperplasia in rodents. For this experiment, we used nano-sized bee pollen produced through wet-grinding technology, thereby the extraction efficiency of the active ingredients in the bee pollen was significantly enhanced. First, We found that nano-sized bee pollen significantly reduced the size of prostates enlarged by chronic testosterone administration. In addition, nano-sized bee pollen significantly reduced the plasma concentration of the prostate-specific antigen (PSA). Interestingly, nano-sized bee pollen did not reduce the testosterone-induced increase in the plasma concentration of prostaglandin $E_2$ ($PGE_2$). The beneficial effects of nano-sized bee pollen in reducing both the size of the prostate and the plasma concentration of PSA was comparable to that of dutasteride. Finally, nano-sized bee pollen did not cause damage in LNCaP cells which are androgen-sensitive human prostate adenocarcinoma cells. Together, these data indicate that nano-sized bee pollen may be able to be used as a good alternative remedy for the treatment of benign prostatic hyperplasia.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.8
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• pp.1119-1125
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• 2010

To evaluate resveratrol as a prostate cancer preventive material, we investigated its anti-proliferative and apoptotic effects in RC-58T/h/SA#4 primary human prostate cancer cells. Resveratrol significantly decreased the number of viable RC-58T/h/SA#4 cells in a dose- and time-dependent manner. Resveratrol showed cytotoxicity against RC-58T/h/SA#4, LNCaP, PC-3 human prostate cancer cells with $IC_{50}$ values of 245, 320 and $340\;{\mu}M$, respectively. However the cytotoxic potential of resveratrol against normal RWPE-1 cells was lower ($IC_{50}=982\;{\mu}M$). Resveratrol induced cell death as evidenced by the increased formation of apoptotic bodies, nuclear condensation, sub-G1 phase, and DNA fragmentation. Resveratrol activated initiator caspases 8, and 9 as well as effector caspase 3 in a dose-dependent manner. Furthermore, the general caspase inhibitor z-VAD-fmk significantly inhibited resveratrol-induced apoptosis compared to cells without treatment. These results clearly indicate that resveratrol-induced apoptosis was dependent on caspase activation. Further, resveratrol modulated the down regulation of Bcl-2 (anti-apoptotic), and Bid. However, the level of Bax (pro-apoptotic) remained unchanged. These results suggest that resveratrol induced apoptosis in RC-58T/h/SA#4 cells via a mitochondrial-mediated caspase-dependent pathway, suggesting therapeutic potential against prostate cancer.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.2
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• pp.318-322
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• 2014

5-Alpha reductase II, which converts testosterone (T) to dihydrotestosterone (DHT), is a crucial enzyme II in benign prostatic hyperplasia. Inhibitory effects of Curcuma longa L. (CL) extracts on 5-alpha reductase II activity were investigated in rat prostate tissue homogenates as well as LNCaP cells expressing human 5-alpha reductase II. Hot water extract (CL-HW) of Curcuma longa L. significantly inhibited 5-alpha reductase activity by over 80% at a concentration of $100{\mu}g/mL$, whereas 20% ethanol extracts (CL-E20) of Curcuma longa L. exhibited significant inhibitory activity from $50{\mu}g/mL$. These results indicated that Curcuma longa L is a potent 5-alpha reductase II inhibitor for benign prostatic hyperplasia treatment.

• The Korean Journal of Food And Nutrition
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• v.25 no.2
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• pp.259-265
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• 2012

In this study, we determined total polyphenol content(TPC) and total flavonoid content(TFC) of extracts from Korean cabbage and cabbage using a spectrophotometric method as well as glucosinolates concentration by HPLC. TPCs of Korean cabbage and cabbage extracts were 308.48 ${\mu}g$ GAE/g dry weight and 344.75 ${\mu}g$ GAE/g dry weight, respectively. TFCs of Korean cabbage and cabbage extracts were 5.33 ${\mu}g$ QE/g dry weight and 5.95 ${\mu}g$ QE/g dry weight, respectively. We found six different glucosinolates, namely progoitrin, glucoalyssin, gluconapin, glucobrassicanapin, glucobrassicin and 4-methoxyglucobrassicin in the Korean cabbage extract. In the cabbage extract, there was four glucosinolates, namely glucoraphanin, sinigrin, glucobrassicin and 4-methoxyglucobrassicin. We determined the cytotoxic effect of Korean cabbage and cabbage extracts in AGS human stomach cancer cells, HepG2 human hepatic cancer cells and LNCaP human prostate cancer cells by MTT assay. Dose-dependent relationships were found between the extract concentrations and cancer cell growth inhibition. The overall results support that both Korean cabbage and cabbage, the major vegetables in Korea, contain bioactive compounds such as polypheol, flavonoids as well as glucosinolates and they may play a positive role in cancer prevention.

• Journal of Life Science
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• v.19 no.7
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• pp.892-898
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• 2009

MIF is a progesterone analogue and is known as a potent progesterone antagonist. Although MIF has been known to inhibit prostate cancer cell growth, its molecular mechanisms are not yet clear. In the present study, when the cells were treated for 2-4 days with 5-40 $\mu$M of MIF, the growth and viability of LNCaP cells were significantly decreased in a dose- and time-dependent manner. When the cells, cultivated in a normal 2 mM calcium concentration medium, were treated with 15 $\mu$M MIF for 1 day, the intracellular calcium level increased by 26% compared to the control. Similar results were also found in cells located in the calcium-free reaction buffer, indicating that MIF induced the increase of intracellular Ca$^{2+}$ levels, regardless of the presence of calcium in the surrounding medium. In the cells treated with various concentrations of MIF, the intracellular calcium levels increased in a dose dependent manner. Cells treated with MIF revealed typical early apoptotic signs, i.e., chromosome condensation and nuclei fragmentation. In cells treated with 40 11M MIF, Bcl-2 decreased to 19% of the control. The expression of Bax increased to almost 2 fold of the control. These results demonstrated very clearly that MIF treatment blocks the expression of Bcl-2 but stimulates the expression of Bax. According to the results of the present investigation, the apoptotic mechanism of MIF is triggered by intracellular modulation.

• BMB Reports
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• v.48 no.8
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• pp.461-466
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• 2015

Epigallocatechin gallate (EGCG) and curcumin are well known to naturally-occurring anticancer agents. The aim of this study was to verify the combined beneficial anticancer effects of curcumin and EGCG on PC3 prostate cancer cells, which are resistant to chemotherapy drugs and apoptosis inducers. EGCG showed weaker inhibitory effect on PC3 cell proliferation than two other prostate cancer cell lines, LNCaP and DU145. Co-treatment of curcumin improved antiproliferative effect of EGCG on PC3 cells. The protein expressions of p21 were significantly increased by the co-treatment of EGCG and curcumin, whereas it was not changed by the treatment with each individual compound. Moreover, treatments of EGCG and curcumin arrested both S and G2/M phases of PC3 cells. These results suggest that the enhanced inhibitory effect of EGCG on PC3 cell proliferation by curcumin was mediated by the synergic up-regulation of p21-induced growth arrest and followed cell growth arrest. [BMB Reports 2015; 48(8): 461-466]

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3499-3502
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• 2013

MicroRNAs (miRNAs) are a class of endogenously expressed small, non-coding, single-stranded RNAs that negatively regulate gene expression, mainly by binding to 3'- untranslated regions (3'UTR) of their target messenger RNAs (mRNAs), which cause blocks of translation and/or mRNA cleavage. Recently, miRNAprofiling studies demonstrated the microRNA-497 (miR-497) level to be down-regulated in all prostate carcinomas compared with BPH samples. The purpose of this study was to investigate the potential role of miR-497 in human prostate cancer. Proliferation, cell cycle and apoptosis assays were conducted to explore the potential function of miR-497 in human prostate cancer cells. Results showed that miR-497 suppressed cellular growth and initiated G0/G1 phase arrest of LNCaP and PC-3 cells. We also observed that miR-497 increased the percentage of apoptotic cells by increasing caspase-3/7 activity. Taken together, our results demonstrated that miR-497 can inhibit growth and induce apoptosis by caspase-3 activation in prostate cancer cells, which suggest its use as a potential therapeutic target in the future.

• Korean Journal of Medicinal Crop Science
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• v.20 no.4
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• pp.259-269
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• 2012

This study was performed to determined the antioxidant activities, anticancer and immuno-activities of anthocyanin fraction from Rubus coreanus Miquel fruits (Bokbunja). Anthocyanin fraction extracted from Bokbunja revealed the presence of three anthocyanin components, which were tentatively identified as cyanidin 3-O-sambubioside, cyanidin 3-O-xylosylrutinoside and cyanidin 3-O-rutinoside using RP-HPLC/DAD/MS. The anthocyanin fraction from Bokbunja always showed reducing power and high scavenging activities against DPPH, hydroxy radical (OH) and superoxide anion radical ($O_2{^-}$) similar to general synthetic antioxidant and polyphenol compounds from plant origin. Anthocyanin fraction from Bokbunja showed high inhibition on proliferation of LNCaP and A549 cells and did not inhibit the proliferation of other cancer cells. Immuno-activities of Anthocyanin fraction from Bokbunja were investigated, it showed high promotion of human B and T cells growth about 50% and secretion of IL-6 and TNF-${\alpha}$ by treatment after 6 days. Over all, the result of the study suggest that anthocyanin fraction from Bokbunja displays antioxidant activity comparable to that general synthetic antioxidant, also, anthocyanin fraction from Bokbunja are expected to be good candidate for development into source of anticaner and immuno-activator agent in food industry.

• Molecules and Cells
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• v.38 no.2
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• pp.171-179
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• 2015

Prostatic acid phosphatase (PAP) expression increases proportionally with prostate cancer progression, making it useful in prognosticating intermediate to high-risk prostate cancers. A novel ligand that can specifically bind to PAP would be very helpful for guiding prostate cancer therapy. RNA aptamers bind to target molecules with high specificity and have key advantages such as low immunogenicity and easy synthesis. Here, human PAP-specific aptamers were screened from a 2'-fluoropyrimidine (FY)-modified RNA library by SELEX. The candidate aptamer families were identified within six rounds followed by analysis of their sequences and PAP-specific binding. A gel shift assay was used to identify PAP binding aptamers and the 6N aptamer specifically bound to PAP with a Kd value of 118 nM. RT-PCR and fluorescence labeling analyses revealed that the 6N aptamer bound to PAP-positive mammalian cells, such as PC-3 and LNCaP. IMR-90 negative control cells did not bind the 6N aptamer. Systematic minimization analyses revealed that 50 nucleotide sequences and their two hairpin structures in the 6N 2'-FY RNA aptamer were equally important for PAP binding. Renewed interest in PAP combined with the versatility of RNA aptamers, including conjugation of anti-cancer drugs and nano-imaging probes, could open up a new route for early theragnosis of prostate cancer.

• Biomolecules & Therapeutics
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• v.29 no.6
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• pp.667-677
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• 2021

The elevated expression of the hyaluronan-mediated motility receptor (HMMR) is known to be highly associated with tumor progression in prostate cancer, but the molecular mechanisms underlying the regulation of HMMR expression remain unclear. Here, we report that mammalian target of rapamycin (mTOR) is a key regulator of HMMR expression, for which its kinase activity is required. Pharmacological inhibitors of mTOR, such as rapamycin and Torin2, markedly suppressed the mRNA level as well as the protein level of HMMR in LNCaP and PC-3 cells. Our data demonstrate that such regulation occurs at the transcription level. HMMR promoter reporter assays revealed that the transcription factor SRF is responsible for the mTOR-mediated transcriptional regulation of HMMR gene. Consistently, the suppression of HMMR expression by Torin2 was noticeably reversed by the overexpression of SRF. Moreover, our findings suggest that the SRF binding sites responsible for the transcriptional regulation of HMMR through the mTOR-SRF axis are located in HMMR promoter sequences carrying the first intron, downstream of the translational start site. Furthermore, the upregulation of HMMR by DHT was abolished by stimulation with rapamycin, prior to DHT treatment, suggesting that mTOR activity is required for the induction of HMMR expression by androgen. Collectively, our study provides new mechanistic insights into the role of mTOR/SRF/AR signaling in HMMR regulation in prostate cancer cells.