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A Conserved Mechanism for Binding of p53 DNA-Binding Domain and Anti-Apoptotic Bcl-2 Family Proteins

  • Lee, Dong-Hwa;Ha, Ji-Hyang;Kim, Yul;Jang, Mi;Park, Sung Jean;Yoon, Ho Sup;Kim, Eun-Hee;Bae, Kwang-Hee;Park, Byoung Chul;Park, Sung Goo;Yi, Gwan-Su;Chi, Seung-Wook
    • Molecules and Cells
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    • v.37 no.3
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    • pp.264-269
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    • 2014
  • The molecular interaction between tumor suppressor p53 and the anti-apoptotic Bcl-2 family proteins plays an essential role in the transcription-independent apoptotic pathway of p53. In this study, we investigated the binding of p53 DNA-binding domain (p53DBD) with the anti-apoptotic Bcl-2 family proteins, Bcl-w, Mcl-1, and Bcl-2, using GST pull-down assay and NMR spectroscopy. The GST pull-down assays and NMR experiments demonstrated the direct binding of the p53DBD with Bcl-w, Mcl-1, and Bcl-2. Further, NMR chemical shift perturbation data showed that Bcl-w and Mcl-1 bind to the positively charged DNA-binding surface of p53DBD. Noticeably, the refined structural models of the complexes between p53DBD and Bcl-w, Mcl-1, and Bcl-2 showed that the binding mode of p53DBD is highly conserved among the anti-apoptotic Bcl-2 family proteins. Furthermore, the chemical shift perturbations on Bcl-w, Mcl-1, and Bcl-2 induced by p53DBD binding occurred not only at the p53DBD-binding acidic region but also at the BH3 peptide-binding pocket, which suggests an allosteric conformational change similar to that observed in Bcl-$X_L$. Taken altogether, our results revealed a structural basis for a conserved binding mechanism between p53DBD and the anti-apoptotic Bcl-2 family proteins, which shed light on to the molecular understanding of the transcription-independent apoptosis pathway of p53.

Tandem Mass Spectrometric Analysis for Disorders in Amino, Organic and Fatty Acid Metabolism : 2 Years of SCL Experience in Korea

  • Yoon, Hye-Ran;Lee, Kyung Ryul
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.3 no.1
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    • pp.86-93
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    • 2003
  • Background : The SCL began screening of newborns and high risk group blood spots with tandem mass spectrometry (MS/MS) in April 2001. Our goal was to determine approximate prevalence of metabolic disorders, optimization of decision criteria for estimation of preventive effect with early diagnosis. This report describes the ongoing effort to identify more than 30 metabolic disorders by MS/MS in South Korea. Methods : Blood spot was collected from day 2 to 30 (mostly from day 2 to 10) after birth for newborn. Blood spot of high risk group was from the pediatric patients in NICU, developmental delay, mental retardation, strong family history of metabolic disorders. One punch (3.2 mm ID) of dried blood spots was extracted with $150{\mu}L$ of methanol containing isotopically labelled amino acids (AA) and acylcarnitines (AC) internal standards. Butanolic HCl was added and incubated at $65^{\circ}C$ for 15 min. The butylated extract was introduced into the inlet of MS/MS. Neutral loss of m/z 102 and parent ion mode of m/z 85 were set for the analyses of AA and AC, respectively. Diagnosis was confirmed by repeating acylcarnitine profile, urine organic acid and plasma amino acid analysis, direct enzyme assay, or molecular testing. Results : Approximately 31,000 neonates and children were screened and the estimated prevalence (newborn/high risk group), sensitivity, specificity and recall rate amounted to 1:2384/1:2066, 96.55%, 99.98%, and 0.73%, respectively. Confirmed 28 (0.09%) multiple metabolic disorders (newborn/high risk) were as follows; 13 amino acid disorders [classical PKU (3/4), BH4 deficient-hyperphenylalaninemia (0/1), Citrullinemia (1/0), Homocystinuria (0/2), Hypermethioninemia (0/1), Tyrosinemia (1/0)], 8 organic acidurias [Propionic aciduria (2/1), Methylmalonic aciduria (0/1), Isovaleric aciduria (1/1), 3-methylcrotonylglycineuria (1/0), Glutaric aciduria type1 (1/0)], 7 fatty acid oxidation disorders [LCHAD def. (2/2), Mitochondrial TFP def. (0/1), VLCAD def. (1/0), LC3KT def. (0/1). Conclnsion : The relatively normal development of 10 patients with metabolic disorders among newborns (except for the expired) demonstrates the usefulness of newborn screening by MS/MS for early diagnosis and medical intervention. However, close coordination between the MS/MS screening laboratory and the metabolic clinic/biochmical geneticists is needed to determine proper decision of screening parameters, confirmation diagnosis, follow-up scheme and additional tests.

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Efficient Synthesis of hypho-2,5-$S_2B_7H_{11}$ and Preparation of New nido-, arachno-, and hypho-Metalladithiaborane Clusters Derived from Its Anion hypho-$S_2B_7H_{10}{^-}$

  • 강창환;김성준;고재정;강상욱
    • Bulletin of the Korean Chemical Society
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    • v.16 no.11
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    • pp.1067-1074
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    • 1995
  • Reaction of arachno-S2B7H8- with either THF or 1,2-dimethoxyethane upon refluxing condition results in the formation of the previously known compound hypho-S2B7H10-. Protonation of hypho-S2B7H10- with HCl/Et2O generates hypho-2,5-S2B7H11 in good yield. This hypho-S2B7H10- anion has been employed to generate a series of new nido-, arachno-, and hypho-metalladithiaborane clusters. Reaction of the anion with Cp(CO)2FeCl results in direct metal insertion and the formation of a complex containing the general formula (η5-C5H5)FeS2B7H8. Spectroscopic studies of nido-6-CpFe-7,9-S2B7H8 Ⅰ demonstrated that compound Ⅰ was shown to have an nido-type cage geometry derived from an octadecahedron missing one vertex, with the iron atom occupying the three-coordinate 6-position in the cage and the two sulfurs occupying positions on the open face of the cage. Reaction of hypho-S2B7H10- with CoCl2/Li+[C5H5]- gave the previously known complex arachno-7-CpCo-6,8-S2B6H8 Ⅱ. Also, the reaction of the anion with [Cp*RhCl2]2 gave the complex arachno-7-Cp*Rh-6,8-S2B6H8 Ⅲ, the structure of which was shown to be that of complex Ⅱ. The similarity of the NMR spectra of Ⅱ and Ⅲ suggest that Ⅲ adopts cage structure similar to that previously confirmed for Ⅱ. A series of 9-vertex hypho clusters in which the sulfur atoms are bridged by different species isoelectronic with a BH3 unit, such as HMn(CO)4 or SiR2 have been prepared. Compounds Ⅳ,Ⅴ and Ⅵ are each 2n+4 skeletal electron systems and would be expected according to skeletal electron counting theory to adopt hypho-type polyhedral structures derived from an icosahedron missing three vertices. The complex hypho-1-(CO)4Mn-2,5-S2B6H9 Ⅳ was obtained by the reaction of the anion with (CO)5MnBr and has been shown from spectroscopic data to consist of a (CO)4Mn fragment bound to the two sulfur atoms S2 and S5 of hypho-S2B7H10-. Also, similar hypho-type complexes hypho-1-R2Si-2,5-S2B6H8 (R=CH3 Ⅴ, R=C6H5 Ⅵ) have been prepared from the reaction of hypho-S2B7H10- with R2SiHCl.

Synthesis of LiDAR-reflective Hollow-structured Black Materials and Recycling of Their Etched Waste for Semiconductor Epoxy Molding Compound (라이다 반사형 중공구조 검은색 물질의 개발 및 코어 에칭 폐액 재활용을 통한 반도체용 에폭시 몰딩 컴파운드 응용)

  • Ha-Yeong Kim;Min Jeong Kim;Jiwon Kim;Suk Jekal;Seon-Young Park;Jong Moon Jung;Chang-Min Yoon
    • Journal of the Korea Organic Resources Recycling Association
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    • v.31 no.1
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    • pp.5-14
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    • 2023
  • In this study, LiDAR-reflective black hollow-structured silica/titania(B-HST) materials are successfully synthesized by employing the NaBH4 reduction and etching method on silica/titania core/shell(STCS) materials, which also effectively enhance near-infrared(NIR) reflectance. Moreover, core-etched supernatant solutions are collected and recycled for the synthesis of extracted silica(e-SiO2) process, which successfully applies as filler materials for semiconductor epoxy molding compound(EMC). In detail, B-HST materials, fabricated by the sequential experimental steps of sol-gel, reduction, and sonication-mediated etching method, manifest blackness(L*) of 13.2 similar to black paint and excellent NIR reflectance(31.1%). Consequently, B-HST materials are successfully prepared as LiDAR-reflective black materials. Additionally, core-etched supernatant solution with silanol precursors are employed for synthesis of homogeneous silica filler materials via sol-gel method. As-synthesized silica fillers are incorporated with epoxy resin and carbon black for the preparation of semiconductor EMC. Experimentally synthesized EMC exhibits comparable mechanical-chemical properties to commercial EMC. Conclusively, this study successfully proposes designing procedure and practical experimental method for simultaneously synthesizing the NIR-reflective black materials for self-driving vehicles and EMC materials for semiconductors, which are materials suitable for the industrial 4.0 era, and presented their applicability in future industries.

Estimation of Heritability and Genetic Parameter for Growth and Body Traits of Pig (종돈의 성장 및 체형 형질에 대한 유전력 및 유전모수 추정에 관한 연구)

  • Kang, Hyun-Sung;Nam, Ki-Chang;Kim, Kyung-Tai;Na, Chong-Sam;Seo, Kang-Seok
    • Journal of Animal Science and Technology
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    • v.54 no.2
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    • pp.83-87
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    • 2012
  • The purpose of this study was to estimate genetic parameters for productive traits in swine. Productive traits were considered on average daily gain (ADG), body height (BH) and body length (BL). Genetic analysis was consisted of 18,668 heads for productive traits which were based on on-farm performance tested from May, 2007 to Apr, 2011. For estimating genetic parameters on productive traits, single best model was fitted after finding source of variance on fixed and random effects and estimated with a multiple trait animal model by using DF-REML (Derivative-Free Restricted Maximum Likelihood). The estimated heritabilities of Duroc, Berkshire, Landrace and Yorkshire 0.22-0.58 for the average daily gain, 0.34-0.41 for the body height and 0.4-0.52 for the body length, respectively. Phenotypic correlations of average daily gain with body height and body length for the four breeds were 0.42-0.48, 0.53-0.58, 0.34-0.46 and 0.47-0.56, respectively. Phenotypic correlations of body height with body length were 0.41, 0.57, 0.52, 0.59, respectively. The estimated genetic correlation coefficients of average daily gain with body height and body length estimated for the four breeds were 0.34-0.47, 0.70-0.75, 0.17-0.38 and 0.50-0.53, respectively. The estimated genetic correlation coefficients of body height with body length were 0.57, 0.69, 0.61 and 0.71, respectively.

Growth, Body shape and Carcass cutting yield traits of Duroc and Crossbred(Duroc×Pietrain×Pietrain)pigs (두록과 교잡돈(두록×피어트레인×피어트레인)의 성장, 체형형질 및 도체 부분육 생산량 비교)

  • Kim, Young Sin;Kim, JeongA;Jeong, Yong Dae;Choi, Yo Han;Cho, Eun Seok;Chung, Hak Jae;Sa, Soo Jin;Beak, Sun Young;Hong, Joon Ki
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.21 no.7
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    • pp.255-261
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    • 2020
  • This study was undertaken to evaluate the growth, body shape and carcass cutting yield traits of Duroc (D) and crossbred (Duroc×Pietrain×Pietrain; DPP) pigs. A total of 147 D and 101 DPP pigs were used for analyzing the growth trait, whereas 16 D and 16 DPP pigs were evaluated for carcass yields. Backfat thickness (BF) and average daily feed intake (ADFI) were significantly higher in D (14.07±0.24 mm, 2,101 g) than in DPP (12.69±3.25 mm, 1,909 g) (p <0.001). Moreover, D exhibited significantly higher body shape traits including body height (BH), chest depth (CD) and chest width (CW), as compared to DPP pigs (p <0.001). No differences were observed for body length (BL) between the two strains. Analysis of the carcass cutting yield traits determined for D and DPP were in the order: ham (HM; 31.17% and 33.43%), belly (BY; 23.40% and 19.55%), and picnic shoulder (PS; 16.54% and 16.87%), respectively. Then, HM showed a difference of 2.26% P with D(31.17%) and DPP(33.43%), while BY showed a difference of 3.85% P with D(23.40%) and DPP(19.55%). Taken together, our results indicate that DPP has a better feed efficiency than D, and therefore has the potential to increase the production of low-fat pork, targeting consumers having a high preference who have opted for a healthy lifestyle. These results can be used as basic data for developing an ideal pig breed.

Comparison of Carotenoid Pigments on Manchurian Trout, Brachymystax lenok and Masu Salmon, Oncorhynchus macrostomus in the Family Salmonidae (연어과에 속하는 열목어와 산천어의 Carotenoid 색소성분의 비교)

  • BAEK Sung-Han;HA Bong-Seuk
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.31 no.2
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    • pp.278-287
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    • 1998
  • Carotenoids in integument of wild manchurian trout, Brachymystax lenok, and wild and cultured masu salmon Oncohynchus macrostomus, which are all the Korean native cold fresh water fish, were investigated by thin layer chromatography, column chromatography and HPLC. The total carotenoid contents of the wild manchurian trout were $3.72\;mg\%$ which is relatively higher compare to other species of salmonidae. The carotenoids were composed of $36.9\%$ zeaxanthin and $14.7\%$ $\beta-carotene$ as the major compounds, $7.8\%$ triol $7.3\%$ isocryptoxanthin, $5.7\%$ 4-hydroxy echinenone, $4.7\%$ lutein, $4.5\%$ salmoxanthin and $2.2\%$ astaxanthin as minor compounds, and other carotenoids such as canthaxanthin, tunaxanthin A, tunaxanthin B, tunaxanthin C, $\beta-cryptoxanthin$ and $\alpha-cryptoxanthin$ as minute carotenoids. Wild masu salmon contained more total carotenoids than cultured one and the contents were $0.82\;mg\%$ and $0.66\;mg\%$, respectively. The composition of the carotenoids from wild masu salmon were $20.7\%$ xeaxanthin, $17.0\%$ isocryptoxanthin and $15.8\%\;\beta-carotene$ as major compounds, and $6.2\%$ triol, $6.1\%$ 4-hydroxy echinenone, $6.1\%$ salmoxanthin, $5.9\%$ canthaxanthin, $5.8\%$ lutein, $4.9\%$ $\alpha-cryptoxanthin$ and $1.0\%$ astaxanthin as minor compounds. The composition of the carotenoids from cultured masu salmon were $19.7\%$ isocryptoxanthin, $18.0\%$ $\beta-carotene$ and $10.3\%$ zeaxanthin as the major compounds, and $8.9\%\;\beta-cryptoxanthin$, $8.5\%\;\alpha-cryptoxanthin$, $8.0\%$ lutein, $7.6\%$ canthaxanthin, $5.1\%$ triol and $2.0\%$ astaxanthin as minor carotenoids. Based on these data, wild masu salmon contained more zeaxanthin, salmoxanthin and 4-hydroxy echinenone while cultured masu salmon contained more $\alpha-cryptoxanthin$, indicating that carotenoid pigment of masu salmon depends on their living conditions. Unlike wild masu salmon, 4-hydroxy echinenone and salmoxanthin which are the characteristic carotenoids of salmons, were not found in the integument of cultured masu salmon. Unlike manchurian trout, both wild and cultured masu salmon did not contain tunaxanthin A, tunaxanthin B and tunaxanthin C.

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Inhibitory Action of Natural Food Components on the Formation of Carcinogenic Nitrosamine (천연식품성분에 의한 발암성 니트로사민의 생성억제작용)

  • AHN Bang-Weon;LEE Dong-Ho;YEO Saeng-Gyu;KANG Jin-Hoon;DO Jeong-Ryong;KIM Seon-Bong;PARK Yeung-Ho
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.26 no.4
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    • pp.289-295
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    • 1993
  • The present paper was investigated in the inhibitory action of vegetable and seaweed water-soluble extracts on the formation of carcinogenic N-nitrosodimethylamine(NDMA). The vegetable and seaweed extracts obtained from garlic(Allium sativum), onion(Allium cepa), green onion(Allium fistuiosum), chinese pepper(Fagara mandshurica), green pepper(Capsicum annuum), red pepper(Capsicum annuum), ginger(Zingiber officinale), carrot(Daucus carota), laver(Porphyra tenera), sea lettuce(Entero compresa), sea mustard(Undaria pinnatifida) and sea staghorn(Codium fragile) were incubated with sodium nitrite-dimethylamine mixtures at $37^{\circ}C$ under different pH conditions The formation of NDMA was reduced to $10{\sim}40\%\;and\;25{\sim}50\%$ by the addition of vegetable and seaweed extracts 30mg at pH 1.2, respectively. The inhibition degree by the extracts at pH 1.2 was similiar to that at pH 4.2 and to that by ascorbic acid at pH 1.2. The inhibitory action of the extracts against NDMA formation was not decreased by heat treatment at $80^{\circ}C$ for 10min, but decreased by the treatment of sodium borohydride. It is assumed that reducing powers of the extracts participated in their inhibitory actions.

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Comparison of Growth, Yield and Quality by Green Crop Treatments in Rice (Oryza sativa L.) Organic Cultivation (벼 유기재배 시 녹비작물 처리에 의한 작물의 생육, 수량 및 품질 비교)

  • Cha, Kwang-Hong;Oh, Hwan-Jung;Park, Heung-Gyu;An, Kyu-Nam;Park, Ro-Dong;Jung, Woo-Jin
    • Korean Journal of Organic Agriculture
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    • v.19 no.1
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    • pp.55-64
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    • 2011
  • To investigate a comparison of rice yield and quality by a utilization of green crops using barley and hairyvetch, this study was carried out in rice (Oryza sativa L.) organic cultivation field. Convention barley harvest (CBH), Green barley crop (GBC), Green barley+Green Hairyvetch crop (GB+HVC), and Non-Green crop (NGC) were treated in rice cultivation field. The results obtained as following: 1) Culm length and pancile length in Convention barley harvest (CBH) cultivation were longer than organic cultivation but were not significant difference in all treatments. Yields of milled rice in Green barley crop (GBC) and Green barley+Green Hairyvetch crop (GB+HVC) were by 90.3% and 95.9%, respectively. 2) Protein contents in Green barley crop (GBC) and Green barley+Green Hairyvetch crop (GB+HVC) were by 5.7% lower than 6.6% in Convention barley harvest (CBH) cultivation. Amylose contents in all treatment were similar as range 18.8% to 19.1%. Whiteness contents in Green barley crop (GBC) and Green barley+Green Hairyvetch crop (GB+HVC) were slightly higher by 38.9% and 39.1%, respectively, than 37.7% in Convention barley harvest (CBH) cultivation. 3) Palatability values in Barley harvest (BH) and Non-Green crop (NGC) were slightly higher by 82.0 and 83.8, respectively, than 77.6 in Convention barley harvest (CBH) cultivation. 4) Head rice in Non-Green crop (NGC) was 95.5%, while that of Convention barley harvest (CBH), Green barley crop (GBC), and Green barley+Green Hairy-vetch crop (GB+HVC) were slightly low as range 93.8% to 94.2%. White core and belly rice in Convention barley harvest (CBH) cultivation was the highest level by 1.7%. 5) Leaf blast, neck blast, sheath blight, rice stem maggot, rice leaf roller, rice leaf-tier, and green rice leafhopper were occurred lightly in rice field.

Inhibitory Effect of the Hexane Extract of Saussurea lappa on the Growth of LNCaP Human Prostate Cancer Cells (목향 헥산추출물의 LNCaP 전립선암세포 증식 억제 효과)

  • Park, So-Young;Kim, Eun-Ji;Lim, Do-Young;Kim, Jong-Sang;Lim, Soon-Sung;Shin, Hyun-Kyung;Yoon Park, Jung-Han
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.1
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    • pp.8-15
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    • 2008
  • Saussurea lappa (SL) has been used to reduce abdominal pain and tenesmus in traditional oriental medicine. SL and major compounds of SL, sesquiterpene lactones, have been suggested to possess various biological effects, including anti-tumor, anti-ulcer, anti-inflammatory, anti-viral and cardiotonic activities. Recently, it has been reported that ethanol extracts from roots of SL have antiproliferative effects on gastric cancer cells. To explore the possibility that SL has chemopreventive effects on prostate cancer, we examined whether the hexane extract of SL (HESL) inhibits the growth of LNCaP human prostate cancer cells. Cells were incubated with various concentrations ($0{\sim}4$ mg/L) of HESL in DMEM/F12 containing 5% charcoal stripped fetal bovine serum. HESL substantially decreased viable cell numbers and induced apoptosis of LNCaP cells in dose-dependent manners. HESL increased the levels of cleaved caspase-8, -9, -7 and -3, and poly (ADP-ribose) polymerase. HESL increased the levels of the pro-apoptotic Bak and truncated-Bid proteins whereas it had no effect on the anti-apoptotic Bcl-2, Bcl-xL, or Mcl-1. The present results indicate that HESL inhibits the growth of human prostate cancer cells by inducing apoptosis, which involves the activation of the caspase cascades.