Epidemiological evidence has correlated consumption of sorghum with reduced incidences of gastrointestinal (GI) tract cancer, especially esophageal cancer. There is little evidence on how phenols of sorghum may affect chemoprevention. Seventeen sorghum varieties were screened for phenolic profiles and antioxidant capacity. The ability of crude sorghum extracts to induce NAD(P)H:quinone oxidoreductase (QR, a phase II protective enzyme), and inhibit proliferation of colon (HT-29) and esophageal (OE33) carcinoma cells using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) and PicoGreen assays, were determined in vitro. 3- Deoxyanthocyanidins, apigeninidin, luteolinidin and their methoxylated derivatives were also investigated for antioxidant capacity, QR inducing and antiproliferative potential. Tannin sorghum generally showed higher antioxidant capacity than non-tannin sorghum varieties. Sorghum varieties containing extractable condensed tannins did not show any significant QR inducing potential; on the other hand, non-tannin sorghums increased QR activity by 1.5-2.7 times; black sorghum (Tx430) was most potent (doubled QR activity at 25 mg/mL, 2.7-fold increase at 100 mg/mL). All sorghum extracts showed relatively strong antiproliferation activity with IC50s (the concentration needed to inhibit cancer cell growth by 50%) of 49.7-883 mg/mL. Tannin-containing sorghums had stronger cancer cell proliferation inhibitory potential (IC50s 49.7-131 mg/mL) than non-tannin sorghums (IC50s 141-883 mg/mL). Total phenol content and antioxidant capacity of crude sorghum extracts positively correlated with their antiproliferative potential (r2 0.71-0.97). Among tested 3-deoxyanthocyanidins, methoxylation on A-ring improved QR inducing potency. 5,7-Dimethoxyluteolinidin had the greatest QR inducing potency (4.3- fold at 100 mM). Methoxylation also improved their antiproliferation potential; the IC50s trend was di-methoxylated (8.3-105 mM) > mono-methoxylated (40.1-192 mM) > apigeninidin and luteolinidin (81.5-284 mM). This study provides information for how phenolic compositions of sorghum and 3-deoxyanthocyanidin structure affect their capacity to induce QR activity and inhibit GI tract cancer cell proliferation. The information is useful to promote the utilization of sorghum in functional foods, beverages, dietary supplements, and other health-related industries. Further study will focus on, fractioned and isolated sorghum phenols, the effect of food processing on their chemopreventive potential, as well as cellular mechanisms involved.

1,25-(OH)2 vitamin D3 inhibits cell proliferation of a variety of cancers including prostate. In the human prostate cancer cell line LNCaP, 1,25-(OH)2 vitamin D3-mediated growth inhibition is attributed to cell cycle G1 accumulation which correlates with a robust decrease of cyclin-dependent kinase 2 (CDK2) activity and pronounced relocalization of CDK2 into the cytoplasm. Nuclear targeting CDK2 blocks the 1,25-(OH)2 vitamin D3-mediated growth inhibition and cell cycle G1 accumulation. Further, the nuclear targeted CDK2 blocks 1,25-(OH)2 vitamin D3-mediated inhibition of CDK2 activity and nuclear exclusion in LNCaP cells. Therefore, CDK2 cytoplasmic relocalization is the key mechanism for 1,25-(OH)2 vitamin D3 effects. Since cyclin E is important for CDK2 nuclear localization and activation, 1,25-(OH)2 vitamin D3 may exert its effects through regulation of cyclin E. Cyclin E but not a cyclin E mutant deficient in CDK2 binding reverses 1,25-(OH)2 vitamin D3-mediated antiproliferation which suggests the involvement of cyclin E as a mechanism. However, the studies showed no effects of 1,25-(OH)2 vitamin D3 on cyclin E levels, intracellular localization or binding to CDK2. In order to develop a model for studying 1,25-(OH)2 vitamin D3-mediated antiproliferative effects, LNCaP vitD.R cell line, a vitamin D resistant LNCaP derivative, was generated by continuously culturing of LNCaP cells in medium supplemented with 10 nM 1,25-(OH)2 vitamin D3 for over 9 months. The initial characterization of this cell line showed complete resistance to 1,25-(OH)2 vitamin D3-mediated effects. Analysis of vitamin D regulation of VDR target gene expression revealed that vitamin D resistance in LNCaP vitD.R cells was not due to deregulation of VDR signaling. HDAC inhibitor Trichostatin A (TSA) did not confer sensitivity of LNCaP vitD.R cells to vitamin D treatment suggested the resistance to 1,25(OH)2 vitamin D3 effect of LNCaP vitD.R cells is not due to histone deacetylase remodeling of the chromatin structure which leads to inhibition of gene transcription. While the partial sensitization of LNCaP vitD.R cells to 1,25(OH)2 vitamin D3 effect by demethylation reagent 5-Aza-2¡¯-deoxycytidine treatment suggested a set of genes involved in 1,25(OH)2 vitamin D3-mediated antiproliferative effects is silenced via hypermethylation in LNCaP vitD.R cells. These results suggested LNCaP vitD. R cell line is a useful tool and further studies to elucidate the genes involved in this effect will help uncover the mechanisms of 1,25(OH)2 vitamin D3-mediated antiproliferative effects.

<p>Cancer or malignant tumors has a high death frequency in many countries. Nowadays many research facilities are dedicated to find new substances and techniques which would lead to better cancer therapies. Seven years ago a research team from Finland made a remarkable connection between vitamin D deficiencies and an increased chance of getting prostate cancer. The research investigating this statement has lead to findings of a new non-classical effect of the calcium controlling vitamin, 1,25(OH)2D3. This effect involves anti-proliferatory effects and more importantly apoptotic effects resulting in the hope of finding a new drug that can cure prostate cancer with the smallest amount of harm to the body.</p><p>In an attempt to find out if the signalling pathway of this apoptotic effect is fast or slow, an experiment designed to detect when the apoptotic protein caspase-3 is induced has been performed. Cells from the cell line LNCaP has been cultured and incubated with 1,25(OH)2D3 and after 0min - 48h an assay was performed to detect the relative amounts of caspase-3 present in every sample. The optimal time period (48h) was then subjected to three different concentrations of 1,25(OH)2D3 and read in the same way as the previous samples. The results showed an increase in caspase-3 expression as early as 2 min, but disappear to be seen again at 24h and are more profound in 48h samples. The caspase-3 expression was also seen to form a possible exponential curve in dose-response.</p>

Cancer or malignant tumors has a high death frequency in many countries. Nowadays many research facilities are dedicated to find new substances and techniques which would lead to better cancer therapies. Seven years ago a research team from Finland made a remarkable connection between vitamin D deficiencies and an increased chance of getting prostate cancer. The research investigating this statement has lead to findings of a new non-classical effect of the calcium controlling vitamin, 1,25(OH)2D3. This effect involves anti-proliferatory effects and more importantly apoptotic effects resulting in the hope of finding a new drug that can cure prostate cancer with the smallest amount of harm to the body. In an attempt to find out if the signalling pathway of this apoptotic effect is fast or slow, an experiment designed to detect when the apoptotic protein caspase-3 is induced has been performed. Cells from the cell line LNCaP has been cultured and incubated with 1,25(OH)2D3 and after 0min - 48h an assay was performed to detect the relative amounts of caspase-3 present in every sample. The optimal time period (48h) was then subjected to three different concentrations of 1,25(OH)2D3 and read in the same way as the previous samples. The results showed an increase in caspase-3 expression as early as 2 min, but disappear to be seen again at 24h and are more profound in 48h samples. The caspase-3 expression was also seen to form a possible exponential curve in dose-response.