Novel analogs of 1,25-dihydroxyvitamin D2 combined with a plant polyphenol as highly efficient inducers of differentiation in human acute myeloid leukemia cells

Nachliely, Matan; Sharony, Ehud; Kutner, Andrzej; Danilenko, Michael

doi:10.1016/j.jsbmb.2015.09.014

Cited by 26 publications

(29 citation statements)

References 30 publications

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“…One such agent which is used is 1α25-dihydroxyviatmin D (1,25D). Many studies have found that low doses of CA (5–10 µM) are able to potentiate the pro-differentiation effects of 1,25D and help sensitize leukemia cells including human HL-60, U937, MOLM-13 and mouse WEHI-3B cells [40,41,71,72,73,74,75,76,77,78] to its anticancer effects (Table 11). Furthermore, CA inhibited cell viability and induced apoptosis and cell cycle arrest in these cells using a multitude of different strategies.…”

Section: Anticancer Effects Of Carnosic Acid (Ca): In Vitro Studiesmentioning

confidence: 99%

Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols

2016

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Cancer cells display enhanced growth rates and a resistance to apoptosis. The ability of cancer cells to evade homeostasis and proliferate uncontrollably while avoiding programmed cell death/apoptosis is acquired through mutations to key signaling molecules, which regulate pathways involved in cell proliferation and survival. Compounds of plant origin, including food components, have attracted scientific attention for use as agents for cancer prevention and treatment. The exploration into natural products offers great opportunity to evaluate new anticancer agents as well as understand novel and potentially relevant mechanisms of action. Rosemary extract has been reported to have antioxidant, anti-inflammatory, antidiabetic and anticancer properties. Rosemary extract contains many polyphenols with carnosic acid and rosmarinic acid found in highest concentrations. The present review summarizes the existing in vitro and in vivo studies focusing on the anticancer effects of rosemary extract and the rosemary extract polyphenols carnosic acid and rosmarinic acid, and their effects on key signaling molecules.

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Section: Anticancer Effects Of Carnosic Acid (Ca): In Vitro Studiesmentioning

confidence: 99%

Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols

2016

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“…In our continuous search for more active vitamin D analogs for use as potential therapeutics [ 44 ], we have investigated the analogs of 1,25-dihydroxyvitamin D 2 (1,25(OH) 2 D 2 ) [ 45 ]. Following the discovery [ 46 ] of an ample free space around the terminal part of the side-chain we designed [ 47 ], synthesized [ 48 ] and investigated the biological activity of side-chain homologated analogs [ 49 ]. A favorable activity profile was observed for analogs containing a side chain with an ATRA-like all- trans geometry [ 50 ].…”

Section: Introductionmentioning

confidence: 99%

Antiproliferative Activity of Double Point Modified Analogs of 1,25-Dihydroxyvitamin D2 Against Human Malignant Melanoma Cell Lines

Piotrowska

Wierzbicka

Nadkarni

et al. 2016

IJMS

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Vitamin D is a lipid soluble steroid hormone with pleiotropic biological properties, including regulation of cell proliferation, differentiation and apoptosis. As to these desirable anticancer actions, 1,25-dihydroxyvitamins D and analogs have been reported to inhibit the proliferation and to induce differentiation of a wide variety of cancer cell types, including human malignant melanoma. However, there is a need for novel and more efficacious vitamin D analogs, and how best to design such is still an open issue. A series of double point modified (DPM) analogs of 1,25-dihydroxyvitamin D2 (1,25(OH)2D2) induced differentiation of the vitamin D receptor (VDR) positive A375 and VDR negative SK-MEL 188b human malignant melanoma cell lines. Surprisingly, the dose of 1,25(OH)2D2 required to inhibit the proliferation of the A375 melanoma cell line by was several fold lower than that required in the case of 1,25(OH)2D3. To evaluate the impact of the modification in the side chain (additional 22-hydroxyl) and in the A-ring (5,6-trans modification), the regular side-chain of vitamin D2 or D3 was retained in the structure of our analogs. As expected, 5,6-trans modification was advantageous to enhancing the anti-proliferative activity of analogs, but not as a single point modification (SPM). Very unexpectedly, the additional 22-hydroxyl in the side-chain reduced significantly the anti-proliferative activity of both the natural and 5,6-trans series analogs. Finally, an induction of pigmentation in melanoma SK-MEL 188b cells was observed to sensitized cells to the effect of vitamin D analogs.

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“…Diluted solution of 5-FU was added to cell culture at a final concentration of 6 μg/mL (46 μM). 1,25D3, 1,25D2, PRI-2191 [(24 R )-1,24-dihydroxyvitamin D 3 , tacalcitol], PRI-1906, PRI-1907, PRI-1916, and PRI-1917 were synthesized at the Pharmaceutical Research Institute, Warsaw, Poland [ 62 , 63 , 64 , 65 ]. Samples of analogues were aliquoted to amber ampoules and dried down in a stream of argon.…”

Section: Methodsmentioning

confidence: 99%

The Effect of Analogues of 1α,25-Dihydroxyvitamin D2 on the Regrowth and Gene Expression of Human Colon Cancer Cells Refractory to 5-Fluorouracil

Neska

Swoboda

Przybyszewska

et al. 2016

IJMS

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This study aimed to evaluate the capacity of hypocalcemic analogues of 1α,25-dihydroxyvitamin D2 (1,25D2) and 1α,25-dihydroxyvitamin D3 (1,25D3) to inhibit regrowth and regulate the stemness-related gene expression in colon cancer cells undergoing renewal after exposure to 5-fluorouracil (5-FU). All of the tested analogues of 1,25D2 equally potently decreased the clonogenicity and the proliferative activity of HT-29 cells which survived the exposure to 5-FU, but differently regulated gene expression of these cells during their renewal. 1,25D2 and analogues (PRI-1907 and PRI-1917), as well as 1,25D3 and analogue PRI-2191, decreased the relative expression level of several stemness-related genes, such as NANOG, OCT3/4, PROM1, SOX2, ALDHA1, CXCR4, in HT-29/5-FU cells during their renewal, in comparison to untreated HT-29/5-FU cells. The other 1,25D2 analogues (PRI-1906 and PRI-1916) were not capable of downregulating the expression of these stemness-related genes as the analogues PRI-1907 and PRI-1917 did. All of the tested vitamin D analogues upregulated CDH1, the gene encoding E-cadherin associated with epithelial phenotype. Out of the series of analogues studied, side-chain branched analogues of 1,25D2 (PRI-1907, PRI-1917) and the analogue of 1,25D3 (PRI-2191) might be used to target cancer cells with stem-like phenotypes that survive conventional chemotherapy.

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Novel analogs of 1,25-dihydroxyvitamin D2 combined with a plant polyphenol as highly efficient inducers of differentiation in human acute myeloid leukemia cells

Cited by 26 publications

References 30 publications

Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols

Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols

Antiproliferative Activity of Double Point Modified Analogs of 1,25-Dihydroxyvitamin D2 Against Human Malignant Melanoma Cell Lines

The Effect of Analogues of 1α,25-Dihydroxyvitamin D2 on the Regrowth and Gene Expression of Human Colon Cancer Cells Refractory to 5-Fluorouracil

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