Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

4-(Hydroxyphenyl)retinamide (4-HPR) is a synthetic retinoid with a strong apoptotic effect towards different cancer cell lines in vitro, and it is currently tested in clinical trials. Increases of reactive oxygen species (ROS) and modulation of endogenous sphingolipid levels are well-described events observed upon 4-HPR treatment, but there is still a lack of understanding of their relationship and their contribution to cell death. LC-MS analysis of sphingolipids revealed that in human leukemia CCRF-CEM and Jurkat cells, 4-HPR induced dihydroceramide but not ceramide accumulation even at sublethal concentrations. Myriocin prevented the 4-HPR-induced dihydroceramide accumulation, but it did not prevent the loss of viability and increase of intracellular ROS production. On the other hand, ascorbic acid, Trolox, and vitamin E reversed 4-HPR effects on cell death but not dihydroceramide accumulation. NDGA, described as a lipoxygenase inhibitor, exerted a significantly higher antioxidant activity than vitamin E and abrogated 4-HPR-mediated ROS. It did not however rescue cellular viability. Taken together, this study demonstrates that early changes observed upon 4-HPR treatment, i.e., sphingolipid modulation and ROS production, are mechanistically independent events. Furthermore, the results indicate that 4-HPR-driven cell death may occur even in the absence of dihydroceramide or ROS accumulation. These observations should be taken into account for an improved design of drug combinations.
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PMID:Dihydroceramide accumulation and reactive oxygen species are distinct and nonessential events in 4-HPR-mediated leukemia cell death. 2242 32

In this study, the antioxidative and anti-inflammatory potential of crude extracts (CE), anthocyanin-rich fractions (ARF), and phenolic fractions (PF) from raspberry (R) and raspberry juice (J) were evaluated. The antioxidant properties were evaluated with three complementary assays: DPPH radical scavenging activity, chelating Fe(II) power, and ferric reducing power. The highest antioxidant activity was determined for the crude extract from raspberry pulp (RCE) in the case of all methods used. The anti-inflammatory activity was demonstrated by inhibitory effect on lipoxygenase (LOX) and cyclooxygenase-2 (COX-2) activity in vitro. The highest efficiency in inhibiting the activity of both enzymes was exhibited by RCE, 0.79 and 0.59 mg FW/mL, respectively. In turn, JARF had the lowest ability to inhibit LOX (EC50 = 4.5 mg FW/mL) and JPF caused the lowest COX-2 inhibition (1.75 mg FW/mL). Additionally, we have performed a pilot study of in vitro cytotoxic activity using two human leukemia cell lines: J45 and HL60. All examined extracts inhibited the viability of J45 cells more effectively than HL60. The highest cytotoxic effect was observed in the J45.01 cell line after exposure to RCE (EC50 = 0.0375 mg FW/mL).
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PMID:Antioxidant, Anti-Inflammatory, and Postulated Cytotoxic Activity of Phenolic and Anthocyanin-Rich Fractions from Polana Raspberry (Rubus idaeus L.) Fruit and Juice-In Vitro Study. 3003 97


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