Molecular mechanism of inhibitory effects of C-phycocyanin combined with all-trans-retinoic acid on the growth of HeLa cells in vitro

Tumor Biology ◽  
2014 ◽  
Vol 35 (6) ◽  
pp. 5619-5628 ◽  
Author(s):  
Fan Yang ◽  
Bing Li ◽  
Xian-Ming Chu ◽  
Cong-Yi Lv ◽  
Ying-Jie Xu ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Molecular Mechanism ◽  
Hela Cells ◽  
Inhibitory Effects ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Enhanced Oral Absorption of All-trans Retinoic Acid upon Encapsulation in Solid Lipid Nanoparticles

2020 ◽  
Vol 8 (6) ◽  
pp. 495-510
Author(s):  
Manoj Kumar ◽  
Garima Sharma ◽  
Dinesh Singla ◽  
Sukhjeet Singh ◽  
Vandita Kakkar ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Side Effects ◽  
Solid Lipid Nanoparticles ◽  
In Vitro Release ◽  
Lipid Nanoparticles ◽  
Solid Lipid ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Vitro Release

Background:: All-trans retinoic acid (ATRA) is widely employed in the treatment of various proliferative and inflammatory diseases. However, its therapeutic efficacy is imperiled due to its poor solubility and stability. Latter was surmounted by its incorporation into a solid matrix of lipidic nanoparticles (SLNs). Methods:: ATRA loaded SLNs (ATRA-SLNs) were prepared using a novel microemulsification technique (USPTO 9907758) and an optimal composition and were characterized in terms of morphology, differential scanning calorimetry (DSC), and powder X-ray diffraction studies (PXRD). In vitro release, oral plasma pharmacokinetics (in rats) and stability studies were also done. Results:: Rod-shaped ATRA-SLNs could successfully incorporate 3.7 mg/mL of ATRA, increasing its solubility (from 4.7 μg/mL) by 787 times, having an average particle size of 131.30 ± 5.0 nm and polydispersibility of 0.283. PXRD, DSC, and FTIR studies confirmed the formation of SLNs. Assay/total drug content and entrapment efficiency of ATRA-SLNs was 92.50 ± 2.10% and 84.60 ± 3.20% (n=6), respectively, which was maintained even on storage for one year under refrigerated conditions as an aqueous dispersion. In vitro release in 0.01 M phosphate buffer (pH 7.4) with 3% tween 80 was extended 12 times from 2h for free ATRA to 24 h for ATRA-SLNs depicting Korsmeyer Peppas release. Oral administration in rats showed 35.03 times enhanced bioavailability for ATRA-SLNs. Conclusion:: Present work reports preparation and evaluation of bioenhanced ATRA-SLNs containing a high concentration of ATRA (>15 times than that reported by others). Latter is attributed to the novel preparation process and intelligent selection of components. Lay Summary: All-trans retinoic acid (ATRA) shows an array of pharmacological activities but its efficacy is limited due to poor solubility, stability and side effects. In present study its solubility and efficacy is improved by 787 and 35.5 times, respectively upon incorporation into solid lipid nanoparticles (ATRA-SLNs). Latter extended its release by 12 times and provided stability for at least a year under refrigeration. A controlled and sustained release will reduce dose related side effects. ATRA-SLNs reported presently can thus be used in treatment /prophylaxis of disorders like cancers, tuberculosis, age related macular degeneration and acne and as an immune-booster.

scholarly journals All-Trans Retinoic Acid Increases DRP1 Levels and Promotes Mitochondrial Fission

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1202
Author(s):  
Bojjibabu Chidipi ◽  
Syed Islamuddin Shah ◽  
Michelle Reiser ◽  
Manasa Kanithi ◽  
Amanda Garces ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Mitochondrial Fission ◽  
Normal Function ◽  
Mitochondrial Network ◽  
Protein Levels ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Area And Perimeter

In the heart, mitochondrial homeostasis is critical for sustaining normal function and optimal responses to metabolic and environmental stressors. Mitochondrial fusion and fission are thought to be necessary for maintaining a robust population of mitochondria, and disruptions in mitochondrial fission and/or fusion can lead to cellular dysfunction. The dynamin-related protein (DRP1) is an important mediator of mitochondrial fission. In this study, we investigated the direct effects of the micronutrient retinoid all-trans retinoic acid (ATRA) on the mitochondrial structure in vivo and in vitro using Western blot, confocal, and transmission electron microscopy, as well as mitochondrial network quantification using stochastic modeling. Our results showed that ATRA increases DRP1 protein levels, increases the localization of DRP1 to mitochondria in isolated mitochondrial preparations. Our results also suggested that ATRA remodels the mitochondrial ultrastructure where the mitochondrial area and perimeter were decreased and the circularity was increased. Microscopically, mitochondrial network remodeling is driven by an increased rate of fission over fusion events in ATRA, as suggested by our numerical modeling. In conclusion, ATRA results in a pharmacologically mediated increase in the DRP1 protein. It also results in the modulation of cardiac mitochondria by promoting fission events, altering the mitochondrial network, and modifying the ultrastructure of mitochondria in the heart.

scholarly journals Growth Inhibitory Effects of Ester Derivatives of Menahydroquinone-4, the Reduced Form of Vitamin K2(20), on All-Trans Retinoic Acid-Resistant HL60 Cell Line

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 758
Author(s):  
Hirofumi Yamakawa ◽  
Shuichi Setoguchi ◽  
Shotaro Goto ◽  
Daisuke Watase ◽  
Kazuki Terada ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Adverse Effects ◽  
Vitamin K2 ◽  
Reduced Form ◽  
Inhibitory Effects ◽  
Hl60 Cells ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Growth Inhibitory ◽  
Derivatives Of

The first-choice drug for acute promyelocytic leukemia (APL), all-trans retinoic acid (ATRA), frequently causes drug-resistance and some adverse effects. Thus, an effective and safe agent for ATRA-resistant APL is needed. Menaquinone-4 (MK-4, vitamin K2(20)), used for osteoporosis treatment, does not have serious adverse effects. It has been reported that MK-4 has growth-inhibitory effects on HL60 cells by inducing apoptosis via the activation of Bcl-2 antagonist killer 1 (BAK). However, the effect of MK-4 on ATRA-resistant APL has not been reported. Here, we show that ester derivatives of menahydroquinone-4 (MKH; a reduced form of MK-4), MKH 1,4-bis-N,N-dimethylglycinate (MKH-DMG) and MKH 1,4-bis-hemi-succinate (MKH-SUC), exerted strong growth-inhibitory effects even on ATRA-resistant HL60 (HL-60R) cells compared with ATRA and MK-4. MKH delivery after MKH-SUC treatment was higher than that after MK-4 treatment, and the results indicated apoptosis induced by BAK activation. In contrast, for MKH-DMG, reconversion to MKH was slow and apoptosis was not observed. We suggest that the ester forms, including monoesters of MKH-DMG, exhibit another mechanism independent of apoptosis. In conclusion, the MKH derivatives (MKH-SUC and MKH-DMG) inhibited not only HL60 cells but also HL-60R cells, indicating a potential to overcome ATRA resistance.

Differential regulation of GPI‐linked molecules on leukaemic promyelocytes treated in vitro with all‐ trans retinoic acid

1996 ◽  
Vol 93 (2) ◽  
pp. 392-393 ◽  
Author(s):  
R. DI NOTO ◽  
E. M. SCHIAVONE ◽  
C. LO PARDO ◽  
F. FERRARA ◽  
C. MANZO ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Differential Regulation ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

scholarly journals Fucoidan enhances the therapeutic potential of arsenic trioxide and all-trans retinoic acid in acute promyelocytic leukemia, in vitro and in vivo

Oncotarget ◽  
2016 ◽  
Vol 7 (29) ◽  
pp. 46028-46041 ◽  
Author(s):  
Farzaneh Atashrazm ◽  
Ray M. Lowenthal ◽  
Joanne L. Dickinson ◽  
Adele F. Holloway ◽  
Gregory M. Woods
Keyword(s):  
Retinoic Acid ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Therapeutic Potential ◽  
Promyelocytic Leukemia ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

MDI 301 suppresses myeloid leukemia cell growth in vitro and in vivo without the toxicity associated with all-trans retinoic acid therapy

2015 ◽  
Vol 26 (7) ◽  
pp. 763-773
Author(s):  
Muhammad N. Aslam ◽  
Shannon McClintock ◽  
Shazli P. Khan ◽  
Patricia Perone ◽  
Ronald Allen ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Cell Growth ◽  
Myeloid Leukemia ◽  
Leukemia Cell ◽  
Acid Therapy ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Myeloid Leukemia Cell

Developmental role of endogenous retinoids in the determination of morphallactic field in budding tunicates

Development ◽  
1993 ◽  
Vol 117 (3) ◽  
pp. 835-845 ◽  
Author(s):  
K. Kawamura ◽  
K. Hara ◽  
S. Fujiwara
Keyword(s):  
Retinoic Acid ◽  
Aldehyde Dehydrogenase ◽  
Ectopic Expression ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Proximal Extremity ◽  
Developmental Role

We have extracted retinoids from the budding tunicate Polyandrocarpa misakiensis and, using HPLC, identified some major peaks as cis-retinal, all-trans-retinal and all-trans-retinoic acid, of which cis-retinal was most abundant (~2 micromolar). In developing buds, the amount of cis-retinal was about one-fifth that of the adult animals. In those buds, aldehyde dehydrogenase, which could metabolize retinal in vitro, was expressed in epithelial cells and then in mesenchymal cells at the proximal extremity, that is, the future developmental field of the bud. Exogenous retinoic acid comparable to the endogenous level could induce an additional field at the distal end of the bud, resulting in a double monster. The induction always accompanied an ectopic expression of aldehyde dehydrogenase. The results of this work suggest that retinoic acid or related molecule(s) act as an endogenous trigger of morphallactic development of Polyandrocarpa buds.

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