scholarly journals All-Trans Retinoic Acid Enhances Chemosensitivity to 5-FU by Targeting miR-378c/E2F7 Axis in Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Ji Li ◽  
Qing Xiang ◽  
Mei Wang ◽  
Hongchang Zhang ◽  
Rong Liang
Keyword(s):  
Retinoic Acid ◽  
Molecular Mechanisms ◽  
Vital Role ◽  
Luciferase Reporter ◽  
Inhibitory Effects ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Diphenyltetrazolium Bromide ◽  
Life Threatening ◽  
Hct116 Cells

Colorectal carcinoma (CRC), a life-threatening malignancy, has been found to present resistance to 5-fluorouracil (5-FU) and cause a poor prognosis for patients. Previous studies have proved that all-trans retinoic acid (ATRA) could inhibit the development of CRC cells. In addition, miR-378c was discovered to exert a vital role in various cancers. In this study, we utilized MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), transwell assay, and flow cytometry to confirm that ATRA was able to enhance the inhibitory effects of 5-FU on HCT116 cells effectively by promoting cell apoptosis. Then, ENCORI database (http://starbase.sysu.edu.cn/) was employed to predict that miR-378c was downregulated dramatically in CRC and E2F7 was the direct target of miR-378c. QRT-PCR (quantitative real-time polymerase chain reaction) was conducted to verify that the expression level of miR-378c was decreased while E2F7 expression was upregulated in CRC tissues compared with para-carcinoma tissues. Additionally, treatment of 5-FU combined with ATRA could increase miR-378c expression, whereas it decreased the expression of E2F7. Dual-Luciferase Reporter assay results revealed that miR-378c could regulate the load of E2F7 by binding to its 3′UTR directly. Furthermore, miR-378c inhibitor or vector with E2F7 partially counteracted the effects of 5-FU combined with ATRA on viability, migration, invasion, and apoptosis of HCT116 cells. In conclusion, our study aims to confirm that ATRA enhances chemosensitivity to 5-FU of patients with CRC and expound the potential molecular mechanisms.

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.

scholarly journals Massive pulmonary embolism at the onset of acute promyelocytic leukemia

2016 ◽  
Vol 8 ◽  
pp. 2016027 ◽  
Author(s):  
Federica Sorà ◽  
Patrizia Chiusolo ◽  
Luca Laurenti
Keyword(s):  
Pulmonary Embolism ◽  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Massive Pulmonary Embolism ◽  
Promyelocytic Leukemia ◽  
Early Complication ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
First Case ◽  
Life Threatening

Life-threatening bleeding is a major and early complication of acute promyelocytic leukemia (APL), but in the last years there is a growing evidence of thromboses in  APL. We report the first case of a young woman with dyspnea as the first symptom of APL due to massive pulmonary embolism (PE) successfully treated with thrombolysis for PE and heparin. APL has been processed with a combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) obtaining complete remission.

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

scholarly journals Interleukin 10 abolishes the growth inhibitory effects of all-trans retinoic acid on human myeloma cells

2002 ◽  
Vol 116 (4) ◽  
pp. 787-795 ◽  
Author(s):  
Takemi Otsuki ◽  
Kenichiro Yata ◽  
Haruko Sakaguchi ◽  
Junichi Kurebayashi ◽  
Yoshinobu Matsuo ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Interleukin 10 ◽  
Inhibitory Effects ◽  
Myeloma Cells ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Growth Inhibitory ◽  
Human Myeloma Cells

scholarly journals From an old remedy to a magic bullet: molecular mechanisms underlying the therapeutic effects of arsenic in fighting leukemia

Blood ◽  
2011 ◽  
Vol 117 (24) ◽  
pp. 6425-6437 ◽  
Author(s):  
Sai-Juan Chen ◽  
Guang-Biao Zhou ◽  
Xiao-Wei Zhang ◽  
Jian-Hua Mao ◽  
Hugues de Thé ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Molecular Mechanisms ◽  
Promyelocytic Leukemia ◽  
Magic Bullet ◽  
Therapeutic Effects ◽  
New Paradigm ◽  
Therapeutic Benefits ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract Arsenic had been used in treating malignancies from the 18th to mid-20th century. In the past 3 decades, arsenic was revived and shown to be able to induce complete remission and to achieve, when combined with all-trans retinoic acid and chemotherapy, a 5-year overall survival of 90% in patients with acute promyelocytic leukemia driven by the t(15;17) translocation-generated promyelocytic leukemia–retinoic acid receptor α (PML-RARα) fusion. Molecularly, arsenic binds thiol residues and induces the formation of reactive oxygen species, thus affecting numerous signaling pathways. Interestingly, arsenic directly binds the C3HC4 zinc finger motif in the RBCC domain of PML and PML-RARα, induces their homodimerization and multimerization, and enhances their interaction with the SUMO E2 conjugase Ubc9, facilitating subsequent sumoylation/ubiquitination and proteasomal degradation. Arsenic-caused intermolecular disulfide formation in PML also contributes to PML-multimerization. All-trans retinoic acid, which targets PML-RARα for degradation through its RARα moiety, synergizes with arsenic in eliminating leukemia-initiating cells. Arsenic perturbs a number of proteins involved in other hematologic malignancies, including chronic myeloid leukemia and adult T-cell leukemia/lymphoma, whereby it may bring new therapeutic benefits. The successful revival of arsenic in acute promyelocytic leukemia, together with modern mechanistic studies, has thus allowed a new paradigm to emerge in translational medicine.

scholarly journals All-trans-retinoic acid-mediated cytoprotection in LLC-PK1 renal epithelial cells is coupled to p-ERK activation in a ROS-independent manner

2017 ◽  
Vol 313 (6) ◽  
pp. F1200-F1208 ◽  
Author(s):  
Jessica M. Sapiro ◽  
Terrence J. Monks ◽  
Serrine S. Lau
Keyword(s):  
Cell Death ◽  
Retinoic Acid ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Independent Manner ◽  
Toxicant Exposure ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Survival Pathways

Although all- trans-retinoic acid (ATRA) provides protection against a variety of conditions in vivo, particularly ischemia, the molecular mechanisms underpinning these effects remain unclear. The present studies were designed to assess potential mechanisms by which ATRA affords cytoprotection against renal toxicants in LLC-PK1 cells. Pretreatment of LLC-PK1 cells with ATRA (25 μM) for 24 h afforded cytoprotection against oncotic cell death induced by p-aminophenol (PAP), 2-(glutathion- S-yl)hydroquinone (MGHQ), and iodoacetamide but not against apoptotic cell death induced by cisplatin. Inhibition of protein synthesis with cycloheximide blunted ATRA protection, indicating essential cell survival pathways must be engaged before toxicant exposure to provide cytoprotection. Interestingly, ATRA did not prevent the PAP-induced generation of reactive oxygen species (ROS) nor did it alter glutathione levels. Moreover, ATRA had no significant effect on Nrf2 protein expression, and the Nrf2 inducers sulforaphane and MG132 did not influence ATRA cytoprotection, suggesting cytoprotective pathways beyond those that influence ROS levels contribute to ATRA protection. In contrast, ATRA rapidly (15 min) induced levels of the cellular stress kinases p-ERK and p-AKT at concentrations of ATRA (10 and 25 μM) required for cytoprotection. Consistent with a role for p-ERK in ATRA-mediated cytoprotection, inhibition of p-ERK with PD98059 reduced the ability of ATRA to afford protection against PAP toxicity. Collectively, these data suggest that p-ERK and its downstream targets, independent of ROS and antioxidant signaling, are important contributors to the cytoprotective effects of ATRA against oncotic cell death.

scholarly journals Multiple adverse drug reactions during all-trans retinoic acid treatment for acute promyelocytic leukemia: differentiation syndrome, bradycardia, intestinal necrosis

2020 ◽  
Vol 1 (2) ◽  
pp. 109-116
Author(s):  
Valeria Ferla ◽  
Mariarita Sciumé ◽  
Umberto Gianelli ◽  
Luca Baldini ◽  
Nicola Stefano Fracchiolla
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Adverse Drug Reactions ◽  
Leukocytoclastic Vasculitis ◽  
Promyelocytic Leukemia ◽  
Drug Reactions ◽  
Intestinal Necrosis ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Life Threatening

Abstract All-trans retinoic acid (ATRA) induces complete remission in a high proportion of acute promyelocytic leukemia (APL). Nevertheless it is be associated with adverse drug reactions that might be life-threatening including differentiation syndrome, myocarditis, myositis, Sweet’s syndrome and ulcers. We describe a case of APL who during induction therapy developed ATRA syndrome, cardiac arrhythmia and multiple episodes of intestinal necrosis that required surgery. In particular, we report here for the first intestinal necrosis attributable to ATRA treatment in the absence of histological evidence of promyelocytes infiltration or leukocytoclastic vasculitis. Keywords Acute promyelocytic leukemia, all-trans retinoic acid, adverse drug reaction

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