Advanced progress on the relationship between RA and its receptors and malignant tumors

Li, Molin; Sun, Yuqiang; Guan, Xingfang; Shu, Xiaohong; Li, Chuangang

doi:10.1016/j.critrevonc.2014.04.001

Cited by 15 publications

(11 citation statements)

References 99 publications

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“…ATRA is the first example of a clinically useful cyto-differentiating agent to be used in the treatment of acute promyelocytic leukemia (23). Now it is proposed as an antitumor agent not only in the context of hematological malignancies but also the chemo-prevention and treatment of many cancers including HCC (8)(9)(10)(11). In addition, it has been reported that ATRA could be used as a chemopreventive agent to inhibit the progression of premalignant lesions of the breast (24,25).…”

Section: Discussionmentioning

confidence: 99%

“…All-trans retinoic acid (ATRA), as a predominant natural metabolite of vitamin A, is involved in many important biological processes, including vision, morphogenesis, differentiation, growth, metabolism, and cellular homeostasis (7). ATRA is currently used to induce remission in patients with acute promyelocytic leukemia and has the potential for use in the treatment of solid tumors including HCC (8)(9)(10)(11). Many studies have reported that ATRA has anti-HCC ability.…”

Section: Introductionmentioning

confidence: 99%

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All-trans retinoic acid inhibits proliferation, migration, invasion and induces differentiation of hepa1-6 cells through reversing EMT in vitro

Cui

Gong

et al. 2015

International Journal of Oncology

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Hepatocellular carcinoma (HCC) has the characristics of tumor invasiveness, frequent intrahepatic spread and extra hepatic metastases, which affects the therapy efficiency and prognosis. Epithelial-mesenchymal transition (EMT) is now recognized as a key process in tumor invasion, metastasis and the generation of cancer initiating cells. All-trans retinoic acid (ATRA) is currently used as a potential chemo-therapeutic or chemo-preventive agent because of its anti-proliferative, pro-apoptotic and antioxidant properties. This study investigated the effects of ATRA at different concentrations on the proliferation, migration, invasion, differentiation and functions of the mouse hepa1-6 hepatocarcinoma cell line and explored whether ATRA regulates EMT in the antitumor process. Trypan blue staining and colony formation assay were used to detect cell proliferation. Wound-healing assay and Transwell Matrigel assay were performed to examine migration. Invasion was assessed by using Transwell invasion assay. In the present study, ATRA significantly inhibited the cell growth, colony formation, migration, and invasion capability of hepa1-6 cells in a dose-dependent manner. Furthermore, ATRA at low concentration (0.1 µmol/l) could generate these influences. After treated in the ATRA medium, the expression of mature hepatic markers ALB (albumin), CK18 (cytokeratin 18), TAT (tyrosine aminotransferase), ApoB (apolipoprotein B) decreased and that of hepatocarcinoma marker AFP (α fetoprotein) increased. At day 7 after ATRA induction, hepa1-6 cells showed comparable indocyanine green (ICG) uptake and glycogen storage function to the blank control. The mRNA expression of mesenchymal markers N-cadherin, vimentin, snail and twist decreased, while expression of epithelial marker E-cadherin increased in hepa1-6 cells after treated with ATRA. Therefore, this study demonstrates that ATRA remarkably suppressed the proliferation, migration, invasion of hepa1-6 hepatocarcinoma cell line and effectively induced its differentiation and liver functions in vitro through the reversal of EMT. HCC may be more sensitive to ATRA than other cancers, suggesting the prospective usefulness of ATRA in the treatment of HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

All-trans retinoic acid inhibits proliferation, migration, invasion and induces differentiation of hepa1-6 cells through reversing EMT in vitro

Cui

Gong

et al. 2015

International Journal of Oncology

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“…Retinoids are already used in the treatment of epithelial cancer and promyelocytic leukemia [ 19 ; 39 – 42 ] and discussed for the therapy and / or chemoprevention of breast and gastric cancer [ 35 ; 43 ] as well as neuroblastoma [ 39 ]. The mechanisms of RA in cancer treatment include inhibition of cell proliferation, promotion of terminal tumor cell differentiation and induction of apoptosis [ 9 ]. It has been shown that RA has profound effects on cell growth and cause apoptosis in diverse tumor cells [ 1 ; 2 ; 44 ].…”

Section: Discussionmentioning

confidence: 99%

“…Due to their regulatory potential, RARs and RXRs are major drug targets for a variety of pathologies, including cancer. Each subtype of RARs has been implicated in the regulation of cancer development and the anticancer activities of retinoids [ 9 ]. RARß is a tumor suppressor gene [ 10 ] and the best characterized RA responsive receptor with a confirmed ßRARE binding site.…”

Section: Introductionmentioning

confidence: 99%

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Additive Effects of Retinoic Acid (RA) and Bone Morphogenetic Protein 4 (BMP-4) Apoptosis Signaling in Retinoblastoma Cell Lines

et al. 2015

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Retinoids have been shown to serve promising therapeutic agents for human cancers, e.g. the treatment of neuroblastoma. Synthetic retinoids, specific for particular retinoic acid (RA) receptors, are tested as new therapy strategies. In the present study, application of recombinant retinoic acid (RA) lowers retinoblastoma (RB) cell viability and induces apoptosis in RB cell lines. Combined treatment of RA and bone morphogenetic protein 4 (BMP-4) increases the pro-apoptotic effect of RA in the RB cells lines WERI-Rb1, Y-79, RB355, RBL-30 and RBL-15, indicating an additive effect. We could show that in WERI-Rb1 cells RA/BMP-4 mediated cell death is at least partially caspase-dependent, whereby RA and BMP-4 additively increased (i) Apaf-1 mRNA levels, (ii) caspase-9 cleavage activity and (iii) the number of activated, cleaved caspase-3 positive cells. Compared to single application of RA and BMP-4, combined RA/BMP-4 treatment significantly augments mRNA levels of the retinoic acid receptors (RARs) RARα and RARß and the retinoic X receptor (RXR) RXRγ suggesting an interaction in the induction of these RA receptor subtypes in WERI-Rb1 cells. Agonist studies revealed that both, RARs and RXRs are involved in RA/BMP-4 mediated apoptosis in WERI-Rb1 retinoblastoma cells. Employing specific RAR subtype antagonists and a RXRß and RXRγ knockdown, we proved that RA/BMP-4 apoptosis signaling in WERI-Rb1 cells requires the RA receptor subtypes RARα, RARß, RXRß and RXRγ. Deciphering signaling mechanisms underlying apoptosis induction of RA and BMP-4 in WERI-Rb1 cells, our study provides useful starting-points for future retinoid-based therapy strategies in retinoblastoma.

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Histone Deacetylase Inhibitor Tributyrin and Vitamin A in Cancer

Heidor¹,

Vargas-Mendez²,

Moreno³

2017

Handbook of Nutrition, Diet, and Epigenetics

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Advanced progress on the relationship between RA and its receptors and malignant tumors

Cited by 15 publications

References 99 publications

All-trans retinoic acid inhibits proliferation, migration, invasion and induces differentiation of hepa1-6 cells through reversing EMT in vitro

All-trans retinoic acid inhibits proliferation, migration, invasion and induces differentiation of hepa1-6 cells through reversing EMT in vitro

Additive Effects of Retinoic Acid (RA) and Bone Morphogenetic Protein 4 (BMP-4) Apoptosis Signaling in Retinoblastoma Cell Lines

Histone Deacetylase Inhibitor Tributyrin and Vitamin A in Cancer

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