Inhibition of growth and increase of alkaline phosphatase activity in cultured human oral cancer cells by all-trans retinoic acid

Xiao, Bingxiu; Guo, Junming; Lou, Yang; Meng, Di; Zhao, Wenxuan; Zhang, L.; Yan, Chunhong; Wang, Dandan

doi:10.1016/j.ijom.2006.01.005

Cited by 17 publications

(14 citation statements)

References 23 publications

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“…RA has been previously shown to promote growth inhibition of OSCC cell lines such as SCC‐15, SCC‐25, and KB. A number of studies have shown that OSCC growth inhibition by atRA is principally related to cell‐cycle arrest during G1 phase, does not involve induction of apoptosis or cell death, and is accompanied by an increase in cytokeratin 13 expression and alkaline phosphatase activity, suggesting that RA induces cell differentiation [Yang et al, 2001; Kuroda et al, 2005; Xiao et al, 2006; Zhao et al, 2009]. In the present work, SCC‐25 cells exhibited a growth inhibition rate of ∼42% after 7 days of RA treatment, consistent with previous reports from our laboratory [Le et al, 2000, 2002].…”

Section: Discussionmentioning

confidence: 99%

Expression of homeobox genes in oral squamous cell carcinoma cell lines treated with all‐trans retinoic acid

Acquafreda

Nunes

Soprano

et al. 2010

J of Cellular Biochemistry

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Oral squamous cell carcinoma (OSCC) may arise from potentially malignant oral lesions. All-trans retinoic acid (atRA), which plays a role in cell growth and differentiation, has been studied as a possible chemotherapeutic agent in the prevention of this progression. While the mechanism by which atRA suppresses cell growth has not been completely elucidated, it is known that homeobox genes are atRA targets. To determine if these genes are involved in the atRA-mediated OSCC growth inhibition, PCR array was performed to evaluate the expression of 84 homeobox genes in atRA-sensitive SCC-25 cells compared to atRA-resistant SCC-9 cells following 7 days with atRA treatment. Results showed that the expression of 8 homeobox genes was downregulated and expression of 4 was upregulated in SCC-25 cells but not in SCC-9 cells. Gene expression levels were confirmed for seven of these genes by RT-qPCR. Expression of three genes that showed threefold downregulation was evaluated in SCC-25 cells treated with atRA for 3, 5, and 7 days. Three different patterns of atRA-dependent gene expression were observed. ALX1 showed downregulation only on day 7. DLX3 showed reduced expression on day 3 and further reduced on day 7. TLX1 showed downregulation only on days 5 and 7. Clearly the expression of homeobox genes is modulated by atRA in OSCC cell lines. However, the time course of this modulation suggests that these genes are not direct targets of atRA mediating OSCC growth suppression. Instead they appear to act as downstream effectors of atRA signaling.

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Section: Discussionmentioning

confidence: 99%

Expression of homeobox genes in oral squamous cell carcinoma cell lines treated with all‐trans retinoic acid

Acquafreda

Nunes

Soprano

et al. 2010

J of Cellular Biochemistry

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“…In the same study, it was also shown that DNA fragmentation was not observed in Jurkat cells (human T‐cell lymphoblast‐like cell line) in the presence or absence of ATRA. A recent investigation has shown that ATRA did not induce DNA fragmentation in human oral cancer cells, suggesting that DNA fragmentation by ATRA is cell type specific (Xiao et al ., ).…”

Section: Discussionmentioning

confidence: 99%

DNA fragmentation induced by all‐trans retinoic acid and its steroidal analogue EA‐4 in C₂C₁₂ mouse and HL‐60 human leukemic cells in vitro

Alakhras

Stephanou

Demopoulos

et al. 2013

J of Applied Toxicology

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We have recently shown that retinoic acid induces micronucleation mainly via chromosome breakage (Alakhras et al. Cancer Lett 2011; 306: 15-26). To further study retinoic acid clastogenicity and evaluate DNA damaging potential we investigated the ability of (a) all-trans retinoic acid and its steroidal analogue EA-4 to induce DNA fragmentation by using Comet assay under alkaline unwinding and neutral condition electrophoresis, and (b) the retinoids under study to induce small (0-1 kb) DNA fragments. Two cell lines, C2C12 mouse cells and HL-60 human leukemic cells were used in this study. We found that all-trans retinoic acid and its steroidal analogue EA-4 (a) provoke DNA migration due to DNA fragmentation as it is shown by the increased values of Comet parameters, and (b) induce significantly small-size fragmented genomic DNA as indicated by the quantification of necrotic/apoptotic small DNA segments in both cell systems. A different response between the two cell lines was observed in relation to retinoid ability to increase the percentage of DNA in the tail as well as break DNA in to small fragments. Our findings confirm the ability of retinoic acid to provoke micronucleation by disrupting DNA into fragments, among which small pieces of double-stranded DNA up to 1 kb are identified.

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“…However, the precise mechanism underlying the anti-tumor effect of ATRA is not yet fully understood. Previous studies have shown that OSCC growth inhibition by ATRA is mainly related to cell cycle arrest, cell apoptosis, and differentiation (10,11). Recently, Frank et al (12) reported that human tongue squamous cell carcinoma cells were deficient in Cx43 expression.…”

Section: Introductionmentioning

confidence: 99%

All-trans retinoic acid restores gap junctional intercellular communication between oral cancer cells with upregulation of Cx32 and Cx43 expressions in vitro

Wang¹,

Dai²,

Huang³

et al. 2013

Med Oral

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Objective: All-trans retinoic acid (ATRA) has been demonstrated to inhibit tumor growth by restoration of gap junctional intercellular communication (GJIC) via upregulation of connexin (Cx) expression in some solid tumors. However, the relationship between ATRA and GJIC remains unclear in oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the effect of ATRA on the GJIC function of OSCC. Study design: We measured the effects of ATRA on the viability and cell cycle distribution of SCC9 and Tca8113 OSCC cells. The GJIC function was observed using the scrape-loading dye transfer technique, and the mRNA and protein levels of Cx32 and Cx43 were detected by qRT-PCR, Western blot, and immunofluorescence assays. Results: ATRA inhibited the growth of OSCC cells in a dose- and time-dependent manner (P <0.05) and caused cell cycle arrest. ATRA-treated cells showed a 2.69-fold and 2.06-fold enhancement of GJIC in SCC9 and Tca8113 cells, respectively (P <0.05). Moreover, ATRA induced upregulation of Cx32 and Cx43 at both the mRNA and protein levels in OSCC cells. Conclusion: Our results indicated that restoration of GJIC via enhanced Cx32 and Cx43 expression might serve as a novel mechanism for the anti-tumor effect of ATRA in OSCC. Key words:All-trans retinoic acid, oral squamous cell carcinoma, connexin, gap junctional intercellular communication.

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Inhibition of growth and increase of alkaline phosphatase activity in cultured human oral cancer cells by all-trans retinoic acid

Cited by 17 publications

References 23 publications

Expression of homeobox genes in oral squamous cell carcinoma cell lines treated with all‐trans retinoic acid

Expression of homeobox genes in oral squamous cell carcinoma cell lines treated with all‐trans retinoic acid

DNA fragmentation induced by all‐trans retinoic acid and its steroidal analogue EA‐4 in C₂C₁₂ mouse and HL‐60 human leukemic cells in vitro

All-trans retinoic acid restores gap junctional intercellular communication between oral cancer cells with upregulation of Cx32 and Cx43 expressions in vitro

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Inhibition of growth and increase of alkaline phosphatase activity in cultured human oral cancer cells by all-trans retinoic acid

Cited by 17 publications

References 23 publications

Expression of homeobox genes in oral squamous cell carcinoma cell lines treated with all‐trans retinoic acid

Expression of homeobox genes in oral squamous cell carcinoma cell lines treated with all‐trans retinoic acid

DNA fragmentation induced by all‐trans retinoic acid and its steroidal analogue EA‐4 in C2C12 mouse and HL‐60 human leukemic cells in vitro

All-trans retinoic acid restores gap junctional intercellular communication between oral cancer cells with upregulation of Cx32 and Cx43 expressions in vitro

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DNA fragmentation induced by all‐trans retinoic acid and its steroidal analogue EA‐4 in C₂C₁₂ mouse and HL‐60 human leukemic cells in vitro