Boswellic acid induces epigenetic alterations by modulating DNA methylation in colorectal cancer cells

Yan, Siyu; Takahashi, Masanobu; Byun, Hyang‐Min; Link, Alexander; Sharma, Nupur; Balaguer, Francesc; Leung, Hon Chiu Eastwood; Boland, C. Richard; Goel, Ajay

doi:10.4161/cbt.19604

Cited by 60 publications

(42 citation statements)

References 44 publications

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“…Baisch showed that Ki-67 level elevated in tumor cells after cytokine-induced apoptosis (32). In contrast to our findings, some investigations demonstrated that Frankincense had a more obvious anti-proliferative effect than apoptosis induction effect on colorectal cancer cell line (11).…”

Section: Discussioncontrasting

confidence: 54%

The Effects of Frankincense on Oral Squamous Cell Carcinoma Cell Line

Jaafari‐Ashkavandi¹,

Hamedi²,

Assar³

et al. 2017

Int J Cancer Manag

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Background: Cytotoxic effects of Frankincense resin have been shown on some cancer cell lines. Due to its low side effects, this study was designed to evaluate the anticancer properties of water soluble elements of Frankincense oleo-gum-resin on human oral squamous cell carcinoma cell line. Methods:Oleo-gum-resin was macerated in ethanol. After filtration, the water soluble fraction of dried residue was extracted. KB cells were treated with 0, 62.5, 125, 250 and 500 µg/mL concentrations of obtained Frankincense aqueous fractions and with Doxorubicin as positive control. Frankincense induced cell cytotoxicity; apoptosis and proliferation were investigated using WST assay, Annexin V-FITC/PI, and Ki-67 staining, respectively. Data were analyzed using Kruskal-Wallis test by SPSS 17 software.Results: IC50 of 137.21 µg/mL was obtained from Frankincense aqueous fraction after 48 hours. The percentage of apoptotic cells was elevated in a time-and dose-dependent manner. There was no statistical difference in the Ki-67 expression of KB cells, using different concentration of Frankincense aqueous fraction after 24 and 48 hours (P = 0.083). Doxorubicin inhibited cells growth essentially through apoptosis. Conclusions:Frankincense aqueous fractions seem to suppress KB cell growth through the induction of apoptosis and necrosis rather than the inhibition of proliferation and hence might be a potential anticancer agent. Structural analysis and purification of potent components are suggested for determining more definitive results.

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Section: Discussioncontrasting

confidence: 54%

The Effects of Frankincense on Oral Squamous Cell Carcinoma Cell Line

Jaafari‐Ashkavandi¹,

Hamedi²,

Assar³

et al. 2017

Int J Cancer Manag

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“…SAMD14 SNPs are associated with blood platelet volume (Fehrmann et al, 2011), and SAMD14 is downregulated and differentially methylated in cancers (Shen et al, 2012a; Sun et al, 2008). GATA-2 function through Samd14 +2.5 controls myelo-erythroid progenitors and erythroid precursor cell maturation/function (Figure 7C).…”

Section: Discussionmentioning

confidence: 99%

Hematopoietic Signaling Mechanism Revealed from a Stem/Progenitor Cell Cistrome

et al. 2015

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SUMMARY Thousands of cis-elements in genomes are predicted to have vital functions. While conservation, activity in surrogate assays, polymorphisms, and disease mutations provide functional clues, deletion from endogenous loci constitutes the gold-standard test. A GATA-2-binding, Gata2 intronic cis-element (+9.5) required for hematopoietic stem cell genesis in mice is mutated in a human immunodeficiency syndrome. As +9.5 is the only cis-element known to mediate stem cell genesis, we devised a strategy to identify functionally comparable enhancers (“+9.5-like”) genome-wide. Gene editing revealed +9.5-like activity to mediate GATA-2 occupancy, chromatin opening, and transcriptional activation. A +9.5-like element resided in Samd14, which encodes a protein of unknown function. Samd14 increased hematopoietic progenitor levels/activity, promoted signaling by a pathway vital for hematopoietic stem/progenitor cell regulation (Stem Cell Factor/c-Kit), and c-Kit rescued Samd14 loss-of-function phenotypes. Thus, the hematopoietic stem/progenitor cell cistrome revealed a mediator of a signaling pathway that has broad importance for stem/progenitor cell biology.

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“…SMPD3 has also been implicated in cell growth inhibition and tumorigenesis (17). The promoter of SMPD3 was identified by hypermethylation in breast and colorectal cancer cells (18,19). The identification was based on high throughput screening; however, the methylation status in ccRCC has not been reported to date.…”

Section: Discussionmentioning

confidence: 99%

Abnormal methylation status of FBXW10 and SMPD3, and associations with clinical characteristics in clear cell renal cell carcinoma

Wang

et al. 2015

Oncology Letters

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Abstract. The present study aimed to evaluate the use of the 27K methylation array to investigate abnormal methylation of two genes and their associations with clinical characteristics in clear cell renal cell carcinoma (ccRCC). Six differentially-methylated genes identified using the 27K methylation array were screened in the human RCC 786-0 cell line and normal kidney tissues by bisulfite sequencing polymerase chain reaction (PCR). Differentially-methylated regions (DMRs) that were abnormally hypermethylated in the cell line were further validated in renal tumor and paired normal tissues by pyrosequencing. The correlations between DMRs and differences (methylation rate of tumor minus that of paired normal tissue) according to gender, age, tumor size, Fuhrman grade and disease stage were assessed. Gene expression prior to and following 5-Aza-2'-deoxycytidine treatment was examined using reverse transcription quantitative PCR (RT-qPCR). Two DMRs located in the FBXW10 and SMPD3 genes were found to be hypermethylated in the 786-0 cells, but not in the normal kidney tissues. Pyrosequencing results showed that the average methylation rate of FBXW10 in the cancer tissues was significantly higher compared to that in the paired normal tissues (48.78 vs. 34.62%; P<0.001). The methylation rate of SMPD3 was also higher in the cancer tissues compared with the paired normal tissues (58.98 vs. 38.66%; P<0.001). In stage T1 RCC, the methylation rate of the tumor tissue was positively correlated with the Fuhrman grade (P=0.02). The difference in methylation between the tumor and normal tissues was significantly higher in the group with high Fuhrman grade for the two genes. Furthermore, the linear correlation between methylation difference and tumor size was also confirmed (P=0.01). The RT-qPCR analysis demonstrated that SMPD3 and FBXW10 mRNA expression was significantly upregulated following 5-Aza-2'-deoxycytidine treatment. The results identified two novel DMRs located in SMPD3 and FBXW10 that were hypermethylated in the ccRCC tissue samples. The methylation profile in ccRCC could potentially provide predictive information for clinical decisions.

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Boswellic acid induces epigenetic alterations by modulating DNA methylation in colorectal cancer cells

Cited by 60 publications

References 44 publications

The Effects of Frankincense on Oral Squamous Cell Carcinoma Cell Line

The Effects of Frankincense on Oral Squamous Cell Carcinoma Cell Line

Hematopoietic Signaling Mechanism Revealed from a Stem/Progenitor Cell Cistrome

Abnormal methylation status of FBXW10 and SMPD3, and associations with clinical characteristics in clear cell renal cell carcinoma

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