Casticin inhibits the activity of transcription factor Sp1 and the methylation of RECK in MGC803 gastric cancer cells

Yang, Fan; He, Kefei; Huang, Li; Zhang, Lingyan; Liu, Aixue; Zhang, Jiren

doi:10.3892/etm.2016.4003

Cited by 13 publications

(9 citation statements)

References 45 publications

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“…Furthermore, we have reported that casticin was cytotoxic for cancer cells; decreased the total number of viable cells, induced cell cycle arrest, and apoptosis of SCC-4 cells in vitro. These findings are in agreement with other reports indicating that casticin suppresses the proliferation of different tumor cells (11,22,35,36). Importantly, casticin had no effects on cell proliferation and prolactin release in nonstimulated primary pituitary cells in vitro (17).…”

Section: Discussionsupporting

confidence: 93%

Casticin Inhibits In Vivo Growth of Xenograft Tumors of Human Oral Cancer SCC-4 Cells

Shang

Chen

Chou

et al. 2020

In Vivo

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Background/Aim: Casticin, one of the active components of Vitex rotundifolia L., presents biological and pharmacological activities including inhibition of migration, invasion and induction of apoptosis in numerous human cancer cells in vitro. This study aimed to assess the effects of casticin on tumor growth in a human oral cancer SCC-4 cell xenograft mouse model in vivo. Materials and Methods: Twenty-four nude mice were injected subcutaneously with SCC-4 cells and when palpable tumors reached a volume of 100-120 mm 3 the mice were randomly divided into three groups. The control (0.1% dimethyl sulfoxide), casticin (0.2 mg/kg), and casticin (0.4 mg/kg) groups were intraperitoneally injected every two days for 18 days. Tumor volume and body weights were measured every two days. Results: Casticin significantly decreased tumor volume and weight in SCC-4 cell xenograft mice but there was no statistically significant difference between the body weights of control mice and mice treated with 0.2 mg/kg or 0.4 mg/kg casticin. Therefore, the growth of SCC-4 cells in athymic nude mice can be inhibited by casticin in vivo. Conclusion: These findings support further investigations in the potential use of casticin as an oral anticancer drug in the future. Oral cancer has high mortality and morbidity (1) that appears on the lips, cheeks, tongue, gingiva, the floor of the mouth, hard and soft palate, sinuses, and pharynx (2). Oral squamous cell carcinoma (OSCC) is one of the leading cancers worldwide, representing over 90% of malignant neoplasms of the mouth (3, 4). However, OSCC occurs more frequently in individuals with oral bacterial infections such as higher levels of periodontal pathogenic bacteria in OSCC surfaces (5). In the USA, about 11.3 new cases of oral cancer per 100,000 people are diagnosed every year (6). In Canada,

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Section: Discussionsupporting

confidence: 93%

Casticin Inhibits In Vivo Growth of Xenograft Tumors of Human Oral Cancer SCC-4 Cells

Shang

Chen

Chou

et al. 2020

In Vivo

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“…DNMT1 plays an essential role in CSLC feature maintenance and frequently decreased miR-34a expression in CSLCs [10–15, 22–25]. So, we initially compared the DNMT activation as well as miR-34a expression and promoter methylation between OSLCs (the sphere-forming U2OS cells) and U2OS cells (the monolayer U2OS cells).…”

Section: Resultsmentioning

confidence: 99%

“…Aberrant DNA methylation promotes the self-renewable capacity of ovarian CSLCs [16, 19]. DNA methyltransferase 1 (DNMT1) contributed to the maintenance of stemness of various CSLCs [20–25], including OSLCs [10, 11]. According to a study using mammary gland-specific DNMT1-knockout mice, DNMT1 deletion limited the CSLC population and reduced mammary tumorigenesis [20].…”

Section: Introductionmentioning

confidence: 99%

The DNMT1/miR-34a Axis Is Involved in the Stemness of Human Osteosarcoma Cells and Derived Stem-Like Cells

Liang

Wang

et al. 2019

Stem Cells International

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The DNA methyltransferase 1 (DNMT1)/miR-34a axis promoted carcinogenesis of various types of cancers. However, no literature reported its contribution to the stemness of osteosarcoma cancer stem-like cells (OSLCs). We sought to determine whether the DNMT1/miR-34a axis facilitates the stemness of OSLCs. We here revealed the higher DNMT1 activity and expression, lower miR-34a expression with high methylation of its promoter, and stronger stemness of OSLCs, as manifested by elevated sphere and colony formation capacities; CD133, CD44, ABCG2, Bmi1, Sox2, and Oct4 protein amounts in vitro; and carcinogenicity in a nude mouse xenograft model, when compared to the parental U2OS cells. 5-Azacytidine (Aza-dC) repressed DNMT1 activation and upregulated miR-34a expression by promoter demethylation and suppressed the stemness of OSLCs in a dose-dependent manner. DNMT1 knockdown increased miR-34a and reduced the stemness of OSLCs. Transfection with a miR-34a mimic repressed the stemness of OSLCs but did not alter DNMT1 activity and expression. Conversely, DNMT1 overexpression declined miR-34a levels, promoting the stemness of U2OS cells. Transfection with a miR-34a inhibitor enhanced the stemness of U2OS cells, without affecting the DNMT1 activity and expression. Importantly, reexpression of miR-34a could rescue the effects of DNMT1 overexpression on miR-34a inhibition as well as the stemness promotion without affecting the activity and expression of DNMT1. Our results revealed that aberrant activation of DNMT1 caused promoter methylation of miR-34a, leading to miR-34a underexpression, and the role of the DNMT1/miR-34a axis in promoting and sustaining the stemness of OSLCs.

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“…Many studies have been done on cytotoxic activity of VAC extracts and their major compounds [7,[23][24][25]. Several studies have demonstrated that the extracts of VAC showed remarkable cytotoxic activity against various human cancer cell lines [23][24][25]. In this study, besides the extracts, the effect of casticin was also investigated on NRK and HeLa cells.…”

Section: Discussionmentioning

confidence: 99%

Identification, antioxidant and cytotoxic potentials of casticin in Vitex agnus-castus fruit from different geographical regions of Turkey

Toplan¹,

Özkan²,

Taşkın³

et al. 2020

Trop. J. Pharm Res

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Purpose: To evaluate the antioxidant and cytotoxic effects, and casticin contents of Vitex agnus-castus (VAC) fruit extract from five geographical regions of Turkey.Methods: Casticin determination in VAC fruit extracts was performed using HPLC-DAD method. The method was validated for linearity, sensitivity, selectivity, accuracy and precision. The methanol extracts of the VAC fruits were analyzed for antioxidant effects using 2,2-diphenyl-1-picrylhydrazyl (DPPH•) radical scavenging capacity, metal-chelation capacity assay, radical cation scavenging capacity (ABTS•+), and total phenolic content. The cytotoxic potential of the extracts against NRK-52E and HeLa cells were determined using MTT and LDH assays.Results: The casticin content of the extracts ranged from 0.048 and 0.152 %. Total phenol content was in the range of 36.67 ± 0.7 to 74.20 ± 1.02 mg gallic acid equivalent (GAE)/100 mg of extracts. High-tomoderate antioxidant properties were observed in the extracts. Cytotoxicity data demonstrated that all extracts showed high cytotoxic effects on HeLa cell line when compared to the NRK-52E cell line (p < 0.05).Conclusion: These results suggest that VAC fruits (Monk’s pepper fruits) from Aegean sea coasts have a potential for use in the preparation of phytopharmaceutical products. Keywords: Vitex agnus-castus, Casticin, Antioxidant, Cytotoxic activity, Anticancer

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Casticin inhibits the activity of transcription factor Sp1 and the methylation of RECK in MGC803 gastric cancer cells

Cited by 13 publications

References 45 publications

Casticin Inhibits In Vivo Growth of Xenograft Tumors of Human Oral Cancer SCC-4 Cells

Casticin Inhibits In Vivo Growth of Xenograft Tumors of Human Oral Cancer SCC-4 Cells

The DNMT1/miR-34a Axis Is Involved in the Stemness of Human Osteosarcoma Cells and Derived Stem-Like Cells

Identification, antioxidant and cytotoxic potentials of casticin in Vitex agnus-castus fruit from different geographical regions of Turkey

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