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ABSTRACT: This study aimed to investigate the effects of celecoxib, synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylicacid
(CD437) and the combination of the two on cell proliferation, apoptosis, and cycle arrest of human malignant melanoma A375
cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay (MTT assay) was applied to determine the anti-proliferative
effects of the drugs on human malignant melanoma A375 cells. Flow cytometry was performed to investigate the influence of
the drugs on cell cycle and cell apoptosis. Both celecoxib and CD437 could inhibit the growth of human malignant melanoma
A375 cells in a dose-dependent manner. Celecoxib at 80 μmol/L inhibited proliferation, induced apoptosis and G2/M cell cycle arrest of human malignant melanoma A375 cells after treatment for 24 h [proliferation inhibiting rate: (50.2
± 2.51)%, apoptosis rate: (35.91 ± 1.80)%]. CD437 at 10 μmol/L inhibited proliferation, induced apoptosis and G0/G1 cell cycle arrest of human malignant melanoma A375 cells after treatment for 24 h [proliferation inhibiting rate: (58.6 ±
2.38)%, apoptosis rate: (28.03 ± 0.77)%]. Celecoxib in combination with CD437 could significantly enhance the effects of inhibiting
proliferation and inducing apoptosis of human malignant melanoma A375 cells 24 h after treatment compared with the drug alone
[proliferation inhibiting rate: (68.92 ± 1.72)%, apoptosis rate: (42.09 ± 1.05)%, both P<0.05] and decrease the proportion of the S phase in the cell cycle. Celecoxib could inhibit the growth of human malignant
melanoma A375 cells by inducing apoptosis and G2/M cycle arrest. CD437 could inhibit the growth of human malignant melanoma A375 cells by inducing apoptosis and G0/G1 cycle arrest. Celecoxib exhibited additive effects with CD437 on retarding the growth and inducing apoptosis of human malignant
melanoma A375 cells. Celecoxib in combination with CD437 may become an effective method for prevention and treatment of human
melanoma.
Frontiers of Medicine in China 04/2012; 3(1):108-112.
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ABSTRACT: Human malignant melanoma is notoriously resistant to currently available pharmacological modulation. Our aim was to evaluate the anti-tumor effect of a novel synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carbo-xylic acid (CD437) on melanoma cell line A375. Analysis of cell morphology showed that CD437 promoted marked apoptosis in A375 cells. To explore the mechanisms of CD437-induced apoptosis, an NF-kappaB-luciferase reporter assay was performed, demonstrating that apoptosis induction by CD437 required activation of transcription factor NF-kappaB. Importantly, based on the findings that RIG-I (retinoic acid inducible gene I) can be induced by retinotic acid and can activate NF-kappaB through a CARD-containing adaptor protein VISA, we proposed a hypothesis that RIG-I was involved in the signal pathway of NF-kappaB activation induced by CD437 through the adaptor protein VISA. By specially cleaving VISA with hepatitis C virus (HCV) non-structural (NS)3/4A, the RIG-I pathway was blocked, with subsequent simultaneous inhibition of CD437-induced NF-kappaB activation and cell apoptosis in A375 cells. These results support our hypothesis and suggest that RIG-I may be a useful intermediate biologic marker for retinoid chemoprevention and treatment studies.
Archives for Dermatological Research 11/2008; 301(1):15-20. · 2.28 Impact Factor
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ABSTRACT: To investigate the effect of a novel retinoid CD437 and all-trans retinoic acid (ATRA) in inducing cell apoptosis and inhibiting the proliferation of human epidermoid carcinoma A431 cells and normal human epidermal keratinocytes.
MTT assay was used to determine the inhibitory effects of CD437 and ATRA on the growth of A431 cells and normal human epidermal keratinocytes, and the cell morphological changes were observed microscopically. Flow cytometry was used to investigate the effect of CD437 and ATRA on the cell cycle and apoptosis.
CD437 was more effective than ATRA in inhibiting the proliferation of A431 cells and normal human epidermal keratinocytes. CD437 increased the percentage of sub-G1 populations in A431 cells and induced G1 arrest in normal human epidermal keratinocytes. ATRA appeared to be relatively ineffective for inducing apoptosis in A431 cells as compared to CD437. CD437 did not duce obvious apoptosis in normal human epidermal keratinocytes.
CD437 is more effective than ATRA in inhibiting the proliferation and inducing apoptosis in A431 cells and shows selective apoptosis-inducing effect against malignant keratinocytes, suggesting its potential in the prevention or treatment of cutaneous carcinoma.
Nan fang yi ke da xue xue bao = Journal of Southern Medical University 04/2008; 28(3):305-8.
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ABSTRACT: To investigate the mutations of ATP2C1 gene in Chinese patients with Hailey-Hailey disease (HHD).
Genomic DNA was extracted from peripheral blood leukocytes. PCR and direct DNA sequencing were used to detect the mutations in all 27 exons of ATP2C1 gene in patients of two Chinese families and a sporadic patient with HHD.
Three mutations in ATP2C1 gene were found, including 1 nonsense mutation, 1 deletion/frameshift mutation and 1 missense mutation. All of them were novel mutations.
All the three mutations could affect the transcription and translation, and further the function of protein encoded by ATP2C1 gene.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 03/2008; 25(1):63-5.
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Journal of Dermatological Science 09/2006; 43(2):143-5. · 3.72 Impact Factor
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ABSTRACT: To investigate the involvement of E-cadherin-catenin adhesion system in Bowen's disease (BD) and cutaneous squamous cell carcinoma (SCC).
Fifteen normal skin, 28 BD and 18 SCC specimens were stained with monoclonal antibodies against E-cadherin and beta-catenin. Evaluation of the staining results was performed with semi-quantification of the pattern and intensity of staining, percentage of positive cells, and cytoplasmic staining.
Normal skins strongly expressed membranous E-cadherin and beta-catenin, but their expression was remarkably reduced in BD and SCC. Abnormal staining of beta-catenin was observed in the cytoplasm or cell nuclei of BD and SCC.
Abnormal expression of the E-cadherin/catenin complex is common in SCC and BD.
Nan fang yi ke da xue xue bao = Journal of Southern Medical University 09/2006; 26(8):1245-7.
