Sweet Wormwood and Tortoise Shell Decoction (Thanh Hao Miet Giap Thang) Induces DNA Damage, S-Phase Arrest, and Apoptosis in MCF-7 Cells via ATR-CHK1 Signaling Pathway.

Introduction: Sweet wormwood and tortoise shell decoction, Thanh Hao Miet Giap Thang (THMGT) in Vietnamese, a traditional formula composed of five ingredients, is used in complementary care in Vietnam for patients who underwent conventional cancer treatment. To expand the clinical use and explore novel functions of THMGT, this study was conducted to investigate the effect of THMGT in terms of antiproliferative activity and selective cytotoxicity toward human breast cancer cells MCF-7. Methods: Cytotoxicity of THMGT against human breast cancer cells MCF-7 and primary fibroblasts from a heathy donor were studied using sulforhodamine B (SRB) assay. Flow cytometry analysis, immunofluorescence, and western blotting were also performed to elucidate underlying mechanisms of THMGT action. Results: The SRB assay on treated MCF-7 cells and primary fibroblasts from a heathy donor indicated selective cytotoxicity of THMGT with a selective index of 3.92. Annexin V/PI staining and flow cytometric analysis on stained MCF-7 cells showed that the THMGT-treated cells were arrested at the S phase and subsequently underwent apoptosis. Western blot analysis showed an upregulation of γ-H2AX, increased protein levels of phosphorylated CHK1, TP53, and phosphorylated TP53 in a time-dependent manner, and a downregulated expression of ATR and MDM2. Conclusion: These results suggested DNA damaging effect and ATR-CHK1-mediated cell cycle arrest of THMGT on MCF-7 cells resulting in apoptosis induction.

Presence of Hypertrophic Cardiomyopathy Related Gene Mutations and Clinical Manifestations in Vietnamese Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is associated primarily with pathogenic mutations in sarcomeric genes. The aim of this study was to identify the prevalence and distribution of disease-causing mutations in HCM-associated genes and the genotype-phenotype relationship in Vietnamese patients with HCM.Methods and Results:Genetic testing was performed by next-generation sequencing in 104 unrelated probands for 23 HCM-related genes and in 57 family members for the mutation(s) detected. Clinical manifestations were recorded for genotype-phenotype correlation analysis. Mutation detection rate was 43.4%. Mutations inMYBPC3accounted for 38.6%, followed byTPM1(20.5%),MYH7(18.2%),TNNT2(9.1%),TNNI3(4.5%) andMYL2(2.3%). A mutation inGLAassociated with Fabry disease was found in 1 patient. A mutation inTPM1(c.842T>C, p.Met281Thr) was identified in 8 unrelated probands (18.2%) and 8 family members from 5 probands. Genotype-positive status related toMYH7,TPM1, andTNNT2mutations was associated with severe clinical manifestations.MYH7-positive patients displayed worse prognosis compared withMYBPC3-positive patients. Interestingly,TPM1c.842T>C mutation was associated with high penetrance and severe HCM phenotype. CONCLUSIONS: We report for the first time the prevalence of HCM-related gene variants in Vietnamese patients with HCM.MYH7,TPM1, andTNNT2mutations were associated with unfavorable prognosis.