TY - JOUR ID - 88248 TI - Metformin Modulates Cyclin D1 and P53 Expression to Inhibit Cell Proliferation and to Induce Apoptosis in Cervical Cancer Cell Lines JO - Asian Pacific Journal of Cancer Prevention JA - APJCP LA - en SN - 1513-7368 AU - Yudhani, Ratih Dewi AU - Astuti, Indwiani AU - Mustofa, Mustofa AU - Indarto, Dono AU - Muthmainah, Muthmainah AD - Departement of Pharmacology, Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia. AD - Departement of Pharmacology, Faculty of Medicine, Gadjah Mada University, Yogyakarta, Indonesia. AD - Departement of Phisiology, Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia. AD - Departement of Anatomy, Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia. Y1 - 2019 PY - 2019 VL - 20 IS - 6 SP - 1667 EP - 1673 KW - Metformin KW - HeLa cell KW - Cyclin D1 KW - p53 KW - Apoptosis DO - 10.31557/APJCP.2019.20.6.1667 N2 - Background: Cervical cancer is one of the most prevalent gynecological cancers worldwide and contributes in highmortality of Indonesian women. The efficacy of chemotherapy as a standart therapy for cervical cancer decreases becauseit frequenly rises adverse effects. Recent studies have found that metformin has a potential anticancer effect mostlythrough reduction of cyclin expression and activation of Activated Adenosine Monophosphate Kinase (AMPK). Thisstudy aimed to investigate the effect of metfomin on expression of cyclin D1 and p53 and apoptosis in HeLa cancer cellline. Methods: HeLa cells were treated with various doses of metformin and doxorubicin as a positive control. Cytotoxiceffect of metformin was determined using the MTT assay. Immunocytochemistry was used to assess cyclin D1 and p53expression and apoptosis levels of treated HeLa cells were analyzed using flowcytometry. Data of cyclin D1 expressionwas statistically analyzed using the Kruskal-Wallis test followed by the Tamhane test, whilst ANOVA and Tukey postHoc tests were used to analyze data of p53 and apoptosis level. The significant value was p< 0.05. Results: Metforminwas able to inhibit proliferation of HeLa cells with IC50 60 mM. HeLa cells treated with 60 and 120 mM metforminhad lower cyclin D1 expression than HeLa cells treated without metformin and reached a significant difference (p=0.001). Moreover, 30 mM or higher doses of metformin increase significantly p53 expression (p< 0.001). Induction ofapoptosis was observed in HeLa cells treated with all doses of metformin and reached statistically difference (p= 0.04and p < 0.001). Conclusion: Metformin can modulate cyclin D1 and p53 expression in HeLa cancer cell line, leadingto inhibition of cell proliferation and induction of apoptosis. Other cyclin family members, CDK inhibitors and AMPKsignaling should be further investigated in order to know mechanism of metformin action. UR - https://journal.waocp.org/article_88248.html L1 - https://journal.waocp.org/article_88248_82720f9e76a77c2f600a0c134d80044c.pdf ER -