Hemat Aghagolzadeh Haji ۱ - ۱. School of medicine, Shahroud university of Medical Sciences, Shahroud, Iran.
Hamed Sheibak ۲ - ۲. School of Medicine, Golestan University of Medical Science, Gorgan, Iran.
Mohsen Khosravi ۳ - ۳. School of Medicine, Iran University of Medical Science, Tehran, Iran.
Jahanbakhsh Asadi ۴* - ۴. Department of Biochemistry and Biophysics, Metabolic Disorders Research Center, School of Medicine, Golestan University of Medical Science, Gorgan, Iran.

Background: Metformin is used to lower blood sugar in patients with type II diabetes. Recent research showed that metformin has effects on cancer cell growth. Studies show that metformin can induce apoptosis in certain cancer cell lines. In this study, we examined the effect of metformin on apoptosis in the T۴۷D breast cancer cell line.Methods: The T۴۷D breast cancer cell line was selected and purchased from the Pasteur Institute (Tehran, Iran). Cells were treated with doses of ۵, ۱۰, and ۵۰ μM of metformin at ۲۴, ۴۸, and ۷۲ hours. The transcription levels of genes involved in apoptosis, including caspase-۳, -۸, -۹, and PARP-۱, were evaluated by real-time PCR.Results: The results of this study showed that at all three doses (۵, ۱۰, and ۵۰ μM) of metformin and at three times (۲۴, ۴۸, and ۷۲ h), the expression of caspase-۸ and caspase-۹ were increased. Also, at all doses metformin increased the expression of PARP-۱ at ۴۸ and ۷۲ hours, but at ۲۴ hours the expression of PARP-۱ was not affected.Conclusions: These results indicate that metformin does not affect expression of caspase-۳ at any dose or time point. This study showed that metformin, by increasing the transcription of caspase-۸ and caspase-۹, causes cell death through apoptosis.Background: Metformin is used to lower blood sugar in patients with type II diabetes. Recent research showed that metformin has effects on cancer cell growth. Studies show that metformin can induce apoptosis in certain cancer cell lines. In this study, we examined the effect of metformin on apoptosis in the T۴۷D breast cancer cell line. Methods: The T۴۷D breast cancer cell line was selected and purchased from the Pasteur Institute (Tehran, Iran). Cells were treated with doses of ۵, ۱۰, and ۵۰ μM of metformin at ۲۴, ۴۸, and ۷۲ hours. The transcription levels of genes involved in apoptosis, including caspase-۳, -۸, -۹, and PARP-۱, were evaluated by real-time PCR. Results: The results of this study showed that at all three doses (۵, ۱۰, and ۵۰ μM) of metformin and at three times (۲۴, ۴۸, and ۷۲ h), the expression of caspase-۸ and caspase-۹ were increased. Also, at all doses metformin increased the expression of PARP-۱ at ۴۸ and ۷۲ hours, but at ۲۴ hours the expression of PARP-۱ was not affected. Conclusions: These results indicate that metformin does not affect expression of caspase-۳ at any dose or time point. This study showed that metformin, by increasing the transcription of caspase-۸ and caspase-۹, causes cell death through apoptosis.

Breast cancer, Metformin, Apoptosis.