The Cytotoxic Effect of Metformin on RD Cell Line.

Abstract

Background: Cancer is a pathogenesis that happens when modification in collections of normally occurring cells inside the human body occurs leading to non-controlled growth causing a lump called the tumor; this applies to all types of cancers except leukemia (cancer of
 the blood). Doxorubicin (DOX) is one of the highly effective anti-neoplastic drugs of the anthracycline's family used to treat many pediatric and adult cancers, e.g. solid tumors, lymphomas, leukemia and breast cancer. Doxorubicin is known to produce severe cytotoxicity. Metformin (Met) is a biguanide used for type 2 diabetes mellitus. Metformin have cytoprotective effect in addition to reducing basal and postprandial levels of glucose by decreasing the production of ROS, maintaining energy homeostasis and apoptosis regulation by its activation of adenosine monophosphate-activated protein kinase (AMPK). Met has also the ability to increase apoptotic factors and suppression of proliferation thus MET consider as cytotoxic and anti-proliferative drug.
 Objectives: This study was designed to investigate the cytotoxic and antiproliferative effect of Met comparing to DOX as a control in RD cell, also combination of both.
 Materials and Methods: Cell lines that used (Epithelial cells as a normal cell line and RD cell line was taken from human breast cancer) cultured in suitable media potentiated with different concentrations of heat-inactivated human serum. MTT assay (3-(4,5-Dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide) using for detection of cytotoxicity in Epithelial and RD cell lines for duration 72hrs.
 Results: The results showed that treatment with DOX, MET and combination DOX with MET there is significant (p≤ 0.5) cytotoxic, apoptotic and antiproliferative effect and there is potentiation effect between MET and DOX on tumor cells when treated by combination DOX with MET also Met showed a valuable cytotoxic effect through the detection of IC50.
 Conclusion: From the results, it can be concluded that Metformin have a good cytotoxic and antiproliferative effect on tumor cell lines.

Synergistic anticancer effects of doxorubicin and metformin combination therapy: A systematic review

“… 26 (Paiva-Oliveira DI et al2018) [48] . Osteosarcoma Spheres of MNNG/HOS and MG-63 osteosarcoma cell lines Cytotoxicity, cell viability DOX (0.25 Um), Met (5 mM), 48 h Activation of AMPKα signaling pathway 27 (Mohammd AW et al2019) [49] . Breast cancer MCF-7 cell lines Cytotoxicity, proliferation arrest, apoptosis DOX5 uM and Met 10 mM 72 h Met-exhibits a cytoprotective effect, reducing both basal and postprandial glucose levels through the attenuation of ROS production.…”

“…Correspondingly, Kabel et al ( Table 2 ) reported that metformin reduces SphK1 activity and shifts the sphingolipid rheostat towards reduced S1P production [36] . Additionally, a study reported that metformin can exert a cytoprotective effect by decreasing the production of ROS [49] . Doxorubicin can initiate ROS production by binding to cardiolipin and triggering electron leakage by disrupting its function; ROS itself can prompt cell cycle arrest and cell death [9] .…”

Molecular docking , Synthesis and ADME Studies of New Pyrazoline Derivatives as Potential Anticancer Agents.

“…The methodology used to investigate the anticancer activity of (P1-P6) on viability of Lung Cancer Cell Line (A549) by MTT assay (25) was carried out at the College of Pharmacy/ Mustansiriyah University, Iraq. _____________________________________________________________________________________________________________ ________________________________________________ Egypt.…”