سامانه مدیریت نشریات علمی دانشگاه علوم پزشکی مشهد

Jafari-Gharabaghlou, Davoud, Pilehvar-Soltanahmadi, Younes, Dadashpour, Mehdi, Mota, Ali, Vafajouy-Jamshidi, Soheila, Faramarzi, Leila, Rasouli, Sara, Zarghami, Nosratollah. (1397). Combination of metformin and phenformin synergistically inhibits proliferation and hTERT expression in human breast cancer cells. , 21(11), 1167-1173. doi: 10.22038/ijbms.2018.30460.7345
Davoud Jafari-Gharabaghlou; Younes Pilehvar-Soltanahmadi; Mehdi Dadashpour; Ali Mota; Soheila Vafajouy-Jamshidi; Leila Faramarzi; Sara Rasouli; Nosratollah Zarghami. "Combination of metformin and phenformin synergistically inhibits proliferation and hTERT expression in human breast cancer cells". , 21, 11, 1397, 1167-1173. doi: 10.22038/ijbms.2018.30460.7345
Jafari-Gharabaghlou, Davoud, Pilehvar-Soltanahmadi, Younes, Dadashpour, Mehdi, Mota, Ali, Vafajouy-Jamshidi, Soheila, Faramarzi, Leila, Rasouli, Sara, Zarghami, Nosratollah. (1397). 'Combination of metformin and phenformin synergistically inhibits proliferation and hTERT expression in human breast cancer cells', , 21(11), pp. 1167-1173. doi: 10.22038/ijbms.2018.30460.7345
Jafari-Gharabaghlou, Davoud, Pilehvar-Soltanahmadi, Younes, Dadashpour, Mehdi, Mota, Ali, Vafajouy-Jamshidi, Soheila, Faramarzi, Leila, Rasouli, Sara, Zarghami, Nosratollah. Combination of metformin and phenformin synergistically inhibits proliferation and hTERT expression in human breast cancer cells. , 1397; 21(11): 1167-1173. doi: 10.22038/ijbms.2018.30460.7345

Combination of metformin and phenformin synergistically inhibits proliferation and hTERT expression in human breast cancer cells

Iranian Journal of Basic Medical Sciences
مقاله 11، دوره 21، شماره 11، بهمن 2018، صفحه 1167-1173    اصل مقاله (634.18 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2018.30460.7345
نویسندگان
Davoud Jafari-Gharabaghlou1، 2؛ Younes Pilehvar-Soltanahmadi3، 2، 4؛ Mehdi Dadashpour3، 4؛ Ali Mota1؛ Soheila Vafajouy-Jamshidi1؛ Leila Faramarzi1؛ Sara Rasouli1؛ Nosratollah Zarghami* 1، 3، 2، 4
1Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
3Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
4Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
چکیده
Objective(s): Breast cancer remains a global challenge, and further chemopreventive therapies are still immediately required. Emerging evidence has revealed the potent anti-cancer effects of biguanides, Metformin (MET) and phenformin (PHE). Thus, to explore an efficient chemopreventive strategy for breast cancer, the antiproliferative effects of the combination of MET and PHE against breast cancer cells were assessed.
Materials and Methods: Cytotoxicity of the drugs individually and in combination against T47D and MDA-MB-231 breast cancer cells were assessed using MTT assay and the median-effect method was used to analyze the precise nature of the interaction between MET and PHE. Besides, the expression levels of hTERT after 48 hr drug exposure were determined using qRT-PCR.
Results: Based on the cytotoxicity assay, both MET and PHE further inhibited the growth of MDA-MB-231 cells compared with T47D cells. It was found that MET+PHE reduced the IC50s of MET and PHE in both cells drastically more than the single treatments in a synergistic manner. Importantly, MET+PHE showed higher antiproliferative effect with smaller IC50 values against MDA-MB-231 cells than against T47D cells.
Real-time PCR results revealed that hTERT expression was significantly reduced in both breast cancer cell lines treated with MET+PHE than the single treatments. In comparison between two types of breast cancer cells, it was detected that MET+PHE could further decline hTERT expression in MDA-MB-231cells than in T47D cells (P<0.001).
Conclusion: It is speculated that the combination of MET and PHE may be a promising and convenient approach to improve the efficiency of breast cancer treatment.speculated that the combination of MET and PHE may be a promising and convenient approach to improve the efficiency of breast cancer treatment.
It is speculated that the combination of MET and PHE may be a promising and convenient approach to improve the efficiency of breast cancer treatment.
 
کلیدواژه‌ها
Breast Cancer؛ Combination therapy؛ Metformin؛ Phenformin؛ Synergistic effects
مراجع
1. Smith RA, Andrews KS, Brooks D, Fedewa SA, Manassaram‐Baptiste D, Saslow D, et al. Cancer screening in the United States, 2017: a review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J Clin 2017; 67:100-121.
2. Rami A, Zarghami N. Comparison of inhibitory effect of curcumin nanoparticles and free curcumin in human telomerase reverse transcriptase gene expression in breast cancer. Adv Pharm Bull 2013; 3:127.
3. Saslow D, Boetes C, Burke W, Harms S, Leach MO, Lehman CD, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin 2007; 57:75-89.
4. Anari E, Akbarzadeh A, Zarghami N. Chrysin-loaded PLGA-PEG nanoparticles designed for enhanced effect on the breast cancer cell line. Artif Cells Nanomed Biotechnol 2016; 44:1410-1416.
5. Orecchioni S, Reggiani F, Talarico G, Mancuso P, Calleri A, Gregato G, et al. The biguanides metformin and phenformin inhibit angiogenesis, local and metastatic growth of breast cancer by targeting both neoplastic and microenvironment cells. Int J Cancer 2015; 136:E534-E544.
6. Farajzadeh R, Pilehvar-Soltanahmadi Y, Dadashpour M, Javidfar S, Lotfi-Attari J, Sadeghzadeh H, et al. Nano-encapsulated metformin-curcumin in PLGA/PEG inhibits synergistically growth and hTERT gene expression in human breast cancer cells. Artif Cells Nanomed Biotechnol 2018:46:917-925.
7. Maasomi ZJ, Soltanahmadi YP, Dadashpour M, Alipour S, Abolhasani S, Zarghami N. Synergistic anticancer effects of silibinin and chrysin in T47D breast cancer cells. Asian Pac J Cancer Prev 2017; 18:1283.
8. Mokhtari RB, Homayouni TS, Baluch N, Morgatskaya E, Kumar S, Das B, et al. Combination therapy in combating cancer. Oncotarget 2017; 8: 38022-38043.
9. Lotfi-Attari J, Pilehvar-Soltanahmadi Y, Dadashpour M, Alipour S, Farajzadeh R, Javidfar S, et al. Co-delivery of curcumin and chrysin by polymeric nanoparticles inhibit synergistically growth and hTERT gene expression in human colorectal cancer cells. Nutr Cancer 2017; 69:1290-1299.
10. Javidfar S, Pilehvar-Soltanahmadi Y, Farajzadeh R, Lotfi-Attari J, Shafiei-Irannejad V, Hashemi M, et al. The inhibitory effects of nano-encapsulated metformin on growth and hTERT expression in breast cancer cells. J Drug Deliv Sci Technol 2018; 43: 19-26.
11. Zhang H-H, Guo X-L. Combinational strategies of metformin and chemotherapy in cancers. Cancer Chemother Pharmacol 2016; 78:13-26.
12. Liu Z, Ren L, Liu C, Xia T, Zha X, Wang S. Phenformin induces cell cycle change, apoptosis, and mesenchymal-epithelial transition and regulates the AMPK/mTOR/p70s6k and MAPK/ERK pathways in breast cancer cells. PloS one 2015; 10:e0131207.
13. Alibakhshi A, Ranjbari J, Pilehvar-Soltanahmadi Y, Nasiri M, Mollazade M, Zarghami N. An update on phytochemicals in molecular target therapy of cancer: potential inhibitory effect on telomerase activity. Curr Med Chem Anticancer Agents 2016; 23:2380-2393.
14. Amirsaadat S, Pilehvar-Soltanahmadi Y, Zarghami F, Alipour S, Ebrahimnezhad Z, Zarghami N. Silibinin-loaded magnetic nanoparticles inhibit hTERT gene expression and proliferation of lung cancer cells. Artif Cells Nanomed Biotechnol 2017; 45:1649-1656.
15. Pirmoradi S, Fathi E, Farahzadi R, Pilehvar-Soltanahmadi Y, Zarghami N. Curcumin affects adipose tissue-derived mesenchymal stem cell aging through TERT gene expression. Drug Res (Stuttg) 2018; 68:213-221.
16. Sadeghzadeh H, Pilehvar-Soltanahmadi Y, Akbarzadeh A, Dariushnejad H, Sanjarian F, Zarghami N. The effects of nanoencapsulated curcumin-Fe3O4 on proliferation and hTERT gene expression in lung cancer cells. Anticancer Agents Med Chem 2017; 17:1363-1373.
17. Wang L, Soria J-C, Kemp BL, Liu DD, Mao L, Khuri FR. hTERT expression is a prognostic factor of survival in patients with stage I non-small cell lung cancer. Clin Cancer Res 2002; 8:2883-2889.
18. Tavakoli F, Jahanban-Esfahlan R, Seidi K, Jabbari M, Behzadi R, Pilehvar-Soltanahmadi Y, et al. Effects of nano-encapsulated curcumin-chrysin on telomerase, MMPs and TIMPs gene expression in mouse B16F10 melanoma tumour model. Artif Cells Nanomed Biotechnol 2018:1-12.
19. Rasouli S, Zarghami N. Synergistic Growth Inhibitory Effects of Chrysin and Metformin Combination on Breast Cancer Cells through hTERT and Cyclin D1 Suppression. Asian Pac J Cancer Prev 2018; 19:977-982.
20. Alimova IN, Liu B, Fan Z, Edgerton SM, Dillon T, Lind SE, et al. Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro. Cell cycle 2009; 8:909-915.
21. Dowling RJ, Zakikhani M, Fantus IG, Pollak M, Sonenberg N. Metformin inhibits mammalian target of rapamycin–dependent translation initiation in breast cancer cells. Cancer Res 2007; 67:10804-10812.
22. Zakikhani M, Dowling R, Fantus IG, Sonenberg N, Pollak M. Metformin is an AMP kinase–dependent growth inhibitor for breast cancer cells. Cancer Res 2006; 66:10269-10273.
23. McGuinness ME, Talbert RL. Phenformin-induced lactic acidosis: a forgotten adverse drug reaction. Ann Pharmacother 1993; 27:1183-1187.
24. Zhou J, Huang W, Tao R, Ibaragi S, Lan F, Ido Y, et al. Inactivation of AMPK alters gene expression and promotes growth of prostate cancer cells. Oncogene 2009; 28:1993.
25. Storozhuk Y, Hopmans S, Sanli T, Barron C, Tsiani E, Cutz J, et al. Metformin inhibits growth and enhances radiation response of non-small cell lung cancer (NSCLC) through ATM and AMPK. B Br J Cancer 2013; 108:2021-2032.
26. Li B, Takeda T, Tsuiji K, Kondo A, Kitamura M, Wong TF, et al. The antidiabetic drug metformin inhibits uterine leiomyoma cell proliferation via an AMP-activated protein kinase signaling pathway. Gynecol Endocrinol 2013; 29:87-90.
27. Zordoky BN, Bark D, Soltys CL, Sung MM, Dyck JR. The anti-proliferative effect of metformin in triple-negative MDA-MB-231 breast cancer cells is highly dependent on glucose concentration: implications for cancer therapy and prevention. Biochim Biophys Acta 2014; 1840:1943-1957.
28. Iliopoulos D, Hirsch HA, Struhl K. Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types. Cancer Res 2011; 71:3196-3201.
29. Liu H, Scholz C, Zang C, Schefe JH, Habbel P, Regierer A-C, et al. Metformin and the mTOR inhibitor everolimus (RAD001) sensitize breast cancer cells to the cytotoxic effect of chemotherapeutic drugs in vitro. Anticancer Res 2012; 32:1627-1637.
30. Soo JS-S, Ng C-H, Tan SH, Malik RA, Teh Y-C, Tan B-S, et al. Metformin synergizes 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) combination therapy through impairing intracellular ATP production and DNA repair in breast cancer stem cells. Apoptosis 2015; 20:1373-1387.
31. Vazquez-Martin A, Oliveras-Ferraros C, Del Barco S, Martin-Castillo B, Menendez JA. The anti-diabetic drug metformin suppresses self-renewal and proliferation of trastuzumab-resistant tumor-initiating breast cancer stem cells. Breast Cancer Res Treat 2011; 126:355-364.
32. Cufí S, Corominas-Faja B, Vazquez-Martin A, Oliveras-Ferraros C, Dorca J, Bosch-Barrera J, et al. Metformin-induced preferential killing of breast cancer initiating CD44+ CD24−/low cells is sufficient to overcome primary resistance to trastuzumab in HER2+ human breast cancer xenografts. Oncotarget 2012; 3:395-398.
33. Ma J, Guo Y, Chen S, Zhong C, Xue Y, Zhang Y, et al. Metformin enhances tamoxifen-mediated tumor growth inhibition in ER-positive breast carcinoma. BMC cancer 2014; 14:172-183.
34. Jang SY, Kim A, Kim JK, Kim C, Cho Y-H, Kim J-H, et al. Metformin inhibits tumor cell migration via down-regulation of MMP9 in tamoxifen-resistant breast cancer cells. Anticancer Res 2014; 34:4127-4134.
35. Rocha GZ, Dias MM, Ropelle ER, Osório-Costa F, Rossato FA, Vercesi AE, et al. Metformin amplifies chemotherapy-induced AMPK activation and antitumoral growth. Clin Cancer Res 2011; 17:3993-4005.
36. Miskimins WK, Ahn HJ, Kim JY, Ryu S, Jung Y-S, Choi JY. Synergistic anti-cancer effect of phenformin and oxamate. PloS one 2014; 9:e85576.
37. Peng M, Darko KO, Tao T, Huang Y, Su Q, He C, et al. Combination of metformin with chemotherapeutic drugs via different molecular mechanisms. Cancer Treat Rev 2017; 54:24-33.
38. Uehara T, Mitsuhashi A, Tsuruoka N, Shozu M. Metformin potentiates the anticancer effects of cisplatin under normoxic conditions in vitro. Oncol Rep 2015; 33:744-750.
39. Cantrell LA, Zhou C, Mendivil A, Malloy KM, Gehrig PA, Bae-Jump VL. Metformin is a potent inhibitor of endometrial cancer cell proliferation—implications for a novel treatment strategy. Gynecol Oncol 2010; 116:92-98.
40. Montazeri M, Pilehvar-Soltanahmadi Y, Mohaghegh M, Panahi A, Khodi S, Zarghami N, et al. Antiproliferative and apoptotic effect of dendrosomal curcumin nanoformulation in P53 mutant and wide-type cancer cell lines. Anticancer Agents Med Chem 2017; 17:662-673.
41. Mohammadian F, Pilehvar-Soltanahmadi Y, Zarghami F, Akbarzadeh A, Zarghami N. Upregulation of miR-9 and Let-7a by nanoencapsulated chrysin in gastric cancer cells. Artif Cells Nanomed Biotechnol 2017; 45:1201-1206.
42. Pilehvar-Soltanahmadi Y, Nouri M, Martino MM, Fattahi A, Alizadeh E, Darabi M, Rahmati-Yamchi M, Zarghami N. Cytoprotection, proliferation and epidermal differentiation of adipose tissue-derived stem cells on emu oil based electrospun nanofibrous mat. Exp Cell Res 2017; 357:192-201.

آمار
تعداد مشاهده مقاله: 1,287
تعداد دریافت فایل اصل مقاله: 794