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Abstract
The critical analysis of preclinical testing of anticarcinogenic and antitumor activity of biguanides presented in this paper. Experiments have been conducted using in total more than 20 models of carcinogenesis including models of spontaneous , chemically- , radiation- and virus-induced carcinogenesis, as well as carcinoigenesis induced by special fat diets and by genetic modification in rodents. Cancer preventive effect of buiguanides has been studied in relation to total tumor incidence and to 17 target organs in animals of 3 species, including 25 various strains of mice, 4 strains of rats and 1 strain of hamsters using various routs of administration and doses. In the majority of cases (86%) the exposure to biguanides leads to inhibition of carcinogenesis. In 14% of the cases inhibitory effect of the drugs was not observed, however there was no any case of stimulation of carcinogenesis by antidiabetic biguanides., Metformin suppressed tumor growth in the majority of in vitro studies conducted in 46 different cell lines originated from malignant tumors of 15 localization as well as in athymic mice with xenografts of 31 tumor lines. It was concluded that there are sufficient experimental evidences of anticarcinogenic and antitumor effects of antidiabetic biguanides revealed in a number of models of induced and spontaneous carcinogenesis.References
Анисимов В.Н. Влияние буформина и дифенина на продолжительность жизни, астральную функцию и частоту спонтанных опухолей у самок крыс // Вопр. онкол. -1980. - Т 26. № 6. - С. 42-28.
Анисимов В.Н., Александров В.А., Белоус Н.М., Васильева И.А. Торможение буформином трансплацентарного бластомогенного аффекта N-нитрозометил-мочевины у крыс // Бюлл. акспер. биол. мед. - 1980. - Т. 89. - № 7. - С. 88-90.
Анисимов В.Н., Белоус Н.М., Васильева И.А., Дильман В.М. Торможение фенформином развития опухолей молочной железы, индуцированных у крыс N-нитрозометилмочевиной // Экспер. онкол. - 1980. - Т. 2. - № 3. - С. 40-43.
Анисимов В.Н., Белоус Н.М., Прокудина Е.А. Торможение фенформином радиационного канцерогенеза у самок крыс // Экспер.онкол.- 1982. - Т. 4ю - № 6. - С. 26-29.
Анисимов В.Н., Пожарисский К.М., Дильман В.М. Влияние фенформина на бластомогенный аффект 1,2-ди-метилгидразина // Вопр. онкол. - 1980. - Т. 26. - № 8. - С. 54-58.
Берштейн Л. М. Бигуаниды: экспансия в практическую онкологию: (прошлое и настоящее) / - Санкт-Петербург: Эскулап, 2010. - 141 с.
Дильман В.М., Софронов В.Н., Анисимов В.Н. и др. Устранение фенформином иммунодепрессии, вызванной 1,2 - диметилгидразином у крыс // Вопр. онкол. - 1977. - Т. 23. - № 8. - С. 50-54.
Пархитько А. А., Фаворова О. О., Анисимов В. Н., Хенске Э. П. Киназа mTOR:регуляция, роль в поддержании клеточного гомеостаза, развитии опухолей и старении // Биохимия. 2014. - Т. 79. - № 2. - С. 128-143.
Шихман А.Р., Лебедев К.А., Дильман М.В. Тормозящее влияние фенформина (фенитилбигуанида) на рост карциномы Эрлиха // Вопр. онкол. - 1981. - № 2. - С. 67-69.
Alexandrov V.A., Anisimov V.N., Belous N.M. et al. The inhibition of the transplacental blastomogenic effect of nitrosomethylurea by postnatal administration of buformin to rats // Carcinogenesis. - 1980. - Vol. 1. - Р 975-978.
Algire C., Zakikhani M., Blouin M.J. et al. Metformin attenuates the stimulatory effect of a high-energy diet on in vivo LLC1 carcinoma growth // Endocr. Relat. Cancer. - 2008. - Vol. 15. - P. 833-839.
Anisimov V.N. Carcinogenesis and Aging, Vols. 2. - Boca Raton, FL: CRC Press, Inc., 1987. - 146 p.
Anisimov V.N. Do metformin a real anticarcinogen? A critical reapraisal of experimental data // Ann. Transl. Med. - 2014. - Vol. 2. - No. 6. - P. 60.
Anisimov V.N. Metfomin for cancer and aging preventiom: is it a time to make the long story short? // Oncotarget. - 2015. - Vol. 6. - № 37. - P. 39398-39407.
Anisimov V.N., Bartke A. The key role of growth hormone - insulin - IGF-1 signaling in aging and cancer // Critical Rev. Oncology/Hematology. 2013. -Vol. 87. - P. 201-223.
Anisimov V.N., Berstein L.M., Egormin P.A. et al. Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice // Exp. Gerontol. 2005. -Vol. 40. - P.685-693.
Anisimov V.N., Berstein L.M., Egormin P.A., et al. Metformin slows down aging and extends life span of female SHR mice // Cell Cycle. - 2008. - Vol. 7. - P.2769-2773.
Anisimov V.N., Berstein L.M., Popovich I.G. et al. If started early in life, metformin increases life span and postpones tumors in female SHR mice. // Aging (Albany, NY). - 2011. - Vol. 3. - P. 148-157.
Anisimov V.N., Egormin P.A., Piskunova T.S. et al. Metformin extends life span of HER-2/neu transgenic mice and in combination with melatonin inhibits growth of transplantable tumors in vivo // Cell Cycle, 2010. - Vol. 9. - P. 188-197.
Anisimov V.N., Piskunova T.S., Popovich I.G. et al. Gender differences in metformin effect on aging, life span and spontaneous tumorigenesis in 129/Sv mice // Aging (Albany, NY). - 2011. -Vol. 2. - P. 945-958.
Anisimov V.N., Popovich I.G., Zabezhinski M.A. et al. Sex differences in aging, life span and spontaneous tumori-genesis in 129/Sv mice neonatally exposed to metformin. // Cell Cycle. - 2015. -Vol. 14. - No. 1. - P. 46-55.
Anisimov V.N., Semenchenko A.V., Yashin A.I. Insulin and longevity: antidiabetic biguanides as geroprotectors // Biogerontology. - 2003. - Vol. 4. - № 5. - P. 297-307.
Bannister C.A., Holden S.E., Jenkins-Jones S. et al. Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls // Diabetes Obes. Metab. - 2014. - Vol. 16. - P. 1165-1173.
Berstein L.V. Metformin in obesity, cancer and aging: addressing controversies. // Aging (Albany NY). - 2012. -Vol. 4. - P. 320-329.
Blagosklonny M.V. Common drugs and treatments for cancer and age-related diseases: revitalizing answers to NCI’s provocative questions // Oncotarget. - 2012.- Vol. 3. - P. 1711-1724.
Blagosklonny M.V. Selective anti-cancer agents as antiaging drugs // Cancer Biol. Ther. - 2013. - Vol. 14. -P.1092-1097.
Bolin L., Zeying F., Susan M. et al. Metformin induces unique biological and molecular responses in triple negative breast cancer cells // Cell Cycle. - 2009. - Vol. 8. - P. 2031-2040.
Bowker S.L., Majumdar S.R., Veugelers P., Johnson J.A. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylurea or insulin. // Diabetes Care. - 2006. - Vol. 29. P. 254-258.
Brodowska K., Theodoropoulou S., Meyer Zu Hörste M. et al. Effects of metformin on retinoblastoma growth in vitro and in vivo // Int. J. Oncol. - 2014. - Vol. 45. - P. 2311-2324.
Chandel N. Four key questions about metformin and cancer // BMC Biol. - 2014. - Vol. 24. - P. 12-85.
Chen X., Hu C., Zhang W. Metformin inhibits the proliferation, metastasis, and cancer stem-like sphere formation in osteosarcoma MG63 cells in vitro // Tumour Biol. - 2015. - Vol. 36 -P. 9873-9883.
Chen Y., Chen G. Combined therapeutic effect and molecular mechanisms of metformin and cisplatin in human lung cancer xenografts in nude mice // J. Cancer Res. Ther. - 2015. - Vol. 11. - P. 324-330.
Cheong J. Dual inhibition of tumor energy pathway by 2-deoxyglucose and metformin. Is effective against a broad spectrum of preclinical cancer models // Mol. Cancer Therap. - 2011. - Vol. 10 (12). - P. 2350-2362.
Cho S., Yi K., Han S. Therapeutic potential of metformin in papillary thyroid cancer in vitro and in vivo // Mol. Cell Endocrinol. - 2014. - Vol. 393. - P. 24-29.
Cohen M.H., Strauss B.L. Enhancement of the antitumor effect of 1,3-bis(2-chloroethyl)-l-nitrosourea (BCNU) by phenylethylbiguanide (phenformin) // Oncology. - 1976. - Vol. 33. - P. 257-259.
Corominas-Faja B., Quirantes-Piné R., Oliveras-Ferraros C. et al. Metabolomic fingerprint reveals that metformin impairs one-carbon metabolism in a manner similar to the antifolate class of chemotherapy drugs // Aging (Albany NY). - 2012. - Vol. 4. - P. 80-98.
Dilman V.M. Age-associated elevation of hypothalamic threshold to feedback control and its role in development, aging and disease // Lancet. 1971. - Vol. 1. - P. 1211-1219.
Dilman V.M. Ageing, metabolic immunodepression and carcinogenesis // Mech. Ageing Dev. - 1978. -Vol. 8. -P. 153-173.
Dilman V.M., Anisimov V.N. Potentiation of anti-tumor effect of cyclophosphamide and hydrazine sulfate by treatment with the antidiabetic agent, 1-phenylethylbuguanide (phenformin) // Cancer Lett. - 1979. - Vol. 7. - P. 357-361.
Dilman V.M., Anisimov V.N., Effect of treatment with phenformin, diphenylhydantoin or L-DOPA on life span and tumor incidence in C3H/Sn mice // Gerontology.- 1980. - Vol. 26. - Р. 241-246.
Dilman V.M., Berstein L.M., Yevtushenko T.P. et al. Preliminary evidence on metabolic rehabilitation in cancer patients // Arch. Geschwulstforsch. - 1988. - Vol. 58. -P. 175-183.
Dilman V.M., Berstein L.M., Zabezhinski M.A. et al. Inhibition of DMBA-induced carcinogenesis by phenformin in the mammary gland of rats // Arch. Geschwulstforsch. - 1978. - Vol. 48. - P. 1-8.
Evans J.M., Donnelly A., Emslie-Smith A.M. et al. Metformin and reduced risk of cancer in diabetic patients. // BMJ. - 2005. - Vol. 330. - P. 1304-1305.
Fujihara S., Kato K., Morishita A. et al. Antidiabetic drug metformin inhibits esophageal adenocarcinoma cell proliferation in vitro and in vivo // Int. J. Oncol. - 2015. - Vol. 46. - P. 2172-2180.
Fujimori T., Kato K., Fujihara S. et al. Antitumor effect of metformin on cholangiocarcinoma: In vitro and in vivo studies // Oncol Rep. - 2015. - Vol. 34. - P. 2987-2996.
Graham G.G., Punt J., Arora M. Clinical pharmacokinetics of metformin // Clin. Pharmacokinet. - 2011. - Vol. 50 (2). - P. 81-98.
Grossmann M.E., Yang D.Q., Guo Z. et al. Metformin treatment for the prevention and /or treatment of breast/ mammary tumorigenesis // Curr. Pharmacol. Rep. - 2015. - Vol. 1. - P. 312-323.
Halicka H.D., Zhao H., Li J. et al. Potential anti-aging agents suppress the level of constitutive mTOR- and DNA damage- signaling // Aging (Albany NY). - 2012. -Vol. 4. - P. 952-965.
Halicka H.D., Zhao H., Li J. et al. Genome protective effect of metformin as revealed by reduced level of constitutive DNA damage signaling // Aging (Albany NY). -2011. - Vol. 3. - P. 1028-1038.
Hall S.S. A trial for the ages // Science. - 2015. - Vol. 349. - P. 1275-1278.
Hirsch H.A., Iliopoulos D., Struhl K. Metformin inhibits the inflammatory response associated with cellular transformation and cancer stem cell growth // Proc. Natl. Acad. Sci. U S A. - 2013. - Vol. 110. - P. 972-977.0
Ilipoulos D., Hirsch H.A., Struhl K. Metformin decreases the doses of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types // Cancer Res. - 2011. - Vol. 71. - P. 3196-3201.
Jia Y, Ma Z., Liu X. et al. Metformin prevents DMH-induced colorectal cancer in diabetic rats by reversing the warburg effect // Cancer Med. - 2015. - Vol. 4 (11). - P. 1730-1741.
Jiang X., Ma N., Wang D. et al. Metformin inhibits tumor growth by regulating multiple miRNAs in human cholangiocarcinoma // Oncotarget. - 2015. - Vol. 6 (5). - P. 3178-94.
Kasznicki J., Sliwinska A., Drzewoski Z.J. Metformin in cancer prevention and therapy // Ann. Transl. Med. -2014. - Vol. 2 (6). - P. 57.
Kowal B., Stang A., Rathmann W., Kostev K. No reduced risk of overall, colorectal, lung, breast, and prostate cancer with metformin therapy in diabetic patients: database analyses from Germany and the UK // Pharmacoepidemiol Drug. Saf. - 2015. Jul 1. doi: 10.1002/ pds.3823.
Kumar A., Al-Sammarraie N., Di Pette D., Singh U. Metformin impairs Rho GTPase signaling to induce apoptosis in neuroblastoma cells and inhibits growth of tumors in the xenograft mouse model of neuroblastoma // Oncotarget. - 2014. - Vol. 5 (22). - P. 11709-11722.
Lau Y., Du X., Rayannavar V. Metformin and erlotinib synergize to inhibit basal breast cancer // Oncotarget. - 2014. - Vol. 5 (21). - P. 10503-10517.
Lengyel E., Litchfield L., Mitra A. et al. Metformin inhibits ovarian cancer growth and increases sensitivity to paclitaxel in mouse models // Am. J. Obstet. Gynecol. - 2015. - Vol. 212 (4). - P.479.e1-479.e10.
Li J., Hernanda P.Y., Bramer W.M. et al. Anti-tumor effects of metformin in animal models of hepatocellular carcinoma: a systematic review and meta-analysis // PLoS One. -2015. Jun 1. - Vol. 10 (6). - e 0127967.
Li W., Wang Q.L., Liu X. et al. Combined use of vitamin D3 and metformin exhibits synergistic chemopreventive effects on colorectal neoplasia in rats and mice // Cancer Prev. Res. (Phila). -2015. - Vol.8. - P. 139-148.
Ling S., Tian Y., Zhang H. Metformin reverses multidrug resistance in human hepatocellular carcinoma Bel-7402/5-fluorouracil cells // Mol. Med. Rep. - 2014. - Vol. 10. - P. 2891-2897.
Lugaro G., Giannattasio G. Effect of biguanides on the respiration of tumour cells // Experientia. - 1968. - Vol. 4. - P. 794-795.
Martin-Castillo B., Vazquez-Martin A, Oliveras-Ferraros C, Menendez JA. Metformin and cancer// Doses, mechanisms and the dandelion and hermetic phenomen // Cell Cycle. - 2010. - Vol. 9. - P. 1057-1064.
Moiseeva O., Deschênes-Simard X., Pollak M., Ferbeyre G. Metformin, aging and cancer. // Aging (Albany NY). - 2013. - Vol. 5. - P. 330-331.
Nangia-Makker P., Yingjie Y., Vasudevan A. Metformin: A Potential Therapeutic Agent for Recurrent Colon Cancer // PLoS One. - 2014. - Vol. 9 (1). - P. e84369.
Phoenix K., Vumbaca F., Claffey K. Therapeutic metformin/AMPK activation promotes the angiogenic phenotype in the ERalpha negative MDA-MB-435 breast cancer model // Breast Cancer Res. Treat. - 2008. - Vol. 113. - P. 101-111.
Pollak M. Potential applications for biguanides in oncology // J. Clin. Invest. - 2013 - Vol. 123. - P. 3693-3700.
Preamble to the IARC Handbooks of Cancer Prevention. IARC Handbooks of Cancer Prevention. Carotenoids. -Vol. 2. - Lyon: IARC. - 1998. - Vol. 2. - P. 3-14.
Quinn B.J., Kitagawa H., Memmott R.M. Repositioning metformin for cancer prevention and treatment // Trends Endocrinol. Metab. - 2013. - Vol. 24. - P. 469-480.
Reagan-Shaw S., Nihal M., Ahmad N. Dose translation from animal to human studies revisited. // FASEB J. -2008. - Vol. 22. - P. 659-661.
Rocha G., Dias M., Ropelle E. et al. Metformin Amplifies Chemotherapy-Induced AMPK Activation and Antitumoral Growth // Clin. Cancer Res. - 2011. - Vol. 17 (12). - P. 3993-4005.
Sadighi S., Amanpour S., Behrouzi B. et al. Lack of metformin effects on different molecular subtypes of breast cancer under normoglycemic conditions: an in vitro study // Asian Pac. J. Cancer Prev. - 2014. - Vol. 15 (5). - P. 2287-2290.
Saito T., Chiba T., Yuki K. Metformin, a diabetes drug, eliminates tumor-initiating Hepatocellular Carcinoma Cells // PLoS One. - 2013. - Vol. 8 (7). -e70010.
Schneider M.B., Matsuzaki H., Haorah J. et al. Prevention of pancreatic cancer induction in hamsters by metformin. // Gastroenterology. - 2010. - Vol. 120.- P. 1263-1270.
Schrauwena S., Coenegrachtsa L., Cattaneoa A. The antitumor effect of metformin with and without carboplatin on primary endometrioid endometrial carcinoma in vivo // Gynecologic Oncology - 2015. - Vol. 138. - P. 378-382.
Sesen J., Dahan P., Scotland S. et al. Metformin inhibits growth of Human glioblastoma Cell. and Enhances Therapeutic Response // PLoS One. - 2015. - Vol. 10 (4). - e 0123721.
Shi W., Xiao D., Wang L. et al. Therapeutic metformin/ AMPK activation blocked lymphoma cell growth via inhibition of mTOR pathway and induction of autophagy // Cell Death Dis. - 2012. - Vol. 3. - e 275.
Suwei D., Liang Z., Zhimin L. et al. NLK functions to main tain proliferation and stemness of NSCLC and is a target of metformin // J. Hematol. Oncol. - 2015. - Vol. 8 (1). - P. 120.
Tan X.L., Bhattacharyya K.K., Dutta S.K. et al. Metformin supresses pancreatic tumor growth with inhibition of NFkB / STAT3 inflammatory signal. // Pancreas - 2015. - Vol. 44. - P. 636-647.
Taubes G. Cancer prevention with a diabetes pill? // Science. - 2012. - Vol.3 35. - P. 29.
Wang L., Wang Z., Zhao X. et al. The inhibitory effect of metformin on oral squamous cell carcinoma // Zhonghua Kou Qiang Yi Xue Za Zhi. - 2015. - Vol. 50. - P. 360-365.
Wang Y., Wei J., Li L. et al. Combined use of metformin and everolimus is yynergistic in the treatment of breast cancer cells // Oncol. Res. - 2015. - Vol. 22 (4). - P. 193-201.
Wu L, Zhu L, Prokop LJ, Murad MH. Pharmacologic therapy of diabetes and overall cancer risk and morality: a meta-analysis of 265 studies // Sci. Rep. - 2015. -5,10147; doi: 10.1038/srep10147.
Xianbin C., Xi H., Xiaojun T. et al. Metformin Induced AMPK Activation, G0/G1 Phase Cell Cycle Arrest and the Inhibition of Growth of Esophageal Squamous Cell Carcinomas In Vitro and In Vivo // PLoS One. - 2015. - Vol. 10 (7). - e0133349.
Yan W., Lin F., Wen T. et al. Metformin induces apoptosis in hepatocellular carcinoma Huh-7 cells in vitro and its mechanism // Zhonghua Zhong Liu Za Zhi. - 2013. - Vol. 35 (10). - P 742-746.
Yasmeen A., Beauchamp MC, Piura E. Induction of apoptosis by metformin in epithelial ovarian cancer: involvement of the Bcl-2 family proteins // Gynecol Oncol. -2011. - Vol. 121. - P 492-498.
Zhang T., Guo P., Zhang Y. et al. The antidiabetic drug metformin inhibits the proliferation of bladder cancer cells in vitro and in vivo // Int. J. Mol. Sci. - 2013. - Vol. 14. - P. 4603-24618.
Zhiyun Y., Gang Z., Guifang X. et al. Metformin and temozolomide act synergistically to inhibit growth of glioma cells and glioma stem cells in vitro and in vivo // Oncotarget. - 2015. - Vol. 6 (32). - P. 32930-32943.
Zhuang Y., Miskimins W. Cell cycle arrest in Metformin treated breast cancer cells involves activation of AMPK, downregulation of cyclin D1, and requires p27Kip1 or p21Cip1 // J. Mol. Signal. - 2008. - Vol. 3. - P. 18.
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