Radiosensitizing effects of 2-deoxy-D-glucose and ferulic acid on mouse Ehrlich’s Ascites Carcinoma in Swiss albino mice
Keywords:
Ehrlich ascites carcinoma, radiosensitization, apoptosis, 2-deoxy-D-glucose, ferulic acid
Abstract
The objective of the present study is to evaluate the radiosensitizing activity of combination of 2-deoxy-D-glucose (2DG) and ferulic acid (FA) against Ehrlich’s Ascites Carcinoma (EAC) in Swiss albino mice. Extensive DNA damage has been observed in the cells collected from the peritoneal cavity of combined treatment group (2DG+FA+IR) than the other treatment modalities. Treatment of EAC tumor bearing mice with 2DG and FA before 8 Gy of hemi-body γ-radiation has resulted in the significant decrease of tumor volume and tumor weight compared with EAC control group. Further, combination of 2DG and FA along with radiation decreased the viability of tumor cells in the peritoneal fluid of EAC bearing mice. It has been also found that the percentage of EAC apoptotic cells in the peritoneal fluid has been significantly increased in the combined treatment group (2DG+FA+IR) compared with other treatment groups. Combined treatment of 2DG and FA activated caspase-3 and 9, when compared with the treatment given with radiation alone indicated radiosensitizing effect of this combination (2DG+FA). This has been further evidenced by the massive decrease of LDH activity in the 2DG+FA+IR group. On other hand, 2DG and FA combination protects the hematological changes occurred during radiation treatment. Histopathological examinations showed that the combination of 2DG and FA offers protection to normal tissues during radiation treatment. Taken together, the results of the study clearly suggested 2DG and FA combination sensitizes EAC bearing mice to radiation effects at the same time offers protection to normal tissues from radiation-induced damage.
References
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Zheng LF, Dai F, Zhou B, Yang L, Liu ZL. 2008. Prooxidant activity of hydroxycinnamic acids on DNA damage in the presence of Cu (II) ions: mechanism and structure-activity relationship. Food Chem Toxicol., 46:149-156.
Bhattacharya S, Prasanna A, Majumdar P, Kumar RB, Haldar PK. 2011. Antitumor efficacy and amelioration of oxidative stress by Trichosanthes dioica root against Ehrlich ascites carcinoma in mice. Pharm Biol., 49:927-935.
Chendil D, Ranga RS, Meigooni D, Sathishkumar S, Ahmed MM. 2004. Curcumin confers radiosensitizing effect in prostate cancer cell line PC-3. Oncogene 23:1599-1607.
Coleman MC, Asbury CR, Daniels D, Du J, Aykin-Burns N, Smith BJ. 2008. 2-deoxy-D-glucose causes cytotoxicity, oxidative stress, and radiosensitization in pancreatic cancer. Free Radic Biol Med., 44:322-331.
Delaney G, Jacob S, Featherstone C, Barton M. 2005. The role of radiotherapy in cancer treatment: estimating optimal utilization from a review of evidence-based clinical guidelines. Cancer 104:1129-1137.
Dimitroulis J, Toubis M, Antoniou D, Marosis C, Armenaki U, Stathopoulos GP. 2006. Alternate paclitaxel-gemcitabine and paclitaxel-vinorelbine biweekly administration in non-small cell lung cancer patients: a phase II study. Anticancer Res., 26:1397-1402.
Ebrahim AS, Babu E, Thirunavukkarasu C, Sakthisekaran D. 2001. Protective role of vitamin E, 2-deoxy-D-glucose, and taurine on perchloroethylene induced alterations in ATPases. Drug Chem Toxicol. 24:429-437.
Eriksson D, Löfroth PO, Johansson L, Riklund K, Stigbrand T. 2009. Apoptotic signalling in HeLa Hep2 cells following 5 Gy of cobalt-60 gamma radiation. Anticancer Res. 29:4361-4366.
Essack M, Bajic VB, Archer JA. 2011. Recently confirmed apoptosis-inducing lead compounds isolated from marine sponge of potential relevance in cancer treatment. Mar Drugs 9:1580-1606.
Fenninger LD, Mider GB. 1954. In: Greenstein JP, Haddow A (ed) Advances in cancer research. Academic Press, New York. 244.
Gogvadze V, Orrenius S, Zhivotovsky B. 2008. Mitochondria in cancer cells: what is so special about them? Trends Cell Biol., 18:165-173.
Hazra B, Kumar B, Biswas S, Pandey BN, Mishra KP. 2005. Enhancement of the tumour inhibitory activity, in vivo, of diospyrin, a plant-derived quinonoid, through liposomal encapsulation. Toxicol Lett., 157:109-117.
Hori Y, Takamori Y, Nishio K. 1970. The Effects of X-Irradiation on Lactate Dehydrogenase Isozymes in Plasma and in Various Organs of Mice. Radiat Res. 43:143-151.
Javvadi P, Segan AT, Tuttle SW, Koumenis C. 2008. The chemopreventive agent curcumin is a potent radiosensitizer of human cervical tumor cells via increased reactive oxygen species production and overactivation of the mitogen-activated protein kinase pathway. Mol Pharmacol. 73:1491-1501.
Karthikeyan S, Kanimozhi G, Prasad NR, Mahalakshmi R. 2011. Radiosensitizing effect of ferulic acid on human cervical carcinoma cells in vitro. Toxicol In Vitro., 25:1366-1375.
Kim W, Seong KM, BuHyun Youn. 2011. Phenylpropanoids in radioregulation: double edged sword. Exp Mol Med. 43:323-333.
Lee YJ, Galoforo SS, Berns CM, Chen JC, Davis BH, Sim JE. 1998. Glucose deprivation-induced cytotoxicity and alterations in mitogen-activated protein kinase activation are mediated by oxidative stress in multidrug-resistant human breast carcinoma cells. J Biol Chem., 273:5294-5299.
Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ. 1951. Protein measurement with the Folin phenol reagent. J Biol Chem. 193:265-275.
Ma ZC, Hong Q, Wang YG, Tan HL, Xiao CR, Liang QD. 2011. Effects of ferulic acid on hematopoietic cell recovery in whole-body gamma irradiated mice. Int J Radiat Biol. 87:499-505.
Maschek G, Savaraj N, Priebe W, Braunschweiger P, Hamilton K, Tidmarsh GF. 2004. 2-deoxy-D-glucose increases the efficacy of adriamycin and paclitaxel in human osteosarcoma and non-small cell lung cancers in vivo. Cancer Res., 64:31-34.
Maurya DK, Nair CKK. 2006. Preferential radioprotection to DNA of normal tissues by ferulic acid under ex vivo and in vivo conditions in tumor bearing mice. Mol Cell Biochem. 285:181-190.
Mukherjee KL. 1988. Medical laboratory technology. a procedure manual for routine diagnostic tests. Tata McGraw Hill, New Delhi.
Munoz-Pinedo C, Ruiz-Ruiz C, Ruiz DA, Palacios C, Lopez-Rivas A. 2003. Inhibition of glucose metabolism sensitizes tumor cells to death receptor-triggered apoptosis through enhancement of death-inducing signaling complex formation and apical procaspase-8 processing. J Biol Chem., 278:12759-12768.
Ozaslan M, Karagoz ID, Kilic IH, Guldur ME. 2011. Ehrlich ascites carcinoma. Afr J Biotechnol., 10:2375-2378.
Park M, Song KS, Kim HK, Park YJ, Kim HS, Bae MI, Lee J. 2009. 2-Deoxy-d-glucose protects neural progenitor cells against oxidative stress through the activation of AMP-activated protein kinase. Neurosci Lett., 449:201-206.
Price VE, Greenfield RE. Anemia in cancer. In: Greenstein JP, Haddow A (ed) 1950. Advances in cancer research. Academic Press, New York. 199-200.
Rao SK, Rao PS, Rao BN. 2008. Preliminary investigation of the radiosensitizing activity of guduchi (Tinospora cordifolia) in tumor-bearing mice. Phytother Res., 22:1482-1489.
Reddy BV, Prasad NR. 2011. 2-deoxy-D-glucose combined with ferulic acid enhances radiation response in non-small cell lung carcinoma cells. Cent Eur J Biol., 6:743-755.
Sharma S, Guthrie PH, Chan SS, Haq S, Taegtmeyer H. 2007. Glucose phosphorylation is required for insulin-dependent mTOR signalling in the heart. Cardiovasc Res., 76:71-80.
Singh NP, McCoy MT, Tice RR, Schneider EL. 1988. A simple technique for quantification of low levels of DNA damage in individual cells. Exp Cell Res., 175:184-191.
Sinthupibulyakit C, Grimes KR, Domann FE, Xu Y, Fang F, Ittarat W. 2009. p53 is an important factor for the radiosensitization effect of 2-deoxy-D-glucose. Int J Oncol. 35:609-615.
Thornberry NA, Lazebnik Y. 1998. Caspases: Enemies within. Science 281:1312-1316.
Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. 2007. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol., 39:44-84.
Wroblewski F, LaDue JS. 1955. Lactic dehydrogenase activity in blood. Proc Soc Exp Biol Med., 90:210-213.
Zheng LF, Dai F, Zhou B, Yang L, Liu ZL. 2008. Prooxidant activity of hydroxycinnamic acids on DNA damage in the presence of Cu (II) ions: mechanism and structure-activity relationship. Food Chem Toxicol., 46:149-156.
Published
2012-07-14
How to Cite
Reddy, B. V., & Prasad, N. R. (2012). Radiosensitizing effects of 2-deoxy-D-glucose and ferulic acid on mouse Ehrlich’s Ascites Carcinoma in Swiss albino mice. Journal of Research in Biology, 2(5), 499-512. Retrieved from https://ojs.jresearchbiology.com/ojs1/index.php/jrb/article/view/242
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