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Gracilaria edulis extract induces apoptosis and inhibits tumor in Ehrlich ascites tumor cells in vivo.

Patra S, Muthuraman MS - BMC Complement Altern Med (2013)

Bottom Line: Intraperitoneally administration of EEGE to EAT-bearing mice helped to increase the lifespan of the animals significantly inhibited tumor growth and increased survival of mice.Extensive hematology, biochemistry and histopathological analysis of liver and kidney indicated that daily doses of EEGE up to 300 mg/kg for 35 days are well tolerated and did not cause hematotoxicity nor renal or hepatotoxicity.It was evident that the mechanism explains the apoptotic activity of the algae extract.

View Article: PubMed Central - HTML - PubMed

Affiliation: Medical University of the Americas, Charlestown, Nevis, West Indies. s.patra@mua.edu.

ABSTRACT

Background: Marine environment is inestimable for their chemical and biological diversity and therefore is an extraordinary resource for the discovery of new anticancer drugs. Recent development in elucidation of the mechanism and therapeutic action of natural products helped to evaluate for their potential activity.

Methods: We evaluated Gracilaria edulis J. Ag (Brown algae), for its antitumor potential against the Ehrlich ascites tumor (EAT) in vivo and in vitro. Cytotoxicity evaluation of Ethanol Extract of Gracilaria edulis (EEGE) using EAT cells showed significant activity. In vitro studies indicated that EEGE cytotoxicity to EAT cells is mediated through its ability to produce reactive oxygen species (ROS) and therefore decreasing intracellular glutathione (GSH) levels may be attributed to oxidative stress.

Results: Apoptotic parameters including Annexin-V positive cells, increased levels of DNA fragmentation and increased caspase-2, caspase-3 and caspase-9 activities indicated the mechanism might be by inducing apoptosis. Intraperitoneally administration of EEGE to EAT-bearing mice helped to increase the lifespan of the animals significantly inhibited tumor growth and increased survival of mice. Extensive hematology, biochemistry and histopathological analysis of liver and kidney indicated that daily doses of EEGE up to 300 mg/kg for 35 days are well tolerated and did not cause hematotoxicity nor renal or hepatotoxicity.

Conclusion: Comprehensive antitumor analysis in animal model and in Ehrlich Ascites Tumor cells was done including biochemical, and pathological evaluations indicate antitumor activity of the extract and non toxic in vivo. It was evident that the mechanism explains the apoptotic activity of the algae extract.

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Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) activities, Alkaline phosphatase, and LDH levels in serum from mice treated with different doses of EEGE. The results express the mean ± S.D. (n = 6/group). ANOVA was performed for statistical comparison among groups.
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Figure 9: Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) activities, Alkaline phosphatase, and LDH levels in serum from mice treated with different doses of EEGE. The results express the mean ± S.D. (n = 6/group). ANOVA was performed for statistical comparison among groups.

Mentions: After encouraging effect of EEGE in inhibiting cancer progression in vivo, we evaluated the undesired side effects of the i.p. administration of daily doses of 100, 200 and 300 mg/kg of EEGE for 35 days in healthy adult swiss albino mice. Drug toxicity was assessed by clinical signs of gross toxicity, behavioral changes and mortality, including hematological, biochemical and histopathological parameters. No animal death was observed in any of the groups during the experimental period of 35 days. No abnormal clinical signs or behavioral changes were observed in any of the groups, and changes in body weights of the EEGE-treated groups were not significantly different between any groups including the control group after 35-days of treatment period (Table 1). There were no significant changes in hematological parameters in the EEGE-treated groups (Table 2). Similarly, no significant differences were found between the EEGE-treated groups and the controls for the three blood chemical parameters evaluated (Figure 9), AST, ALT, ALP and LDH, which were within the physiological range of values expected for the method of blood collection [27]. These data indicate that daily intraperitoneal injections of EEGE at doses up to 300 mg/kg for 35 days did not cause hematotoxicity nor poses risks of renal or hepatotoxicity. At necropsy, no visible pathological changes were noted in the livers and kidneys of mice administered EEGE at 100, 200 and 300 mg/kg doses. Histological analysis of formaldehyde-fixed, paraffin embedded liver and kidney sections stained with hematoxylin and eosin showed normal architecture in all experimental groups. Livers of animals treated with different doses of EEGE showed no sign of necrosis, fatty degeneration, or inflammation (Figure 10a). Similarly, glomerulus structures, and proximal and distal tubules in kidneys showed normal architecture (Figure 10b), pointing out that EEGE did not cause toxicity to these organs.


Gracilaria edulis extract induces apoptosis and inhibits tumor in Ehrlich ascites tumor cells in vivo.

Patra S, Muthuraman MS - BMC Complement Altern Med (2013)

Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) activities, Alkaline phosphatase, and LDH levels in serum from mice treated with different doses of EEGE. The results express the mean ± S.D. (n = 6/group). ANOVA was performed for statistical comparison among groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4222716&req=5

Figure 9: Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) activities, Alkaline phosphatase, and LDH levels in serum from mice treated with different doses of EEGE. The results express the mean ± S.D. (n = 6/group). ANOVA was performed for statistical comparison among groups.
Mentions: After encouraging effect of EEGE in inhibiting cancer progression in vivo, we evaluated the undesired side effects of the i.p. administration of daily doses of 100, 200 and 300 mg/kg of EEGE for 35 days in healthy adult swiss albino mice. Drug toxicity was assessed by clinical signs of gross toxicity, behavioral changes and mortality, including hematological, biochemical and histopathological parameters. No animal death was observed in any of the groups during the experimental period of 35 days. No abnormal clinical signs or behavioral changes were observed in any of the groups, and changes in body weights of the EEGE-treated groups were not significantly different between any groups including the control group after 35-days of treatment period (Table 1). There were no significant changes in hematological parameters in the EEGE-treated groups (Table 2). Similarly, no significant differences were found between the EEGE-treated groups and the controls for the three blood chemical parameters evaluated (Figure 9), AST, ALT, ALP and LDH, which were within the physiological range of values expected for the method of blood collection [27]. These data indicate that daily intraperitoneal injections of EEGE at doses up to 300 mg/kg for 35 days did not cause hematotoxicity nor poses risks of renal or hepatotoxicity. At necropsy, no visible pathological changes were noted in the livers and kidneys of mice administered EEGE at 100, 200 and 300 mg/kg doses. Histological analysis of formaldehyde-fixed, paraffin embedded liver and kidney sections stained with hematoxylin and eosin showed normal architecture in all experimental groups. Livers of animals treated with different doses of EEGE showed no sign of necrosis, fatty degeneration, or inflammation (Figure 10a). Similarly, glomerulus structures, and proximal and distal tubules in kidneys showed normal architecture (Figure 10b), pointing out that EEGE did not cause toxicity to these organs.

Bottom Line: Intraperitoneally administration of EEGE to EAT-bearing mice helped to increase the lifespan of the animals significantly inhibited tumor growth and increased survival of mice.Extensive hematology, biochemistry and histopathological analysis of liver and kidney indicated that daily doses of EEGE up to 300 mg/kg for 35 days are well tolerated and did not cause hematotoxicity nor renal or hepatotoxicity.It was evident that the mechanism explains the apoptotic activity of the algae extract.

View Article: PubMed Central - HTML - PubMed

Affiliation: Medical University of the Americas, Charlestown, Nevis, West Indies. s.patra@mua.edu.

ABSTRACT

Background: Marine environment is inestimable for their chemical and biological diversity and therefore is an extraordinary resource for the discovery of new anticancer drugs. Recent development in elucidation of the mechanism and therapeutic action of natural products helped to evaluate for their potential activity.

Methods: We evaluated Gracilaria edulis J. Ag (Brown algae), for its antitumor potential against the Ehrlich ascites tumor (EAT) in vivo and in vitro. Cytotoxicity evaluation of Ethanol Extract of Gracilaria edulis (EEGE) using EAT cells showed significant activity. In vitro studies indicated that EEGE cytotoxicity to EAT cells is mediated through its ability to produce reactive oxygen species (ROS) and therefore decreasing intracellular glutathione (GSH) levels may be attributed to oxidative stress.

Results: Apoptotic parameters including Annexin-V positive cells, increased levels of DNA fragmentation and increased caspase-2, caspase-3 and caspase-9 activities indicated the mechanism might be by inducing apoptosis. Intraperitoneally administration of EEGE to EAT-bearing mice helped to increase the lifespan of the animals significantly inhibited tumor growth and increased survival of mice. Extensive hematology, biochemistry and histopathological analysis of liver and kidney indicated that daily doses of EEGE up to 300 mg/kg for 35 days are well tolerated and did not cause hematotoxicity nor renal or hepatotoxicity.

Conclusion: Comprehensive antitumor analysis in animal model and in Ehrlich Ascites Tumor cells was done including biochemical, and pathological evaluations indicate antitumor activity of the extract and non toxic in vivo. It was evident that the mechanism explains the apoptotic activity of the algae extract.

Show MeSH
Related in: MedlinePlus