Antineoplastic activities of MT81 and its structural analogue in Ehrlich ascites carcinoma-bearing Swiss Albino mice

Abstract

Many fungal toxins exhibit in vitro and in vivo antineoplastic effects on various cancer cell types. Luteoskyrin,a hydroxyanthraquinone has been proved to be a potent inhibitor against Ehrlich ascites tumor cells. The comparative antitumor activity and antioxidant status of MT81 and its structural analogue [Acetic acid-MT81 (Aa-MT81)] having polyhydroxyanthraquinone structure were assessed against Ehrlich ascites carcinoma (EAC) tumor in mice. The in vitro cytotoxicity was measured by the viability of EAC cells after direct treatment of the said compounds. In in vivo study, MT81 and its structural analogue were administered (i.p.) at the two different doses (5, 7 mg MT81; 8.93, 11.48 mg Aa-MT81/kg body weight) for 7 days after 24 hrs. of tumor inoculation. The activities were assessed using mean survival time (MST), increased life span (ILS), tumor volume, viable tumor cell count, peritoneal cell count, protein percentage and hematological parameters. Antioxidant status was determined by malondialdehyde (MDA) and reduced glutathione (GSH) content, and by the activity of superoxide dismutase (SOD) and catalase (CAT). MT81 and its structural analogues increased the mean survival time, normal peritoneal cell count. They decreased the tumor volume, viable tumor cell count, hemoglobin percentage and packed cell volume. Differential counts of WBC, total counts of RBC & WBC that altered by EAC inoculation, were restored in a dose-dependent manner. Increased MDA and decreased GSH content and reduced activity of SOD, and catalase in EAC bearing mice were returned towards normal after the treatment of MT81 and its structural analogue. Being less toxic than parent toxin MT81, the structural analogue showed more prominent antineoplastic activities against EAC cells compared to MT81. At the same time, both compounds exhibit to some extent antioxidant potential for the EAC-bearing mice.

Figure 1

Inhibitory role of MT81 on the body weight change in EAC-bearing mice. Data given are Mean ± SEM; n = 6. *significant different at p < 0.05, **significant different at p < 0.01, ***significant different at p < 0.001; EAC Control and Vehicle Control are compared to Saline control; Treated groups are compared to Vehicle Control by one-way ANOVA followed by Student’s t-test.

Figure 2

Inhibitory role of AaMT81 on the body weight change of EAC-bearing mice. Data given are Mean ± SEM; n = 6. *significant different at p < 0.05, **significant different at p < 0.01, ***significant different at p < 0.001; EAC Control and Vehicle Control are compared to Saline control; Treated groups are compared to Vehicle Control by one-way ANOVA followed by Student’s t-test.

Figure 3

Modulatory role of MT81 and AaMT81 on Mean Survival Time of EAC-bearing mice. Data given are Mean ± SEM; n = 6. *significant different at p < 0.05, **significant different at p < 0.01, ***significant different at p < 0.001; EAC Control and Vehicle Control are compared to Saline control; Treated groups are compared to Vehicle Control by one-way ANOVA followed by Student’s t-test.

Figure 4

Inhibition of Tumor Volume of EAC-bearing mice by MT81 and AaMT81. Data given are Mean ± SEM; n = 6. *significant different at p < 0.05, **significant different at p < 0.01, ***significant different at p < 0.001; oryEAC Control and Vehicle Control are compared to Saline control; Treated groups are compared to Vehicle Control by one-way ANOVA followed by Student’s t-test.

Figure 5

Inhibition of Viable Tumor Cell Count of EAC-bearing mice by MT81 and AaMT81 on Data given are Mean ± SEM; n = 6. *significant different at p < 0.05, **significant different at p < 0.01, ***significant different at p < 0.001; EAC Control and Vehicle Control are compared to Saline control; Treated groups are compared to Vehicle Control by one-way ANOVA followed by Student’s t-test.

Figure 6

Increase of Peritoneal Cell Count of EAC-bearing mice by MT81 and AaMT81 on. Data given are Mean ± SEM; n = 6. *significant different at p < 0.05, **significant different at p < 0.01, ***significant different at p < 0.001; EAC Control and Vehicle Control are compared to Saline control; Treated groups are compared to Vehicle Control by one-way ANOVA followed by Student’s t-test.

Figure 7

Modulatory role of MT81, AaMT81 on Neutrophil Count of EAC-bearing mice. Data given are Mean ± SEM; n = 6. *significant different at p < 0.05, **significant different at p < 0.01, ***significant different at p < 0.001; EAC Control and Vehicle Control are compared to Saline control; Treated groups are compared to Vehicle Control by one-way ANOVA followed by Student’s t-test.

Figure 8

Modulatory role of MT81, AaMT81 on Eosinophil Count of EAC-bearing mice. Data given are Mean ± SEM; n = 6. *significant different at p < 0.05, **significant different at p < 0.01, ***significant different at p < 0.001; EAC Control and Vehicle Control are compared to Saline control; Treated groups are compared to Vehicle Control by one-way ANOVA followed by Student’s t-test.

Figure 9

Modulatory role of MT81, AaMT81 on Lymphocyte Count of EAC-bearing mice. Data given are Mean ± SEM; n = 6. *significant different at p < 0.05, **significant different at p < 0.01, ***significant different at p < 0.001; EAC Control and Vehicle Control are compared to Saline control; Treated groups are compared to Vehicle Control by one-way ANOVA followed by Student’s t-test.

Figure 10

Modulatory role of MT81, AaMT81 on Monocyte Count of EAC-bearing mice. Data given are Mean ± SEM; n = 6. *significant different at p < 0.05, **significant different at p < 0.01, ***significant different at p < 0.001; EAC Control and Vehicle Control are compared to Saline control; Treated groups are compared to Vehicle Control by one-way ANOVA followed by Student’s t-test.

Figure 11

Role of MT81, AaMT81 on Packed Cell Volume (PCV) of EAC-bearing mice. Data given are Mean ± SEM; n = 6. *significant different at p < 0.05, **significant different at p < 0.01, ***significant different at p < 0.001; EAC Control and Vehicle Control are compared to Saline control; Treated groups are compared to Vehicle Control by one-way ANOVA followed by Student’s t-test.

Figure 12

Role of MT81, AaMT81 on Proteins% of EAC-bearing mice. Data given are Mean ± SEM; n = 6. *significant different at p < 0.05, **significant different at p < 0.01, ***significant different at p < 0.001; EAC Control and Vehicle Control are compared to Saline control; Treated groups are compared to Vehicle Control by one-way ANOVA followed by Student’s t-test.

Figure 13

MDA content of EAC-bearing mice after the treatment of MT81 and AaMT81. Data given are Mean ± SEM; n = 6. *significant different at p < 0.05, **significant different at p < 0.01, ***significant different at p < 0.001; EAC Control and Vehicle Control are compared to Saline control; Treated groups are compared to Vehicle Control by one-way ANOVA followed by Student’s t-test.

Figure 14

Glutathione content of EAC-bearing mice after the treatment of MT81 and AaMT81. Data given are Mean ± SEM; n = 6. *significant different at p < 0.05, **significant different at p < 0.01, ***significant different at p < 0.001; EAC Control and Vehicle Control are compared to Saline control; Treated groups are compared to Vehicle Control by one-way ANOVA followed by Student’s t-test.

Figure 15

SOD activity of EAC-bearing mice after the treatment of MT81 and AaMT81. Data given are Mean ± SEM; n = 6. *significant different at p < 0.05, **significant different at p < 0.01, ***significant different at p < 0.001; EAC Control and Vehicle Control are compared to Saline control; Treated groups are compared to Vehicle Control by one-way ANOVA followed by Student’s t-test.

Figure 16

Catalase activity of EAC-bearing mice after the treatment of MT81 and AaMT81. Data given are Mean ± SEM; n = 6. *significant different at p < 0.05, **significant different at p < 0.01, ***significant different at p < 0.001; EAC Control and Vehicle Control are compared to Saline control; Treated groups are compared to Vehicle Control by one-way ANOVA followed by Student’s t-test.

Figure 17

Possible potential anti-neoplastic cellular pathways of MT81 and AaMT81 on EAC-bearing mice. Where ‘+’ denoted to stimulatory and ‘−’ denoted to inhibitory effects to the respective parameters.