Abstract
Purpose: To investigate the effect of 2-[(4-hydroxy-phenylamino)-methylene]-5,5-dimethyl-cyclohex (HPDH) on mammary carcinogenesis induced by 7,12-dimethylbenz(a)anthracene in female Sprague Dawley rats.Methods: Among three groups of rats (50 each) used in the study, the control group was fed standard diet alone, ibuprofen group received standard diet containing 1200 mg/kg ibuprofen while HPDH group was administered standard diet containing 1200 mg/kg HPDH. The treatment was for 10 days for all the groups. All the animals received 20 mg of DMBA intragastrically by gavage. Clinical parameters for the rats were recorded weekly. Micrometer caliper was used to measure the diameter of all the tumors at the end of the experiment and tumor volume calculated. Histological evaluation was performed using hematoxylin and eosin (H&E) staining. High performance liquid chromatography (HPLC) was used to determine the level of HPDH and ibuprofen in the serum of the animals.Results: The data revealed a significant decrease in the number of rats with mammary tumor, number of tumors/rat and tumor volume by 54, 72 and 75 %, respectively, in HPDH group compared to control group. The ibuprofen- treated rats also showed significant decrease in the number of rats with tumor, number of tumors/rat and tumor volume by 43, 55, and 59 %, respectively. Treatment of rats with HPDH increased the latency period of tumor induction significantly (p < 0.005). Median detection period (50 % of tumors) was 92, 83 and 56 days, respectively, in HPDH, ibuprofen and control groups, respectively, after DMBA induction.Conclusion: These results demonstrate that HPDH possesses strong chemopreventive activity against mammary carcinogenesis.Keywords: Carcinogenesis, Mammary tumor, Median detection period, Tumor, Latency period, Chemopreventive activity, Ibuprofen
Highlights
In Western countries breast cancer is a most frequent malignant neoplasm among women
Animal studies have demonstrated the effects of NSAIDs on mammary carcinogenesis [7,8] and in our laboratories, the common overthe-counter drug ibuprofen produced highly significant reductions in tumor size and tumor burden associated with inhibition of the genetic expression of COX isoforms [9,10,11]
The observed chemopreventive effects of the HPDH exceeded those of the ibuprofen as well as other agents like retinoic acid 4-HPR and the glucuronidase inhibitor glucarate [16] that have shown significant antitumor effects in this animal model, but were slightly less than those of celecoxib [17]
Summary
In Western countries breast cancer is a most frequent malignant neoplasm among women. A typical example of the important role played by the enamide moiety in the biological activity of natural products is represented by the comparison of the IC50 of the potent anti-cancer agent salicylihalamide A, with two analogues. In view of the biological activity of salicylihalamide A, and similar functionality of test drug, the effect of HPDH (Fig 1) in mammary carcinogenesis in female Sprague Dawley rats was investigated in this study. The animals were palpated twice a week for detection of mammary tumors after 28 days of DMBA treatment. Descriptive statistics on body weights, tumor latency, number of rats with tumor, number of tumors per rat, and tumor volumes were examined and compared among the control, HPDH and treatment groups. P < 0.05 was taken to represent a statistically significant difference
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