Unravelling the anticancer efficacy of 10-oxo-7-epidocetaxel: in vitro and in vivo results.

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Unravelling the anticancer efficacy of 10-oxo-7-epidocetaxel: in vitro and in vivo results.

Drug Dev Ind Pharm. 2019 Jan 01;:1-11

Authors: Manjappa AS, Ramachandra Murthy RS

Abstract
PURPOSE: To prepare 7-epidocetaxel (7ED) and 10-oxo-7-epidocetaxel (10-O-7ED) formulations as like marketed Taxotere® (TXT) injection and to screen them for in vitro and in vivo anticancer efficacy including their in vivo toxicity behavior.
METHODS: The 7ED and 10-O-7ED formulations were screened for in vitro anti-proliferative, anti-metastatic and cell cycle arresting behaviors. Further, in vivo acute toxicity of TXT injection containing 10% of 7ED and 10-O-7ED separately and the therapeutic study of 10-O-7ED alone were studied in B16F10 experimental metastasis mouse model.
RESULTS: 10-O-7ED caused significantly higher cytotoxicity after 48 and 72 h than 22 h study. 10-O-7ED showed significantly increased in vitro anti-metastatic activity than TXT. The TXT caused more arrest of cells at S phase, whereas 10-O-7ED arrested more at G2-M phase and vice versa at higher concentration. In vivo acute toxicity study revealed better therapeutic effect with reduced toxicity of TXT containing 10% 10-O-7ED than TXT alone. Similarly, the therapeutic study revealed significantly less number of surface metastatic nodules formation with 10-O-7ED treated group (107 ± 49) (***p < .0001) than control group (348 ± 56). Also, the control group showed significant weight loss at the end (20th day) of the experiment (*p < .05, p = .041) than 10-O-7ED treated group which showed about 4% increased mean group weight.
CONCLUSION: Our study revealed the significantly higher in vivo anti-metastatic behavior, with no toxicity, of 10-O-7ED. However, it is a preliminary observation being noticed but further investigations are needed to address the potential of 10-O-7ED in cancer treatment with mechanisms behind the improved therapeutic efficacy with no toxicity.

PMID: 30599774 [PubMed - as supplied by publisher]

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