Date of Award

2014

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Chemistry and Biochemistry

First Advisor

Pandey, Siyaram

Keywords

Apoptosis, Autophagy, Cancer, Caspases, Natural health products

Rights

CC BY-NC-ND 4.0

Abstract

The incidence of cancer worldwide is continuously on the rise, and the death toll associated with cancer, is constantly increasing. Available cancer therapy is unable to combat this ever-changing disease, and the severe side effects associated with various forms of therapy, indicate a serious need for the development of more effective and safer alternatives to currently available treatment. The use of natural health products in disease treatment has contributed to the development of over 75% of available chemotherapy. In this thesis, we study the potential anti-cancer effect of two natural health products, dandelion root and long pepper extracts. The major objectives of this work were to; - Evaluate the efficacy and mechanism of these extracts in various cancer models, - Assess any potential safety and toxicity issues associated with the use of these extracts and, - De-convolute and identify the pharmacologically active components that contribute to the anti-cancer activity of these extract Using standard biochemical and morphological assays, the induction of various programmed cell death processes was assessed, following treatment in cancer and non-cancer cell models, as well as in animal models. The results obtained indicate that dandelion root and long pepper extracts were efficacious in selectively inducing apoptosis and pro-death autophagy in various cancer cell models. Dandelion root extract rapidly activated the extrinsic pathway of apoptosis, a situation that was crucial to apoptosis induction in leukemia cells, but not required for colorectal cancer cells. Gene expression analysis showed that dandelion root extract efficiently targets multiple pathways to promote its anti-cancer activity. The generation of reactive oxygen species by long pepper extract treatment, appeared to be partially responsible for the induction of apoptosis in cancer cells. Furthermore, the lack of toxicity observed in animal models, on oral administration regimens of dandelion root and long pepper extracts, further confirm the safety of these extracts. Interestingly, the same regimen of oral administration of these extracts was successful in halting the growth of colon tumors in xenograft models. These findings provide scientific validation concerning the safe and effective use of natural health products as non-toxic and potentially more efficacious forms of therapy.

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