Catechin-vanilloid synergies with potential clinical applications in cancer
Dorothy M Morré1, D James Morré
1Department of Foods and Nutrition, Purdue University, West Lafayette, Indiana 47907-2059, USA. morredm@purdue.edu
Abstract:
A cancer-specific cell surface protein, tNOX, has been identified as a target for low-dose cell killing (apoptosis) of cancer cells by green tea catechins and Capsicum vanilloid combinations. This protein is uniquely associated with all forms of cancer and is absent from normal cells and tissues. Its activity is correlated with cancer growth. When blocked, cancer cells fail to enlarge after division and eventually die. Among the most potent and effective inhibitors of tNOX are naturally occurring polyphenols exemplified by the principal green tea catechin (-)-epigallocatechin gallate (EGCg) and the vanilloid capsaicin. Catechin-vanilloid combinations are 10 to 100 times more effective than either catechins or vanilloids alone. Vector-forced overexpression of tNOX cDNA and antisense has demonstrated that the tNOX target is both necessary and sufficient to explain the anticancer properties of green tea catechins alone and in vanilloid-containing combinations. The necessity and sufficiency of tNOX was validated as the catechin target with transgenic mice overexpressing the processed form of tNOX. Transgenic mice grew faster and the increased growth caused by tNOX overexpression was blocked by EGCg in the drinking water. A catechin-vanilloid mixture where one 350-mg capsule is equivalent to 16 cups of green tea in its ability to inhibit tNOX and growth of cancer cells in culture is undergoing clinical evaluation as a therapeutic aid for cancer patients.
Insights
Green tea catechins and capsaicin target the cancer-specific protein tNOX, inducing cancer cell death. Combinations of these natural compounds show significantly enhanced anticancer effects, offering a promising therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Natural Product Chemistry
Background:
- A novel cancer-specific cell surface protein, tNOX, is implicated in cancer cell growth and survival.
- tNOX activity correlates with tumor progression and is absent in normal tissues.
- Targeting tNOX presents a potential strategy for cancer therapy.
Purpose of the Study:
- To investigate the role of tNOX as a target for natural compounds in cancer treatment.
- To evaluate the synergistic anticancer effects of green tea catechins and vanilloids on tNOX.
- To validate tNOX as a necessary and sufficient target for these compounds' anti-cancer properties.
Main Methods:
- Utilized vector-forced overexpression of tNOX cDNA and antisense to demonstrate target necessity and sufficiency.
- Employed transgenic mice overexpressing processed tNOX to validate the target in vivo.
- Assessed the inhibitory effects of (-)-epigallocatechin gallate (EGCg) and capsaicin, individually and in combination, on tNOX activity and cancer cell growth.
Main Results:
- (-)-Epigallocatechin gallate (EGCg) and capsaicin were identified as potent inhibitors of tNOX.
- Catechin-vanilloid combinations were 10 to 100 times more effective than individual compounds.
- EGCg effectively blocked cancer growth in transgenic mice overexpressing tNOX.
- A catechin-vanilloid mixture demonstrated significant tNOX inhibition and cancer cell growth reduction in vitro.
Conclusions:
- tNOX is a validated target for the anticancer effects of green tea catechins and vanilloids.
- Combination therapy with catechins and vanilloids offers a potent and synergistic approach to cancer treatment.
- A catechin-vanilloid formulation is under clinical evaluation as an adjunct cancer therapy.
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