Abstract LB-171: Throwing the 'book' at the cancer cell speciifically: A new paradigm and a new strategy for cancer prevention and cure

Abstract

Abstract There are numerous reports of natural compounds that act on cancer pathways. These compounds work at high micromolar concentrations that cannot be achieved under in vivo conditions. Toxic side effects are a concern when such high concentrations are used. Also synergism between different natural compounds have been explored using 2 or 3 compounds together, but these have still not been able to kill 100% of the cancer cells. To develop the new paradigm, we considered general features common to several cancers viz. proliferation (due to cell cycle changes), survival of cancer cell & metastasis controlling pathways. In addition pathways involved in programmed cell death (apoptosis) were given consideration. We chose 6 natural compounds & created a ‘phytochemical super cocktail’ capable of killing 100% of breast cancer cells (MCF7, MDA-MB-231) in tissue culture, by simultaneously affecting all of the above mentioned pathways( J.Cancer 4, 703-715, 2013 ). The super cocktail had no effect on normal cells ( mesenchymal stem cells, NIH 3T3 cells, normal mammary epithelial cells). However, many of these compounds are lipophilic and not hydrophyllic, thus having poor absorption resulting in low bioavailability. By inclusion in the super cocktail, we demonstrated that the synergism between compounds can be extended to a degree wherein bioavailable/bioachievable levels also become effective levels that can kill cancer cells, without affecting normal cells. This represents a new strategy to achieve the effects predicted by the paradigm which can be used now to prevent/cure cancers. We now have demonstrated that it can be applied to several cancers; as examples, we have successfully killed BRCA1 mutation carrying breast cancer cells (SUM-149, separate abstract submitted).using the super cocktail. Here we show that it can kill prostate cancer cells(PC3), & non-small cell lung cancer cells in a dose dependent manner, using proliferation assay. These data will be presented to demonstrate the usefulness of this new approach immediately to prevent/cure cancers. We have already shown the efficacy of C-phycocyanin, one the compounds in the super cocktail, to prevent mammary tumor formation in rats ( induced by dimethyl benzanthracene). Inclusion of spirulina extract in the diet reduced the mortality from 85% to about 13% (Am.Jour.Pathol 184, 296-303, 2014 ) & induced lysis of formed tumors. However C-phycocyanin, the active compound of spirulina, by itself was not fully effective in killing human breast cancer cells, unlike the super cocktail. This indicates a greater in vivo efficacy of the super cocktail & we are planning to evaluate the same in the mouse xenograft model. At this writing, 750 women (normal and breast cancer bearing) have used the super cocktail as a nutritional supplement over the past 2 years without a single report of adverse reactions or toxicity. Support: Louisiana Cancer Research Consortium. Citation Format: Madhwa H. Raj, Shubha K. Ireland, Hector Biliran, Shailaja G. Raj. Throwing the 'book' at the cancer cell speciifically: A new paradigm and a new strategy for cancer prevention and cure [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-171. doi:10.1158/1538-7445.AM2017-LB-171