Abstract 2246: Steam distilled ginger extract inhibits endometrial cancer cell proliferation by activating P53 and causing apoptosis.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Phenolic compounds present in dry ginger powder or solvent extracts of ginger roots induce cell cycle arrest and apoptosis in skin, breast, prostate, colon, and ovarian cancer cells. Another class of bioactive compounds, the terpenes, can be isolated by steam distillation of the ginger rhizomes. In this study, we examine the anti-cancer properties of Steam Distilled Ginger Extracts (SDGE) on endometrial cancer cells. SDGE at an IC-50 of 1.5 micrograms/ml inhibited the proliferation of two endometrial cancer cell lines, ECC-1 and Ishikawa. Decreased proliferation of Ishikawa and ECC-1 cells was a direct result of SDGE-induced-apoptosis as demonstrated by Annexin V FITC staining and increased expression of cleaved caspase 3. GC-MS analysis allowed us to identify 22 distinct terpenes in SDGE. Gingerols and other non-terpene phenolic compounds were not present in SDGE. Neral and Geranial constituted 25-35% of the total SDGE terpenes and were found to inhibit endometrial cancer cell proliferation. On the other hand, camphene and α-pinene, which together constitute 10% of SDGE, showed no effect on the proliferation of ECC-1 and Ishikawa cells. SDGE at concentrations as low as 25 nanograms/ml caused a rapid increase in intracellular calcium levels and an approximate decrease of 20% in the mitochondrial membrane potential. Ser-15 of p53 was phosphorylated after a 15 minute treatment of the cancer cells with SDGE (250 nanograms/ml). This activation of p53 was associated with a 90% decrease in Bcl2, whereas no effect was observed on Bax. Pifithrin-α, an inhibitor of p53, attenuated the anti-cancer effects of SDGE that result from apoptosis. In addition, SDGE (1.5 microgram/ml) was unable to induce apoptosis in the p53-negative ovarian cancer cell line, SKOV3. Our data therefore indicates that specific terpenes present in SDGE are highly efficient in controlling the growth of p53-expressing cancer cells. We therefore propose that SDGE and its constituent bioactive terpenes should be further investigated as anti-cancer agents. Citation Format: Yang Liu, Rebecca J. Whelan, Bikash R. Pattnaik, Kai David Ludwig, Rosalina V. Landeros, Enkateswar Subudhi, Helen Rowland, Nicholas Claussen, Noah Zucker, Shitanshu Uppal, David M. Kushner, Mildred Felder, Manish S. Patankar, Arvinder K. Kapur. Steam distilled ginger extract inhibits endometrial cancer cell proliferation by activating P53 and causing apoptosis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2246. doi:10.1158/1538-7445.AM2013-2246