Abstract
Sutherlandia frutescens (L) R. Br. (Sutherlandia) is a South African botanical that is traditionally used to treat a variety of health conditions, infections and diseases, including cancer. We hypothesized Sutherlandia might act through Gli/ Hedgehog (Hh)-signaling in prostate cancer cells and used RNA-Seq transcription profiling to profile gene expression in TRAMPC2 murine prostate cancer cells with or without Sutherlandia extracts. We found 50% of Hh-responsive genes can be repressed by Sutherlandia ethanol extract, including the canonical Hh-responsive genes Gli1 and Ptch1 as well as newly distinguished Hh-responsive genes Hsd11b1 and Penk.
Highlights
More than 200,000 new cases of prostate cancer (PCa) are diagnosed and almost 30,000 men die of this disease every year in the United States [1]
The abnormally activated Hedgehog (Hh) signaling pathway leads to advanced PCa and metastasis, and is important as well for other cancers such as medulloblastoma, basal cell carcinoma, small cell lung cancer, colorectal cancer and pancreatic cancer [2,3,5,6,7]
Inhibitory in several PCa cell lines and found the administration of Sutherlandia to TRAMP mice decreases the incidence of poorly differentiated carcinoma [21]
Summary
More than 200,000 new cases of prostate cancer (PCa) are diagnosed and almost 30,000 men die of this disease every year in the United States [1]. Recurrence of prostate tumors is frequent and acquired resistance to traditional treatments is difficult to control. Novel approaches that can efficiently target and block the signaling pathways that lead to the recurrence, drug resistance and cancer progression are needed [2,3,4]. The abnormally activated Hedgehog (Hh) signaling pathway leads to advanced PCa and metastasis, and is important as well for other cancers such as medulloblastoma, basal cell carcinoma, small cell lung cancer, colorectal cancer and pancreatic cancer [2,3,5,6,7]. Blocking the activated Hh-signaling pathway in a prostate cancer xenograft model completely repressed growth of the aggressive PCa tumor. Inhibition of Hh-signaling pathway in other cancers has been shown to be an effective means to treat cancer. Vismodegib, a Hh-signaling inhibitor, has PLOS ONE | DOI:10.1371/journal.pone.0145507 December 28, 2015
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