Alpinia officinarum or lesser galangal (高良姜), is a member of the ginger family, which originates from China and is now cultivated throughout Southeast Asia (Figure 1). The roots are known as galangal and are used in cooking, perfumes and are also known for their medicinal properties. Alnus japonica or East Asian alder (日本桤木), is a species of tree found in Japan, Korea, and eastern China, stretching to Russia. Diarylheptanoids, the family of which the anti-cancer agent curcumin from turmeric is a member, can be extracted from these plants. Diarylheptanoid compounds from these medicinal plants were found to inhibit the growth of the PANC-1 (KRAS heterozygous G12D, TP53 homozygous P72R and R273H) pancreatic cancer cell line [1, 2]. The mechanism was proposed to derive from inhibiting the FoxM1 transcription factor signalling axis.
|Figure 1: Alpinia officinarum. Credit: Biodiversity Heritage Library. No changes were made. Creative Commons Attribution 2.0 Generic (CC BY 2.0).|
FoxM1 is a transcription factor of central importance to pancreatic cancer . It promotes the transcription of genes involved in cell cycle progression and cell survival as well as migration and invasion . FoxM1 transcription has been demonstrated to be promoted by the sonic hedgehog pathway in colorectal cancer and furthermore the hedgehog pathway is almost universally upregulated in pancreatic cancer [5, 6]. Dong et al. proposed that FoxM1 target genes are downregulated in response to the diarylheptanoid compounds due to Gli1/2 protein downregulation. Interestingly Stat3 signalling has been found to be downregulated by other diarylheptanoid compounds such as HO-3867 and Stat3 transcription can be indirectly upregulated by Gli1 via IL-6 [7, 8]. The extent to which different diarylheptanoid compounds could inhibit both FoxM1 and Stat3 axes in pancreatic cancer is an open question.
- Dong GZ, Jeong JH, Lee YI, Lee SY, Zhao HY, Jeon R, Lee HJ, Ryu JH. Diarylheptanoids suppress proliferation of pancreatic cancer PANC-1 cells through modulating shh-Gli-FoxM1 pathway. Arch Pharm Res. 2017 Apr;40(4):509-517. Doi: 10.1007/s12272-017-0905-2. PubMed PMID: 28258481.
- Gradiz R, Silva HC, Carvalho L, Botelho MF, Mota-Pinto A. MIA PaCa-2 and PANC-1 – pancreas ductal adenocarcinoma cell lines with neuroendocrine differentiation and somatostatin receptors. Sci Rep. 2016 Feb 17;6:21648. Doi: 10.1038/srep21648. PubMed PMID: 26884312.
- Akbari B, Mohammadnia A, Yaqubi M, Wee P, Mahdiuni H. Comprehensive Dissection of Transcriptome Data and Regulatory Factors in Pancreatic Cancer Cells. J Cell Biochem. 2017 Apr 12. doi: 10.1002/jcb.26053. PubMed PMID: 28401644.
- Quan M, Wang P, Cui J, Gao Y, Xie K. The roles of FOXM1 in pancreatic stem cells and carcinogenesis. Mol Cancer. 2013 Dec 10;12:159. Doi: 10.1186/1476-4598-12-159. Review. PubMed PMID: 24325450.
- Wang D, Hu G, Du Y, Zhang C, Lu Q, Lv N, Luo S. Aberrant activation of hedgehog signaling promotes cell proliferation via the transcriptional activation of forkhead Box M1 in colorectal cancer cells. J Exp Clin Cancer Res. 2017 Feb 2;36(1):23. doi: 10.1186/s13046-017-0491-7. PubMed PMID: 28148279.
- Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A, Hong SM, Fu B, Lin MT, Calhoun ES, Kamiyama M, Walter K, Nikolskaya T, Nikolsky Y, Hartigan J, Smith DR, Hidalgo M, Leach SD, Klein AP, Jaffee EM, Goggins M, Maitra A, Iacobuzio-Donahue C, Eshleman JR, Kern SE, Hruban RH, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008 Sep 26;321(5897):1801-6. Doi: 10.1126/science.1164368. PubMed PMID: 18772397.
- Hu Y, Zhao C, Zheng H, Lu K, Shi D, Liu Z, Dai X, Zhang Y, Zhang X, Hu W, Liang G. A novel STAT3 inhibitor HO-3867 induces cell apoptosis by reactive oxygen species-dependent endoplasmic reticulum stress in human pancreatic cancer cells. Anticancer Drugs. 2017 Apr;28(4):392-400. Doi: 10.1097/CAD.0000000000000470. PubMed PMID: 28067673.
- Mills LD, Zhang Y, Marler RJ, Herreros-Villanueva M, Zhang L, Almada LL, Couch F, Wetmore C, Pasca di Magliano M, Fernandez-Zapico ME. Loss of the transcription factor GLI1 identifies a signaling network in the tumor microenvironment mediating KRAS oncogene-induced transformation. J Biol Chem. 2013 Apr 26;288(17):11786-94. doi: 10.1074/jbc.M112.438846. PubMed PMID:23482563.