Introduction: Germacrone is a natural product isolated from Rhizoma curcuma with anti-tumor, anti-inflammatory, and anti-bacterial properties. Previous studies have demonstrated that Germacrone exhibits anti-tumor effect in breast and hepatoma cancer cell lines but the studies of its molecular mechanisms and anti-tumor properties in other cancers are not well studied. This study aims to investigate the anti-tumor effect of Germacrone on human skin, cervix, and gastric cancer cell lines and the molecular mechanism underlying the anti-tumor effect of Germacrone. Methods: A375 (skin malignant melanoma), AGS (gastric adenocarcinoma), and HeLa 229 (cervix adenocarcinoma) cell lines were employed for this research. Treatment of the cell lines with Germacrone has inhibited the cell proliferation in a dose-dependent manner as assessed by MTT assay. The cell lines were incubated with Germacrone for 24 hours followed by detection of the expression of BAX, BAK, p53, BCL2, MCL1, and BCL-XL using Real-time PCR. Results: Results from Real-time PCR has showed that pro-apoptotic gene BAK was highly expressed in all the human cell lines after the treatment with Germacrone. Furthermore, the expression of pro-apoptotic gene p53 were elevated in both A375 and HeLa 229 cell lines but not inAGS cell lines. The expression level of pro-survival genes BCL2 and MCL1 were found to be decreased in both AGS and A375 cell lines. Conclusion: In conclusion, Germacrone might be a potent anti-tumor drug candidate for Human Melanoma, Cervix Adenocarcinoma, and Gastric Adenocarcinoma by increasing the expression level of pro-apoptotic proteins BAK. Future studies will focus on studying the cytotoxicity effect of combination of Germacrone with standard chemotherapy drugs on Human Melanoma, Cervix Adenocarcinoma, and Gastric Adenocarcinoma.
Introduction: The Hedgehog (Hh) pathway serves as a major regulator in organ development, stem cell maintenance, cell proliferation, and cell differentiation. This pathway is highly regulated and aberrant activation will promote tumorigenesis. Hh pathway notably Sonic Hedgehog pathway was reported to be upregulated and promote tumorigenesis in various human malignancies including colorectal, gastric, lung, prostate, and breast. This review was aimed to discuss the current understanding of Hh pathway activation in different types of human cancers and discuss the development of the therapeutic applications targeting Hh pathway. Methods: A systematic review was conducted using the electronic research database PubMed Central (PMC) from 2014-2019. The search was limited to studies that are relevant to both Hh signalling pathway and human cancers. A total of 50 articles were selected and their references cited were searched and reviewed. Results: The results regarding the role of Hh signalling in pancreatic cancer and colorectal cancer are controversial with some reporting tumor promoting activities whereas others tumor suppressive activity. Besides, results from other studies suggesting that Hh signalling pathway plays an oncogenic role by inducing tumor cells proliferation, promoting metastasis and maintaining cancer stem cells in human cancers such as lung, stomach, and breast. To date, Glasdegib (PF-04449913) is the only Hh targeting small molecule inhibitor being studied at FDA Phase 3 clinical trial. Identification of the right tumors and minimization of the side effects remain as the main obstacles in the development of Hh signalling inhibitors. Conclusion: In conclusion, advancement in our understanding of Hh pathway has provided us opportunity to develop novel therapeutic strategies to fight human cancers with activated Hh pathway but more studies need to be conducted to solve the controversial regarding the role of Hh pathway in certain cancers.