Sweet Flag (Acorus calamus) and Cancer (anticancer research): evidence and sources

Cancer is one of the major non-communicable diseases posing substantial challenges in both developing and developed countries. The options available for treatment of different cancer are associated with various limitations, including severe toxicity, drug resistance, poor outcomes and a high risk of relapse. Hence, an increased attention and necessity for screening of various phytochemicals from natural sources for superior and safer alternative has been ongoing for several decades. In recent years, phytochemicals like galantamine, erwinaze, rivastigmine, resveratrol from natural sources have been found to be important therapeutic targets for the treatment of various diseases including cancer, neurodegeneration, diabetes, and cardiovascular effects. Acorus calamus (Sweet flag), and/or its bioactive phytochemical alpha (α)-and beta (β)-asarone, is a well-known drug in the traditional system of medicine which possesses anti-tumor and chemo-preventive activities as evident from numerous pre-clinical studies both in-vitro and in-vivo . In this article, we critically review the current available scientific evidences of A. calamus and/or asarone for cancer chemoprevention based on preclinical in-vitro and in-vivo models. In addition, we also have compiled and discussed the molecular targets of mechanism(s) involved in the anti-cancer activity of A. calamus /asarone. Still, extensive in-vivo studies are necessary using various animal models to understand the molecular mechanism behind the pharmacological activity of the bioactive phytochemicals derived from A. calamus . It is strongly believed that the comprehensive evidence presented in this article could deliver a possible source for researchers to conduct future studies pertaining to A. calamus and/or its bioactive phytochemicals asarone for cancer chemoprevention.

Background β-asarone (β-as), a compound extracted from Acorus calamus, has been found to have anticancer effects on a variety of human cancers. However, the potential effect of β-as on bladder cancer (BCa) remains unknown. Methods After exposure to β-as, migration, invasion, and epithelial-mesenchymal transition (EMT) of BCa were determined by wound healing, transwell, and Western blot assays. Expression of proteins involved in the EMT and ER stress were explored by Western blot assays. Nude mouse xenograft model was served as the model system in vivo. Results The migration, invasion, and EMT of BCa were significantly inhibited after β-as treatment. Further experiments revealed that endoplasmic reticulum (ER) stress is involved in β-as-mediated metastasis inhibition. In addition, β-as significantly up-regulated activating transcription factor 6 (ATF6), a branch of ER stress, and promoted its Golgi cleavage and nuclear localization. ATF6 silencing attenuated β-as-mediated metastasis and EMT inhibition in BCa cells. Conclusion Our data suggests that β-as inhibits migration, invasion, and EMT of BCa by activating the ATF6 branch of ER stress. Thus, β-as represents a potential candidate for BCa treatment.

Esophageal cancer is one of the most common malignancies which induces cancer-related death. Cancer metastasis and recurrence are the main obstacle faced in esophageal cancer treatment. β-Asarone has been shown to act as an anti-cancer reagent in various cancer types. However, the anti-cancer activities of β-Asarone in esophageal cancer have not been shown. In the current study, we show that β-Asarone suppressed the proliferation of esophageal squamous cancer cells (ESCC) in both dose- and time-dependent manners. Moreover, β-Asarone treatment increases activated caspase 3, caspase 9, and cleaved poly ADP-ribose polymerase, and induces apoptosis in ESCC. Additionally, β-Asarone also suppresses epithelial-mesenchymal transition (EMT) and the invasive and migratory abilities in ESCC. Interestingly, β-Asarone suppresses TGF-β/Smad signaling by inhibition of TGF-β-induced phosphorylation of Smad2 and Smad3. Importantly, we show that inhibition of TGF-β/Smad signaling activation is critical for β-Asarone-suppressed EMT. Our data revealed a novel role of β-Asarone which targets invasive properties by inhibiting TGF-β/Smad signaling activation in ESCC. Our study suggests the potential application of β-Asarone to reduce cancer metastasis and recurrence in esophageal cancer treatment.

β -asarone is the main active ingredient of the Chinese herb Rhizoma Acori Tatarinowii, which exhibits a wide range of biological activities. It was confirmed to be an efficient cytotoxic agent against gastroenteric cancer cells. However, the exact mechanism of β -asarone in gastric cancer (GC) remains to be elucidated. The present study showed the inhibitory effect of β -asarone on three types of different differentiation stage GC cell lines (MGC803, SGC7901, and MKN74) in a dose-dependent manner. Meanwhile, the synergistic sensitivity of β -asarone and cisplatin was confirmed by using the median-effect principle. Flow cytometry assay revealed that under both normoxia and CoCl 2 -induced hypoxia conditions, β -asarone can induce apoptosis of GC cells, which can block GC cells in the cell cycle G2/M phase, showing obvious subdiploid peak. Moreover, the activity of lactic dehydrogenase (LDH), an enzyme that plays an important role in the final step of tumor glycolysis, was significantly decreased in GC cells following treatment with β -asarone. Mechanistically, β -asarone can reduce pyruvate dehydrogenase kinase (PDK) 1, phospho(p)-PDK1, PDK4, hypoxia-inducible factor 1- α (HIF1 α ), c-myc, STAT5, and p-STAT5 expression, which revealed how β -asarone affects tumor glycolysis. In conclusion, the present study provided evidence in support of the hypothesis that the increase of chemotherapy sensitization by β -asarone is associated with the inhibition of tumor glycolysis.

Objective Acorus calamus ( A. calamus ) has been used as a medicinal plant in Asia for its effects on digestive system for the last 2000 years. To investigate the anti-cancer activity of rhizome of A. calamus , the ethanolic and methanolic extracts and essential oil of the rhizome were prepared and their effects were assessed on human gastric cancer cell line (AGS). Materials and methods The viability of cells which were treated with the extracts and the essential oil was assessed by MTT assay. To evaluate the anti-angiogenic property of the extracts, in vitro tube formation assay was done. Cell cycle distribution and the expression of Oct4 and Nucleostemin, after treatments, were checked by flowcytometry and quantitative RT-PCR, respectively. Furthermore, analysis of essential oil from A.calamus was done by GC-MS. Results Our results showed that the growth of AGS cells was inhibited by the extracts and essential oil and the extracts inhibited the angiogenesis in HUVEC cells. Our data revealed that the extracts and essential oil of A. calamus caused G1 arrest in AGS cells and downregulation of Oct4 and NS after treatment. By GC-MS analysis, we found new compounds such as epiprezizaene, valencene and isocyclocitral in essential oil of A. Conclusion All together, our results showed that the extracts of A. calamus have anti-proliferative and anti-angiogenic effects on cancer cells.

β-Asarone is the main volatile oil of Chinese herb Rhizoma Acori Tatarinowii. It exhibits a wide range of biological activities in many human organs. However, few studies have investigated the effect of β-asarone on gastric cancer. The present study investigated the effect of β-asarone on the proliferation and apoptosis of three types of differentiated human gastric cancer cell lines (SGC-7901, BGC-823 and MKN-28) in vitro as well as the related molecular mechanisms. Methyl thiazolyl tetrazolium assay, Annexin V/PI double staining, immunofluorescence test and transmission electron microscopy all confirmed that β-asarone had an obvious dose-dependent inhibitive effect on the proliferation of human gastric cancer cells and induced apoptosis of the cell lines. Transwell invasion, wound-healing and matrix‑cell adhesion experiments confirmed that β-asarone inhibited the invasion, migration and adhesion of human gastric cancer BGC-823 cells. Quantitative real-time PCR and western blotting found that β-asarone significantly activated caspase-3, caspase-8, caspase-9, Bax, Bak and suppressed Bcl-2, Bcl-xL and survivin activity. Moreover, β-asarone increased the expression of RECK, E-cadherin and decreased the expression of MMP-2, MMP-9, MMP-14 and N-cadherin. The present study demonstrated that β-asarone effectively inhibits the proliferation of human gastric cancer cells, induces their apoptosis and decreased the invasive, migratory and adhesive abilities.