<em>Hedychium coronarium</em>&nbsp;extract arrests cell cycle progression, induces apoptosis, and impairs migration and invasion in HeLa cervical cancer cells

Abstract

BackgroundHedychium coronarium Koen. (Zingiberaceae) is traditionally used as medicine in countries such as India, China, and Vietnam for treatment of various ailments including cancer. However, in spite of its implied significance in cancer treatment regimes, there are no reports so far involving the anticancerous attributes of H, coronarium ethanol extract (HCEE) on cancer cells and a more comprehensive study on its mechanism is still lacking.Materials and methodsThe cytotoxicity of HCEE was evaluated by MTT and clonogenic survival assay. Annexin V/propidium iodide (PI), Hoechst 33342 staining, and TUNEL assay were performed to detect apoptosis. Cell cycle analysis was performed using PI staining. JC-1 and 2′,7′-dichlorodihydrofluorescein diacetate assay were used to check the levels of MMP and ROS, respectively. Western blot analysis was carried out to measure the expression levels of proteins. Migration and invasion activity were assessed by wound healing and Transwell membrane assay, respectively.ResultsAntiproliferative effect of HCEE was investigated in various cancerous and normal cell lines. Among these, HCEE significantly inhibited the survival of HeLa cells without affecting the viability of normal human umbilical vein endothelial cells. Annexin V/PI, Hoechst staining, and TUNEL assay showed HCEE induced apoptosis in HeLa cells in a dose-dependent manner. HCEE promoted cell cycle arrest at G1 phase in HeLa cells by upregulating the levels of p53 and p21 and downregulating the levels of cyclin D1, CDK-4, and CDK-6. Moreover, HCEE treatment upregulated the expression of Bax and downregulated the expression of Bcl-2. Additionally, HCEE activated the caspase cascade by increasing the activities of caspase-9, caspase-8, and caspase-3. The expression levels of Fas ligand and Fas were also upregulated. Further, HCEE inhibited the migratory potential of HeLa cells by downregulating MMP-2 and MMP-9 expression levels.ConclusionOur results indicate H. coronarium exerts antiproliferative and apoptotic effects against HeLa cells, and therefore may be used for treatment against cervical cancer.

Coronarin D Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Line

“…Popularly known as white garland-lily, butterfly lily, napoleon, narcissus, Olympia, white ginger or "lírio do brejo" (in Brazil), the H. coronarium rhizomes are used as a starch source [17] and in traditional medicine for treatment of inflammation, diabetes, and rheumatic pain, among other uses [15]. Among pharmacological evaluations, the ethanolic extract of H. coronarium rhizomes induces apoptosis on HeLa cells by promoting cell cycle arresting at G1 phase, upregulating p53, p21, and Bax expression as well as downregulating cyclin D1, cyclin-dependent kinases CDK-4, CDK-6, and Bcl-2 expression [18]. Moreover, chemical evaluation of these extracts afforded the isolation of several labdane-like diterpenes with anti-inflammatory action [19,20], antiallergic [21], antibacterial [22], and cytotoxic effects over A-549-lung cancer, SK-N-SH-human neuroblastoma, MCF-7 breast cancer, and HeLa cervical cancer cell lines [23].…”

Phytochemical and Pharmacological Support for the Traditional Uses of Zingiberacea Species in Suriname - A Review of the Literature

“…122 The cell growth inhibitory effects were in some cases accompanied by cell cycle arrest at the G 1 phase and signs of apoptosis. 123 In addition, several coronarin labdane diterpenes as well as benzoyl eugenol showed meaningful cancer chemopreventive activity in in vitro assays, inhibiting NF-κB, COX-1 and COX-2 activities, the induction of antioxidant response element, and cell proliferation. 124…”

“…Microbial infections, parasitic infections, inflammatory complaints, cancer 104,105 Labdane diterpenes such as, coronarins, farnesane sesquiterpenes such as nerolidol and hedychiols, monoterpenes such as 1,8-cineole and α-and β-pinene [107][108][109] Antimicrobial, [110][111][112][113][114][115] antiparasitic, 112,115,116 antiinflammatory and analgesic, [117][118][119][120] anticancer and chemopreventive activity 111,[121][122][123][124] Kaempferia galanga (L.)…”

“…Potential anticancer activity of H. coronarium is supported by the cytotoxicity of a partially purified rhizome extract against brine shrimp nauplii 111 , as well as that of several coronarins and their derivatives isolated from the rhizome against cultured human and animal cancer cell lines. [121][122][123] Interestingly, some of the diterpenes substantially inhibited the growth of cultured human umbilical vein endothelial cells, suggesting that they may possess meaningful anti-angiogenic properties. 122 The cell growth inhibitory effects were in some cases accompanied by cell cycle arrest at the G 1 phase and signs of apoptosis.…”

The Ginger Prophecy; A Review of the Underexplored Genus, Hedychium against Cancer

“…The extracts could activate the caspase signalling cascade with enhanced roles of caspase 9, 8 and 3. It successfully downregulated MMP2 and 9 and thus inhibited the migratory capacity of HeLa cells [99] .…”