gingerol and Uterine-Cervical-Neoplasms

Cervical cancer is one of the most common and important gynecological cancers, which has a global concern with an increasing number of patients and mortality rates. Today, most women in the world who suffer from cervical cancer are developing advanced stages of the disease. Smoking and even exposure to secondhand smoke, infections caused by the human papillomavirus, immune system dysfunction and high-risk individual-social behaviors are among the most important predisposing factors for this type of cancer. In addition, papilloma virus infection plays a more prominent role in cervical cancer. Surgery, chemotherapy or radical hysterectomy, and radiotherapy are effective treatments for this condition, the side effects of these methods endanger a person's quality of life and cause other problems in other parts of the body. Studies show that herbal medicines, including taxol, camptothecin and combretastatins, have been shown to be effective in treating cervical cancer. Ginger (Zingiber officinale, Zingiberaceae) is one of the plants with valuable compounds such as gingerols, paradols and shogoals, which is a rich source of antioxidants, anti-cancer and anti-inflammatory agents. Numerous studies have reported the therapeutic effects of this plant through various pathways in cervical cancer. In this article, we look at the signaling mechanisms and pathways in which ginger is used to treat cervical cancer.

Topics: Catechols; Fatty Alcohols; Female; Humans; Uterine Cervical Neoplasms; Zingiber officinale

Topics: Antineoplastic Agents; Apoptosis; Catechols; Cell Cycle Checkpoints; Cell Proliferation; Cyclin E; Fatty Alcohols; Female; HeLa Cells; Humans; Phosphatidylinositol 3-Kinases; Plant Extracts; Tandem Mass Spectrometry; Uterine Cervical Neoplasms; Zingiber officinale

The anti-cancerous activity of 6-gingerol extracted from Tongling White Ginger was investigated. 6-Gingerol inhibited the growth of HeLa cells with IC50 (96.32 μM) and IC80 (133.01 μM) and led to morphological changes, induced the cell cycle arrest in G0/G1-phase and ultimately resulted into apoptosis. Among cell cycle-related genes and proteins, the expression of cyclin (A, D1, E1) reduced, while of CDK-1, p21 and p27 showed slight decrease, except cyclin B1 and E1 (protein). Western blotting reported the induction of apoptosis with an increased Bax/Bcl-2 ratio, release of cytochrome c, cleavage of caspase-3, -8, -9 and PRPP in treated cells. 6-Gingerol activated AMPK, but inhibited PI3K/AKT phosphorylation with reduced P70S6K expression and also suppressed the mTOR phosphorylation. 6-Gingerol with 5-FU and Ptx resulted in 83.2% and 52% inhibition respectively, this synergy have stimulated apoptosis proteins more efficiently as compared to 6-Gingerol alone (10.75%) under in vitro conditions.

Topics: Adenocarcinoma; Antineoplastic Agents; Apoptosis; Caspase 3; Catechols; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Drug Evaluation, Preclinical; Drug Synergism; Fatty Alcohols; Female; Fluorouracil; Humans; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Uterine Cervical Neoplasms; Zingiber officinale

6-Gingerol, a potent nutraceutical, has been shown to have antitumor activity in different tumors, although its mechanism of action is not well understood. In this study, we evaluated antitumor activities of 6-gingerol on human oral (SCC4, KB) and cervical cancer (HeLa) cell lines with or without wortmannin, rapamycin, and cisplatin. Tumor cell proliferation was observed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium, inner salt assay, cell cycle analysis by propidium iodide labeling and flow cytometry, apoptosis by Annexin-V binding assay, and caspase activity by chemiluminescence assay. 6-Gingerol showed dose-dependent cytotoxicity in all three cell lines. Combinations of 6-gingerol with wortmannin and cisplatin showed additive effects, while with rapamycin, it showed 50% cytotoxicity that was equivalent to IC50 of 6-gingerol alone. Treatment with 6-gingerol resulted in G2-phase arrest in KB and HeLa cells and S-phase arrest in SCC4 cells. 6-Gingerol, wortmannin, and rapamycin treatment showed almost two-fold higher expression of caspase 3 in all cell lines. The results imply that 6-gingerol either alone or in combination with PI-3 K inhibitor and cisplatin may provide better therapeutic effects in oral and cervical carcinoma. Thus, 6-gingerol appears to be a safe and potent chemotherapeutic/chemopreventive compound acting through cell cycle arrest and induction of apoptosis in human oral and cervical tumor cells.

Topics: Androstadienes; Apoptosis; Caspase 3; Catechols; Cell Cycle Checkpoints; Cell Division; Cell Line, Tumor; Cell Proliferation; Cisplatin; Fatty Alcohols; Female; HeLa Cells; Humans; Mouth Neoplasms; Sirolimus; Uterine Cervical Neoplasms; Wortmannin

Human papilloma virus (HPV) expressing E6 and E7 oncoproteins, is known to inactivate the tumor suppressor p53 through proteasomal degradation in cervical cancers. Therefore, use of small molecules for inhibition of proteasome function and induction of p53 reactivation is a promising strategy for induction of apoptosis in cervical cancer cells. The polyphenolic alkanone, 6-Gingerol (6G), present in the pungent extracts of ginger (Zingiber officinale Roscoe) has shown potent anti-tumorigenic and pro-apoptotic activities against a variety of cancers. In this study we explored the molecular mechanism of action of 6G in human cervical cancer cells in vitro and in vivo. 6G potently inhibited proliferation of the HPV positive cervical cancer cells. 6G was found to: (i) inhibit the chymotrypsin activity of proteasomes, (ii) induce reactivation of p53, (iii) increase levels of p21, (iv) induce DNA damage and G2/M cell cycle arrest, (v) alter expression levels of p53-associated apoptotic markers like, cleaved caspase-3 and PARP, and (vi) potentiate the cytotoxicity of cisplatin. 6G treatment induced significant reduction of tumor volume, tumor weight, proteasome inhibition and p53 accumulation in HeLa xenograft tumor cells in vivo. The 6G treatment was devoid of toxic effects as it did not affect body weights, hematological and osteogenic parameters. Taken together, our data underscores the therapeutic and chemosensitizing effects of 6G in the management and treatment of cervical cancer.

Topics: Animals; Antineoplastic Agents; Blotting, Western; Catechols; Cell Proliferation; Fatty Alcohols; Female; Flow Cytometry; HeLa Cells; Humans; Male; Mice; Mice, Nude; Microscopy, Confocal; Molecular Docking Simulation; Papillomavirus Infections; Proteasome Endopeptidase Complex; Real-Time Polymerase Chain Reaction; RNA, Small Interfering; Transfection; Tumor Suppressor Protein p53; Uterine Cervical Neoplasms; Xenograft Model Antitumor Assays

Benjakul [BEN], a Thai Traditional medicine preparation, is composed of five plants: Piper chaba fruit [PC], Piper sarmentosum root [PS], Piper interruptum stem [PI], Plumbago indica root [PL] and Zingiber officinale rhizome [ZO]. From selective interviews of folk doctors in Southern Thailand, it was found that Benjakul has been used for cancer patients.. To investigate cytotoxicity activity of Benjakul preparation [BEN] and its ingredients against three human cancer cell lines, large lung carcinoma cell line (COR-L23), cervical cancer cell line (Hela) liver cancer cell line (HepG2) as compared with normal lungfibroblast cell (MRC-5) by using SRB assay.. The extraction as imitated the method used by folk doctors was done by maceration in ethanol and boiling in water Bioassay guided isolation was used isolated cytotoxic compound.. The ethanolic extracts of PL, ZO, PC, PS, BEN and PS showed specific activity against lung cancer cell (IC50 = 3.4, 7.9, 15.8, 18.4, 19.8 and 32.91 microg/ml) but all the water extracts had no cytotoxic activity. Three active ingredients [6-gingerol, plumbagin and piperine as 0.54, 4.18 and 7.48% w/w yield of crude extract respectively] were isolated from the ethanolic extract of BEN and they also showed cytotoxic activity with plumbagin showing the highest cytotoxic activity against COR-L23, HepG2, Hela and MRC-5 (IC50 = 2.55, 2.61, 4.16 and 11.54 microM respectively).. These data results may support the Thai traditional doctors who are using Benjakul to treat cancer patients and three of its constituents (6-gingerol, plumbagin and piperine) are suggested to be used as biomarkers for standardization of this preparation.

Topics: Alkaloids; Benzodioxoles; Catechols; Cell Line, Tumor; Fatty Alcohols; Female; Humans; Liver Neoplasms; Lung Neoplasms; Medicine, East Asian Traditional; Naphthoquinones; Phytotherapy; Piper; Piperidines; Plant Extracts; Plants, Medicinal; Plumbaginaceae; Polyunsaturated Alkamides; Thailand; Uterine Cervical Neoplasms; Zingiber officinale