A monoterpene, unique component of thyme honeys, induces apoptosis in prostate cancer cells via inhibition of NF-[kappa]B activity and IL-6 secretion.
Abstract We have previously demonstrated that Greek thyme honey inhibits significantly the cell viability of human prostate cancer cells. Herein, 15 thyme honey samples from several regions of Greece were submitted to phytochemical analysis for the isolation, identification and determination (through modern spectral means) of the unique thyme honey monoterpene, the compound trihydroxy ketone E-4-(1,2,4-trihydroxy-2,6,6- trimethylcyclohexyl)-but-3-en-2-one.
We investigated the anti-growth and apoptotic effects of the trihydroxy ketone on PC-3 human androgen independent prostate cancer cells using MTT assay and Annexin V-FITC respectively. The molecular pathways involved to such effects were further examined by evaluating its ability to inhibit (a) the NF-[kappa]B phosphorylation (S536), (b)JNK and Akt phosphorylation (Thrl 83/Tyrl 85 and S473 respectively) and (c) IL-6 production, using ELISA method. The anti-microbial effects of the trihydroxy ketone against a panel of nine pathogenic bacteria and three fungi were also assessed.
The trihydroxy ketone exerted significant apoptotic activity in PC-3 prostate cancer cells at 100 [micro]M, while it inhibited NF-[kappa]B phosphorylation and IL-6 secretion at a concentration range [10.sup.-6]-[10.sup.-4] M. Akt and JNK signaling were not found to participate in this process. The trihydroxy ketone exerted significant anti-microbial profile against many human pathogenic bacteria and fungi (MIC values ranged from 0.04 to 0.57 mg/ml). Conclusively, the Greek thyme honey-derived monoterpene exerted significant apoptotic activity in PC-3 cells, mediated, at least in part, through reduction of NF-[kappa]B activity and IL-6 secretion and may play a key role in the anti-growth effect of thyme honey on prostate cancer cells.
"Coffee plus Honey" versus "topical steroid" in the treatment of Chemotherapy-induced Oral mucositis: a randomised controlled trial Mohammad Ali Raeessi, Neda Raeessi, Yunes Panahi, Homa Gharaie, Seyyed Masoud Davoudi, Alireza Saadat, Ali Akbar Karimi Zarchi, Fereshteh Raeessi, Seyyed Mostafa Ahmadi and Hamidreza Jalallian
Abstract Background Oral mucositis is one of the common complications of cancer chemotherapy and about 40% of the patients who take chemotherapy protocols, experience this irritating problem. The purpose of this study was to draw comparison between the therapeutic effects of our treatment modalities (topical steroid, honey, honey plus coffee) in patients suffering from oral mucositis.
Methods This was a double blinded randomised clinical trial of a total of 75 eligible adult participants which they randomly fell into three treatment groups. For all the participants a syrup-like solution was prepared. Each 600 grams of the product consisted of "20 eight-mg Betamethasone solution ampoules" in the Steroid (S) group, "300 grams of honey plus 20 grams of instant coffee" in the Honey plus Coffee (HC) group, and "300 grams of honey" for the Honey (H) group. The participants were told to sip 10 ml of the prescribed product, and then swallow it every three hours for one week. Severity of lesions was clinically evaluated before the treatment and also one week after the initiation of the intervention. This study adhered to the principles of the Declaration of Helsinki and guidelines of Good Clinical Practice.
Results This study showed that all three treatment regimens reduce the severity of lesions. The best reduction in severity was achieved in HC group. H group and S group took the second and third places. In other words, honey plus coffee regimen was the most effective modality for the treatment of oral mucositis.
Conclusion Oral mucositis can be successfully treated by a combination of honey and coffee as an alternative medicine in a short time. Further investigations are warranted in this field
Antiproliferative effect of Tualang honey on oral squamous cell carcinoma and osteosarcoma cell lines
Abdulmlik A Ghashm1, Nor H Othman2, Mohammed N Khattak2, Noorliza M Ismail1, Rajan Saini1*
Cancer of the oral cavity is eleventh most common malignancy worldwide  while in the Indian subcontinent and regions of Southeast Asia, it is the predominant malignancy accounting for up to 40% of all the cancers . This high incidence of oral cancer is primarily attributable to the habit of tobacco, betel quid chewing and alcohol consumption . Oral squamous cell carcinomas (OSCC) are the most common type of oral cancers. Similarly, Human Osteosarcomas (HOS) that arise from the jaw, account for 2.1% of all malignant oral and maxillofacial tumours . The treatment of these types of oral cancers includes surgery and/or radiotherapy, which are often associated with loss of function, disfigurement and reduced quality of life . Recently, advances in chemotherapeutic agents for the treatment of OSCCs have been highlighted but the survival rate of patients has not improved significantly. The development of novel therapeutic agents targeting the malignant behaviour of these cancers is important to improve the prognosis of treatment . The study of molecular mechanisms of chemotherapeutic agents and the combination of chemotherapeutic agents that induce synergistic anticancer activity are necessary to improve clinical outcomes .
Many researchers have studied the anticancer activities of drugs or herbal extracts on OSCC cell lines. These include Tamoxifen in combination with Cisplatin , 5-Fluorouracil , Cordycepin , Scutellaria baicalensis , Quercetin  Artemisinin  and others. Similarily, Ginsenoside Rg1, Cinnamic acid, and Tanshinone IIA , Diosgenin, Venenum Bufonis and Oxgall powder have been shown to have antiproliferative effect on HOS cell lines. Honey is a food product which is collected from various plants and processed by honey bees (Apis mellifera). Honey has been used as traditional medicine for centuries in different cultures, not only for its nutritional value but also its healing properties. Recently, honey has been tested and approved scientifically for its functional and biological properties like anti-oxidant, anti-inflammatory, anti-bacterial, anti-viral, anti-ulcerous activities, anti-lipid and anti-cancer properties [16-23]. These activities are mainly attributed to the phenolic compounds such as flavonoids having antioxidant properties and radical scavenging activities seen among all types of honeys in different proportions, depending on the geographical areas, source of honeybee food and climate [24-26]. Honey has also been used in palliative care of various cancers like in radiation-induced mucositis, radiotherapy and chemotherapy induced skin reactions and wounds . It has also been shown to produce antiproliferative effects in bladder cancer , colon cancer , mammary carcinoma and fibrosarcoma . However, till date no study has been found to show antiproliferative effects of honey on oral cancers. Malaysian Tualang honey is collected from the honey combs of Asian rock bees (Apis dorsata), which build their hives high up in the Tualang tree (Koompassia excelsa). Tualang honey is used commonly as a medicinal product  and as a food in Malaysia. Recently, antibacterial properties of this honey have been studied and compared with other honeys [30,31]. However, its antiproliferative properties are yet to be studied. The purpose of the current study was to investigate the antiproliferative activity of Malaysian Tualang honey on OSCC and HOS cell lines.
Several concentrations of Tualang honey (1% - 20%) were applied on OSCC and HOS cell lines for 3, 6, 12, 24, 48 and 72 hours. Morphological characteristics were observed under light and fluorescent microscope. Cell viability was assessed using MTT assay and the optical density for absorbance values in each experiment was measured at 570 nm by an ELISA reader. Detection of cellular apoptosis was done using the Annexin V-FITC Apoptosis Detection Kit.
Morphological appearance showed apoptotic cellular changes like becoming rounded, reduction in cell number, blebbed membrane and apoptotic nuclear changes like nuclear shrinkage, chromatin condensation and fragmented nucleus on OSCC and HOS cell lines. Cell viability assay showed a time and dose-dependent inhibitory effect of honey on both cell lines. The 50% inhibitory concentration (IC50) for OSCC and HOS cell lines was found to be 4% and 3.5% respectively. The maximum inhibition of cell growth of ≥80% was obtained at 15% for both cell lines. Early apoptosis was evident by flow cytometry where percentage of early apoptotic cells increased in dose and time dependent manner.
Tualang honey showed antiproliferative effect on OSCC and HOS cell lines by inducing early apoptosis.