Antimicrobial effect of different types of honey on Staphylococcus aureus

Honey exhibits antimicrobial activities against a wide range of bacteria in different milieu. This study aims to compare the effects of five types of honey (both imported and local Saudi honey) against Staphylococcus aureus. The five types of honey (Manuka Honey UMF +20, Manuka Honey UMF +16, Active +10 Manuka Honey, Sidr honey and Nigella sativa honey) were evaluated for their bactericidal/bacteriostatic activities against both methicillin resistant and sensitive S. aureus. The inhibitory effect of honey on bacterial growth was evident at concentrations of 20% and 10% (v/v). Manuka Honey showed the best results. Manuka Honey UMF +20 had a bactericidal effect on both methicillin resistant and sensitive S. aureus. However, Sidr and N. sativa honey exerted only a bacteriostatic effect. The efficacy of different types of honey against S. aureus was dependent on the type of honey and the concentration at which it was administered. Manuka Honey had the best bactericidal activity. Future experiments should be conducted to evaluate the effects of honey on bacterial resistance.     

Antimicrobial activities of Saudi honey against Pseudomonas aeruginosa

Five types of imported and local honey were screened for both their bacteriocidal/bacteriostatic activities against both Imipenem resistant and sensitive Pseudomonas aeruginosa in both Brain Heart infusion broth and Mueller–Hinton agar. The results indicated that the effect was concentration and type of honey dependant. All types of honey tested exerted a full inhibition of bacterial growth at the highest concentration tested of 50% at 24 h of contact. The inhibitory effect of honey on bacterial growth was clear with concentrations of 20% and 10% and this effect was most evident in the case of Manuka honey as compared to Nigella sativa honey and Seder honey. Manuka honey UMF +20 showed a bacteriocidal activity on both Imipenem resistant and sensitive P. aeruginosa, while Seder honey and N. sativa honey exerted only a bacteriostatic effect. Manuka honey UMF +10 showed most effect on antimicrobial resistance. Manuka honey UMF +10 had an effect on modulation of Imipenem resistant P. aeruginosa. Conclusion: The results indicated that various types of honey affected the test organisms differently. Modulation of antimicrobial resistance was seen in the case Manuka honey UMF +10.     

A comparison of the sensitivity of wound-infecting species of bacteria to the antibacterial activity of manuka honey and other honey

Both honey and sugar are used with good effect as dressings for wounds and ulcers. The good control of infection is attributed to the high osmolarity, but honey can have additional antibacterial activity because of its content of hydrogen peroxide and unidentified substances from certain floral sources. Manuka honey is known to have a high level of the latter.
Seven major wound-infecting species of bacteria were studied to compare their sensitivity to the non-peroxide antibacterial activity of manuka honey and to a honey in which the antibacterial activity was primarily due to hydrogen peroxide. Honeys with activity in the middle of the normal range were used. A comparison of the median response of the various species of bacteria showed no significant difference between the two types of activity overall, but marked differences between the two types of activity in the rank order of sensitivity of the seven bacterial species. The non-peroxide antibacterial activity of manuka honey at a honey concentration of 1.8% (v/v) completely inhibited the growth of Staphylococcus aureus during incubation for 8 h. The growth of all seven species was completely inhibited by both types of honey at concentrations below 11% (v/v).     

A comparison of the sensitivity of wound-infecting species of bacteria to the antibacterial activity of manuka honey and other honey.

Both honey and sugar are used with good effect as dressings for wounds and ulcers. The good control of infection is attributed to the high osmolarity, but honey can have additional antibacterial activity because of its content of hydrogen peroxide and unidentified substances from certain floral sources. Manuka honey is known to have a high level of the latter. Seven major wound-infecting species of bacteria were studied to compare their sensitivity to the non-peroxide antibacterial activity of manuka honey and to a honey in which the antibacterial activity was primarily due to hydrogen peroxide. Honeys with activity in the middle of the normal range were used. A comparison of the median response of the various species of bacteria showed no significant difference between the two types of activity overall, but marked differences between the two types of activity in the rank order of sensitivity of the seven bacterial species. The non-peroxide antibacterial activity of manuka honey at a honey concentration of 1.8% (v/v) completely inhibited the growth of Staphylococcus aureus during incubation for 8 h. The growth of all seven species was completely inhibited by both types of honey at concentrations below 11% (v/v).     

Intravenous Administration of Manuka Honey Inhibits Tumor Growth and Improves Host Survival When Used in Combination with Chemotherapy in a Melanoma Mouse Model

Manuka honey has been recognized for its anti-bacterial and wound-healing activity but its potential antitumor effect is poorly studied despite the fact that it contains many antioxidant compounds. In this study, we investigated the antiproliferative activity of manuka honey on three different cancer cell lines, murine melanoma (B16.F1) and colorectal carcinoma (CT26) as well as human breast cancer (MCF-7) cells in vitro. The data demonstrate that manuka honey has potent anti-proliferative effect on all three cancer cell lines in a time- and dose-dependent manner, being effective at concentrations as low as 0.6% (w/v). This effect is mediated via the activation of a caspase 9-dependent apoptotic pathway, leading to the induction of caspase 3, reduced Bcl-2 expression, DNA fragmentation and cell death. Combination treatment of cancer cells with manuka and paclitaxel in vitro, however, revealed no evidence of a synergistic action on cancer cell proliferation. Furthermore, we utilized an in vivo syngeneic mouse melanoma model to assess the potential effect of intravenously-administered manuka honey, alone or in combination with paclitaxel, on the growth of established tumors. Our findings indicate that systemic administration of manuka honey was not associated with any alterations in haematological or clinical chemistry values in serum of treated mice, demonstrating its safety profile. Treatment with manuka honey alone resulted in about 33% inhibition of tumor growth, which correlated with histologically observable increase in tumor apoptosis. Although better control of tumor growth was observed in animals treated with paclitaxel alone or in combination with manuka honey (61% inhibition), a dramatic improvement in host survival was seen in the co-treatment group. This highlights a potentially novel role for manuka honey in alleviating chemotherapy-induced toxicity.     

Antibacterial activity of honey and propolis from Apis mellifera and Tetragonisca angustula against Staphylococcus aureus

AIMS: The antibacterial activity against Staphylococcus aureus of honey and propolis produced by Apis mellifera and Tetragonisca angustula was evaluated. Secondary aims included the study of the chemical composition of propolis and honey samples and its relationship with antibacterial activity against S. aureus. METHODS AND RESULTS: The antibacterial activity of honey and propolis was determined by the method of macrodilution. The minimum inhibitory concentration (MICs) of A. mellifera honey ranged from 126.23 to 185.70 mg ml(-1) and of T. angustula from 142.87 to 214.33 mg ml(-1). For propolis, the MIC ranged from 0.36 to 3.65 mg ml(-1) (A. mellifera) and from 0.44 to 2.01 mg ml(-1) (T. angustula). Honey and propolis were evaluated by high-performance liquid chromatography. Some typical compounds of Brazilian propolis were also identified in honey samples. Principal component analysis revealed that the chemical composition of honey and propolis samples was distinct based on the geographical location of the samples. CONCLUSIONS: Propolis samples had higher antibacterial activity against S. aureus when compared with honey. However, both propolis and honey samples had antibacterial against S. aureus. SIGNIFICANCE AND IMPACT OF THE STUDY: These antimicrobial properties would warrant further studies on the clinical applications of propolis and honey against S. aureus.     

Floral markers and biological activity of Saudi honey

The objectives of this research were to identify certain chemical compounds that may be used as fingerprints of Saudi honey and to evaluate their antioxidant and antibacterial activities. Eleven Saudi ‘monofloral’ honey samples were analyzed and evaluated. Non-phenolic compounds, such as 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one, methyl 3-hydroxyhexanaote and 5-hydroxymethyl-2-furancarboxaldehyde were present in different types of tested honey samples. Glyceraldehyde was only detected in five of the honey samples tested. The most promising result was the detection of an alkaloid (by using GC–MS) in only two types of Saudi honey samples. This alkaloid may be of great importance and has the potential to be used as a fingerprint marker for the botanical sources of the various honey samples tested. This alkaloid was present in Toran and Saha. The detected compound is 2-amino-4-hydroxypteridine-6-carboxylic acid, which may originate from the degradation of folic acid as identified by previous studies. These findings can be used as a gateway to obtain a fingerprint for these two types of honey samples and can potentially be used to track any impurities in honey sold on the market. All of the tested honey samples showed antioxidant and antibacterial activities. The highly effective activity was in Toran honey against Staphylococcus aureus and Methicillin resistant Staphylococcus aureus (MRSA). Shafalah honey was effective against MRSA and Acinetobacter baumannii which showed bactericidal effects at concentrations 70–100%. This study also examined the antioxidant activity of honey samples using the DPPH assay. DPPH values of tested honey samples varied between 53.93?±?0.21%, as the highest value and 5.89?±?0.125%, as the lowest value. Significant correlations between the antibacterial and the antioxidant activities of the tested honey samples were noticed. The corresponding total phenolic contents (TPC) values supported the fact that phenolic compounds enhanced the antibacterial activity. The study revealed that some of the locally produced honey samples, specifically Zaitoon, Shaflah, Saha, Rabea Aja and Bareq contained the monosaccharides called glyceraldehydes which was the precursor to produce methylglyoxal (MGO) compound, which has antibacterial effects as documented in several previous studies. There was no clear relationship between these activities and the sum total of phenolic compounds present in Saudi honey.     

Antioxidant and antibacterial capacity of stingless bee honey from Borneo (Sarawak)

Stingless honey bees form a large group of bees that lack of a sting and are found among Meliponinae species indigenous to various tropical and subtropical regions. They are able to produce “stingless bee honey” that contains divergent categories of phenolic and flavonoid compounds and have been associated with antioxidant and antibacterial activity. This study examines the physicochemical properties, antioxidant-activity and anti-microbial activity of stingless bee honey from Malaysia that was produced by Geniotrigona thoracica, Heterotrigona itama and Heterotrigona erythrogastra. The results show that G. thoracica honey has the highest concentration of the total phenolic context (99.04?±?5.14?mg/ml) and the greatest reducing power (19.05?±?0.79%), while flavonoids (17.67?±?0.75?mg/ml), reducing power (18.10?±?0.35%), DPPH (47.40?±?3.18%) and FRAP (50.66?±?5.77?mM of Fe²⁺/100?g) of H. itama honey is significantly higher than those of the other honeys. In addition, G. thoracica honey has the highest antibacterial activity against Staphylococcus xylosus (2.10?±?0.10?cm), which is Gram-positive bacterium, and against Pseudomonas aeruginosa (1.60?±?0.10?cm) and Vibrio parahaemolyticus (2.03?±?0.06?cm), which are Gram-negative bacteria. These results suggest that stingless bee honeys possess useful amounts of phenolic and flavonoid compounds that are able to act as natural anti-oxidants and also have significant anti-microbial activity.     

Antibacterial components of honey

The antibacterial activity of honey has been known since the 19th century. Recently, the potent activity of honey against antibiotic-resistant bacteria has further increased the interest for application of honey, but incomplete knowledge of the antibacterial activity is a major obstacle for clinical applicability. The high sugar concentration, hydrogen peroxide, and the low pH are well-known antibacterial factors in honey and more recently, methylglyoxal and the antimicrobial peptide bee defensin-1 were identified as important antibacterial compounds in honey. The antibacterial activity of honey is highly complex due to the involvement of multiple compounds and due to the large variation in the concentrations of these compounds among honeys. The current review will elaborate on the antibacterial compounds in honey. We discuss the activity of the individual compounds, their contribution to the complex antibacterial activity of honey, a novel approach to identify additional honey antibacterial compounds, and the implications of the novel developments for standardization of honey for medical applications.     

Harvested locations influence the total phenolic content,antioxidant levels,cytotoxic, and anti-inflammatory activities of stingless bee honey

Kelulut honey (KH) is a natural product-derived food produced by stingless bees of Trigona or Meliponine species. Several studies have shown that the geographical origin of honey significantly affects its pharmacological properties. Thus, this study aims to characterise the pharmacological properties of KH harvested from different geographical locations. The total phenolic content (TPC), antioxidant levels, cytotoxic, and anti-inflammatory activities of pure KH harvested from three different locations (Sarawak, Pahang and Selangor) were compared. Among the samples, KH harvested from Selangor exhibited the highest TPC, antioxidant levels, and cytotoxic activity against MDA-MB-231 and MCF-7 cells, followed by KH harvested from Sarawak and Pahang. The IC₅₀ of MCF-7 cells treated with KH harvested from Selangor was at least 2-fold lower than the IC₅₀ of MDA-MB-231 cells, suggesting that KH is more cytotoxic to oestrogen receptor (ER)- and progesterone receptor (PR)-positive (MCF-7) compared to triple-negative (MDA-MB-231) breast cancer cells. Two non-cytotoxic concentrations (1% and 0.5%; v/v) were selected for the anti-inflammatory assay using lipopolysaccharide (LPS)-induced RAW 264.7 cells. KH harvested from Selangor and Pahang (at a concentration of 1%; v/v) significantly inhibited nitric oxide (NO) production in LPS-induced RAW 264.7 cells compared to control cells. These findings provide evidence that the geographical origin of KH may indeed influence its pharmacological properties. Our data suggest that KH harvested from Selangor has a better quality compared to KH harvested from Pahang and Sarawak based on its high TPC, antioxidant levels and anti-inflammatory activity. Furthermore, it exhibits in vitro anticancer potential in breast cancer cell lines.     

Antimicrobial,immunomodulatory and cytotoxic activities of green synthesized nanoparticles from Acacia honey and Calotropis procera

Calotropis procera and Somra (Acacia) honey are used in traditional medicine. The benefits of mixing 20% Somra honey and C. procera leaf water extract (CPLWExt) were aimed to be studied. Honey/CPLWExt were utilized to produce silver nanoparticles (AgNPs) separately. AgNPs were characterized via UV/Vis and electron microscope scanning. Bio-molecules in CPLWExt/honey were investigated utilizing FT-IR spectroscopy. Biological activities of CPLWExt and honey were tested. The outcomes showed that CPLWExt and honey have numerous functional groups and could produce AgNPs. CPLWExt, CPLWExt + AgNPs, honey and honey + AgNPs hindered the growth of rat splenocytes, while CPLWExt + honey invigorated it. Antimicrobial power was found in CPLWExt and honey, which increased in the presence of AgNPs. Honey/honey + AgNPs suppressed the proliferation of HeLa and HepG2 cells. In conclusion, honey/CPLWExt could produce AgNPs and showed immunomodulatory and antibacterial power. Somra honey/honey + AgNPs have anticancer power. Somra honey + CPLWExt reflected a good immunostimulatory powers that can be nominated as an immunostimulant.     

The in vitro effect of manuka honeys on growth and adherence of oral bacteria

Honey has been used since ancient times and more recently, for the healing of wounds and against infectious diseases. The aim of our study was to investigate the effect of two manuka honeys showing different potencies of their antibacterial activity, on potentially pathogenic oral bacteria. The antimicrobial activity was examined by determining the MIC and MBC using the macro dilution broth technique. The effect on the adherence was tested on growing cells of Streptococcus mutans on a glass surface and on a multi-species biofilm grown on saliva-coated hydroxyapatite discs. As expected, the antibacterial activity of manuka 1 (with higher potency of antibacterial activity) was the most important. The two tested honeys weakly inhibited the adherence of S.mutans cells to a glass surface at sub-MIC concentration. Manuka 1 showed a total inhibition of multi-species biofilm at the concentration of 200 μg/ml manuka 2 inhibited biofilm formation weakly at the concentration of 200 μg/ml but firmly at the concentration of 500 μg/ml. Our findings suggest that manuka honeys might be able to reduce oral pathogens within dental plaque. These two honeys appear to be able to control dental biofilm deposit.     

Isolation by HPLC and characterisation of the bioactive fraction of New Zealand manuka (Leptospermum scoparium) honey

Using HPLC a fraction of New Zealand manuka honey has been isolated, which gives rise to the non-peroxide antibacterial activity. This fraction proved to be methylglyoxal, a highly reactive precursor in the formation of advanced glycation endproducts (AGEs). Methylglyoxal concentrations in 49 manuka and 34 non-manuka honey samples were determined using a direct detection method and compared with values obtained using standard o-phenylenediamine derivatisation. Concentrations obtained using both the methods were similar and varied from 38 to 828 mg/kg.     

Design,synthesis and biological evaluation of novel quinazoline derivatives as potential anti-cancer agents

Twenty-two quinazoline derivatives have been synthesised and examined for their anti-tumour activity against three tumour cell lines, namely human breast cancer cell line (MCF-7), human cervical cancer cell line (HeLa) and human hepatoma cell line (HepG2). Twelve of the tested compounds have shown promising anti-tumour activity with an IC₅₀ range of 5.0–9.7 µg/mL. Regarding the spectrum of activity, five compounds exhibited interesting anti-proliferative properties against the three tested cell lines comparable to the reference drug (dasatinib).     

The origin of methylglyoxal in New Zealand manuka (Leptospermum scoparium) honey

Methylglyoxal in New Zealand manuka honey has been shown to originate from dihydroxyacetone, which is present in the nectar of manuka flowers in varying amounts. Manuka honey, which was freshly produced by bees, contained low levels of methylglyoxal and high levels of dihydroxyacetone. Storage of these honeys at 37 °C led to a decrease in the dihydroxyacetone content and a related increase in methylglyoxal. Addition of dihydroxyacetone to clover honey followed by incubation resulted in methylglyoxal levels similar to those found in manuka honey. Nectar washed from manuka flowers contained high levels of dihydroxyacetone and no detectable methylglyoxal.     

Anti-tumor activity evaluation of novel chrysin–organogermanium(IV) complex in MCF-7 cells

Chrysin (5,7-dihydroxylflavone, Chry) is a natural product extracted from plants, honey, and propolis. In this work, a novel chrysin–organogermanium(IV) complex (Chry–Ge) with enhanced anticancer activities was synthesized, and its potential anticancer effects against cancer cells were measured using various methods. MTT results showed that Chry–Ge had significant inhibition effects on the proliferation of MCF-7, HepG2 and Colo205 human cancer cell lines in a dose-dependent manner while had little cytotoxic effects on MCF-10A human normal cells (MCF-10A cells) with the same treatment of Chry–Ge. These results suggested that Chry–Ge possessed enhanced anticancer effects and high selectivity between cancer cells and normal cells. The immuno-staining results showed that the nuclei of MCF-7 cells represented a total fragmented morphology and a disorganized cytoskeletal network in MCF-7 cells after Chry–Ge treatment. Besides, atomic force microscopy (AFM) was applied to detect the changes of ultrastructural and biomechanical properties of MCF-7 cellular membrane induced by Chry–Ge. The AFM data indicated that Chry–Ge treatment directly caused the decrease of cell rigidity and adhesion force of MCF-7 cells, suggesting that membrane toxicity might be one of the targets for Chry–Ge in MCF-7 cells. Moreover, the fluorescence-based flow cytometric analysis demonstrated that Chry–Ge could induce apoptosis in MCF-7 cells in ROS-dependent mitochondrial pathway. All results collectively showed that Chry–Ge could be as a promising anticancer drug for cancer therapy.     

The sensitivity to honey of Gram-positive cocci of clinical significance isolated from wounds

AIMS: To determine the sensitivity to honey of Gram-positive cocci of clinical significance in wounds and demonstrate that inhibition is not exclusively due to osmotic effects. METHODS AND RESULTS: Eighteen strains of methicillin-resistant Staphylococcus aureus and seven strains of vancomycin-sensitive enterococci were isolated from infected wounds and 20 strains of vancomycin-resistant enterococci were isolated from hospital environmental surfaces. Using an agar incorporation technique to determine the minimum inhibitory concentration (MIC), their sensitivity to two natural honeys of median levels of antibacterial activity was established and compared with an artificial honey solution. For all of the strains tested, the MIC values against manuka and pasture honey were below 10% (v/v), but concentrations of artificial honey at least three times higher were required to achieve equivalent inhibition in vitro. Comparison of the MIC values of antibiotic-sensitive strains with their respective antibiotic-resistant strains demonstrated no marked differences in their susceptibilities to honey. CONCLUSIONS: The inhibition of bacteria by honey is not exclusively due to osmolarity. For the Gram-positive cocci tested, antibiotic-sensitive and -resistant strains showed similar sensitivity to honey. SIGNIFICANCE AND IMPACT OF THE STUDY: A possible role for honey in the treatment of wounds colonized by antibiotic-resistant bacteria is indicated.     

Synthesis and bioevaluation study of novel N-methylpicolinamide and thienopyrimidine derivatives as selectivity c-Met kinase inhibitors

Four series of N-methylpicolinamide moiety and thienopyrimidine moiety bearing pyridazinone were designed and synthesized and evaluated for the IC₅₀ values against three cancer cell lines (A549, HepG2 and MCF-7) and some selected compounds were further evaluated for the activity against c-Met, Flt-3, VEGFR-2, c-Kit and EGFR kinases. Three compounds (35, 39 and 43) showed more active than positive control Foretinib against A549, HepG2 and MCF-7 cell lines. The most promising compound 43 showed superior activity against A549, HepG2 and MCF-7, with the IC₅₀ values of 0.58?±?0.15?µM, 0.47?±?0.06?µM and 0.74?±?0.12?µM, which were 3.73–5.39-fold more activity than Foretinib, respectively. The experiments of enzyme-based showed that 43 restrain the c-Met selectively, with the IC₅₀ values of 16?nM, which showed equal activity to Foretinib (14?nM) and better than the compound 5 (90?nM). Moreover, AO and Annexin V/PI staining and docking studies were carried out.     

The antibacterial activities of honey

Honey is a powerful antimicrobial agent with a wide range of effects. Various components contribute to the antibacterial efficacy of honey: the sugar content; polyphenol compounds; hydrogen peroxide; 1,2-dicarbonyl compounds; and bee defensin-1. All of these elements are present at different concentrations depending on the source of nectar, bee type, and storage. These components work synergistically, allowing honey to be potent against a variety of microorganisms including multidrug resistant bacteria and modulate their resistance to antimicrobial agents. The effectiveness and potency of honey against microorganisms depends on the type of honey produced, which is contingent on its botanical origin, the health of the bee, its origin, and processing method. The application of antibiotics with honey yielded better antimicrobial potential and synergistic effects were noted against biofilms. In medicine, honey has been used in the treatment of surface wounds, burns, and inflammation, and has a synergistic effect when applied with antibiotics. Tissue repair is enhanced by the low pH of honey (3.5–4): causing a reduction in protease activity on the wound site, elevating oxygen release from hemoglobin and stimulating fibroblast and macrophage activity. Furthermore, H₂O₂ has antiseptic effects, and it disinfects the wound site and stimulates production of vascular endothelial growth factor. The use of honey will clean wounds or burn areas from free radicals and reduces scarring and contractures. The anti-inflammatory and antibacterial potential of honey will keep the injured area moist and as such prevents it from deterioration and fibrosis. Honey can promote fast healing and reduce scarring and is very convenient for plastic surgery. Skin maceration is protected by honey due to its high osmolarity and because it keeps the injury moist. In non-infected areas, honey still reduced pain and inflammation. In general, the use of honey in medical settings has reduced economic loss and provided proven economic benefits by lowering direct costs in comparison to conventional treatments and by using less antibiotics, faster healing and less hospitalization stay. This review is intended to provide an overview of the antibacterial activities of honey and its applications.     

In vitro cytotoxic potential of Solanum nigrum against human cancer cell lines

Plants have natural products which use to possess antiproliferative potential against many cancers. In the present study, six isolated fractions (ethyl acetate, petroleum ether, chloroform, n-butanol, ethanol and aqueous) from Solanum nigrum were evaluated for their cytotoxic effect on different cell lines. Hepatic carcinoma cell line (HepG2), cervical cancer cell line (HeLa) and baby hamster kidney (BHK) used as normal non-cancerous cells were evaluated for cytotoxicity against isolated fractions. Cell viability assay was performed to evaluate the cytotoxicity of all fractions on different cell lines followed by the lactate dehydrogenase and vascular endothelial growth factor assays of most active fraction among all screened for cytotoxic analysis. HPLC analysis of most active fractions against cytotoxicity was performed to check the biological activity of compounds. Results displayed the potent cytotoxic activity of ethyl acetate fraction of S. nigrum against HepG2 cells with IC₅₀ value of 7.89 μg/ml. Other fractions exhibited potent anticancer activity against HepG2 cells followed by HeLa cells. Fractions in our study showed no cytotoxicity in BHK cells. Cytotoxic activity observed in our current study exposed high antiproliferative potential and activity of ethyl acetate fraction against HepG2 cells. The results demonstrated that S. nigrum fractions exhibited anticancer activity against hepatic and cervical cancer cell lines with non-toxic effect in normal cells. These results reveal significant potential of S. nigrum for the therapeutic of cancers across the globe in future.