Eight Annual AACR International Conference on Frontiers in Cancer Prevention Research Houston, Texas, U.S.A. 06-09 Disember 2009

Eptdemrologrcal studres have demonstrated a posrtNe cooeldtion between consumption of vE'(jeldbles, frurts and bevt:r ages with reduced mk of canre. It 1s esumated there are around 8,100 plant speer~ 'in the Mal.~ysian rain forests. wrth 1 0% of them reported to have some medicinal value. HOWE'\Ier, to date m Malaysta, not much investigdtion has been donP on chE>mopreventiw actrvitrP.S on cancer although Malaysran plants are an exclusrve !.Ottrce of effe<trve themopreventrve agents and therefore. thrs batkground leads to the premrse that our local plants such as Streblus asper could have greater potentral for the chemoprevention a<tJVrlles. Streblus asper rs well known as an expensrve bon~11 plant whrch rs rndrgenous to tropccal countnes such as Malaysia. Thailand. Srr Lanka and lndra It rs used tradiuonally rn leprosy. pries. drarrhea. dysentery. elephantrasis and cancer tt finds place in AyurvediC Pharmacopoeia of India and also been descrrbed m some monographs, but none have reported rts activity as chelllOpfeventive ~ts and the underlyrng mear In the present study, we try ro identify its brologrcal properues and the cytotoKrdty efle<t on normallrver and kidney cells. Us1ng the osteosarcoma cells as our 1n vrtlo model, the ICSO of Streblus asper root eXtract was deterrnrned and observed rts efle<t on the osteosarcoma cells morphology that changes w1thrn trme. the anu prolifer atrve pattern and live-death analysis under confocal mrcroscope analysrs. The results showed thdt the root extracts drd not contarned any heavy metals compound such as mercury and cadmium and With less arsenrc (0 02 ppm) clnd plumbum (0.07 ppm) and ~ing non·<)'totoxrc effect on vero cells (normal krdney cells} and WRL·68 (E'tls (normal liver cells) Our HPLC profiling analysrs also r!'Vealed antroxidants compounds exrst rn the Streblus asper root extracts such as caffeic acid which has been shown to dCI as a carcrnogenrc rnhibrtOI Although the low·fevef of antr-oxrdants been found from the extracts but rt strll can rnhrbrt thl' growth of the osteosarcoma cells wtuch also exerl dpoptosis features l1ke cell sh11nkage (atrophy) and vocalizatron rn trme and dose-dependent manner The plant extracts IC50 doses was Jt 0.05% of root extracts and rt also demonstrated the ant•·prolifLoratrve effe<t by suppressed the cells growth as early as 12 hours of treatment and marked cell death t1il day 6 On live'ileath analys~s under confocal mrcroscope usrng Calcern and Ethrdrum starnrng confrrmed that Streblus asper root extract exer1 cell death to osteosarsoma cells. This study IS Just a prelimrnary study as to identrfy rts pharmucologrcal propertres on c,:~~crnogenesrs and further rnvestrga110n rs strll on-gorng to develop rt as the chemopreventrve agent espec:ialty to determrne the srgnaling pathway involve

New strategy in development of cancer chemopreventive agent using Malaysia Plant

Cancer had become worldwide problem that efforts in prevention and treatment of cancer had rapidly grew in any research institute. Meanwhile, epidemiological studies have demonstrated a positive correlation between consumption of vegetables, fruits and beverages with reduced risk of cancer. It is estimated there are around 8,100 plant species in the Malaysia rain forests, with 10% of them reported to have some medicinal value. However, to date not much investigation has been done on chemopreventive activities on cancer. Therefore, we had studied the chemopreventive activity using various type of local plants such as Christia sp, Nephelium lappaceuem, Cocos nucifera and many more others which we going to present here. But, to combat with this miserable disease, we still need new strategies to overcome the problem and we also utilized the waste product from our tropical fruits and Paddy waste which might have beneficial effect towards cancer chemoprevention activities. We also going to present our strategy in developing mouthwash product to prevent oral cancer using bonsai plant, Streblus asper with demonstrable efficacy against defined molecular target on cancer cell line as well as in animal models. It is clearly shown that S. asper root extracts that have the anti-oxidant characteristic with analgesic properties via Inositol, not only kill oral-microbes but interestingly also inhibit the growth of osteosarcoma cells, tongue carcinoma cells and cervical cancer cells. The inhibition effect was through the induction of apoptosis signaling pathway. This mouthwash product also is non-toxic for the liver, kidney and skin fibroblast cells and no heavy metals were found. Currently, we now focused the use of the same product on cervical cancer and might develop it as a ladies hygiene product which act as chemopreventive agent. Futhermore S.asper also can suppressed the proliferative activity of the epithelium cells in Benign Prostate Hyperplasia animal model. Lets combat the cancer disease using new strategies

Anticancer activity of grassy Hystrix brachyura bezoar and its mechanisms of action: An in vitro and in vivo based study

Porcupine bezoar (PB) is a calcified undigested material generally found in porcupine’s (Hystrix brachyura) gastrointestinal tract. The bezoar is traditionally used in South East Asia and Europe for the treatment of cancer, poisoning, dengue, typhoid, etc. However, limited scientific studies have been performed to verify its anticancer potential to substantiate its traditional claims in the treatment of cancers. Hence, this study was aimed at investigating the in vitro and in vivo anticancer properties of two grassy PB aqueous extract (PB-A and PB-B) using A375 cancer cell line and zebrafish model, respectively. This paper presents the first report on in vitro A375 cell viability assay, apoptosis assay, cell cycle arrest assay, migration assay, invasion assay, qPCR experimental assay and in vivo anti-angiogenesis assay using the grassy PBs. Experimental findings revealed IC50 value are 26.59 ± 1.37 μg/mL and 30.12 ± 3.25 μg/mL for PB-A and PB-B respectively. PBs showed anti-proliferative activity with no significant cytotoxic effect on normal human dermal fibroblast (NHDF). PBs were also found to induce apoptosis via intrinsic pathway and arrest cell cycle at G2/M phase. Additionally, the findings indicated its ability to debilitate migration and invasion of A375 cells. Further evaluation using embryo zebrafish model revealed LC50 = 450.0 ± 2.50 μg/mL and 58.7 ± 5.0 μg/mL for PB-A and PB-B which also exerted anti-angiogenesis effect in zebrafish. Moreover, stearic acid, ursodeoxycholic acid and pregnenolone were identified as possible metabolites that might contribute to the anticancer effect of the both PBs. Overall, this study demonstrated that PB-A and PB-B possess potential in vitro and in vivo anticancer effects which are elicited through selective cytotoxic effect, induction of apoptosis, inhibition of migration and invasion and anti-angiogenesis. This study provides scientific evidence that the porcupine bezoar do possess anti-cancer efficacy and further justifies its traditional utility. However, more experiments with higher vertebrae models are still warranted to validate its traditional claims as an anticancer agent

Chemically modified water-soluble chitosan derivatives : Modification strategies, biological activities, and applications

Chitosan, a biocompatible and nontoxic heteropolymer derived from chitin, offers various applications. However, its limited solubility above pH 6.5 hinders its broader applications. Chemical, physical, and enzymatic modifications have greatly improved chitosan properties, producing water-soluble chitosan (WSC) and derivatives. WSC and its derivatives possess unique structures, properties, and water solubility, meeting the demands of functional materials. This review highlights native chitosan characteristics, modification strategies for WSC and emphasizes its applications in food production, wastewater treatment, biomedical, and agriculture. Future perspectives for WSC and its derivatives are also discussed at the end of this paper

Determination toxic effects of Hystrix Brachyura Bezoar extracts using cancer cell lines and embryo zebrafish (Danio rerio) models and identification of active principles through GC-MS analysis

Ethnopharmacological relevance: Porcupine bezoar (PB) is used as folk medicine for various medical conditions including cancer treatment in Malaysia. However, its toxicity profile has never been thoroughly ascertained to confirm its safe nature as an efficacious traditional medicine in the treatment of cancer as well as other ailments. Aim of the study: This study was aimed to reveal three different PBs’ aqueous extracts(viz. PB-A, PB-B, PB-C) chemical constituent’s profile using GC-MS analysis, anticancer property on A375, HeLa and MCF7 cancer cells, toxicity profile on zebrafish embryo morphology, EC50, LC50 and teratogenicity index. Materials and methods: PBs’ extracts characterization was performed through GC-MS analysis, in vitro anticancer effect was carried out on A375, HeLa and MCF7 cancer cell lines and finally and toxicity properties on three different PBs aqueous extracts (viz. PB-A, PB-B, PB-C) were determined using zebrafish embryo model. Results: The GC-MS analysis revealed 10 similar compounds in all PBs’ extracts. Dilauryl thiodipropionate was found to be a major compound in all PBs’ extracts followed by tetradecanoic acid. An in vitro anticancer study revealed PB extracts exerted median inhibition concentration (IC50) <50 μg/mL, on cancer cells viz. A375, HeLa and MCF7 with no significant toxicity on normal cells viz. NHDF cells. In vivo toxicity of PBs extracts found affecting tail detachment, hatching, craniofacial, brain morphology, soft tissues, edema, spinal, somites, notochord and cardiovascular system (brachycardia, disruption of blood circulation) deformities. The LC50 and EC50 demonstrated PB extracts effect as dose and time dependent with median concentration <150.0 μg/mL. Additionally, teratogenicity index (TI) viz. >1.0 revealed teratogenic property for PB extracts. Conclusions: The findings revealed that all three PBs aqueous extracts possessed anticancer activity and exhibited significant toxicological effects on zebrafish embryos with high teratogenicity index. Hence, its use as an anticancer agent requires further investigation and medical attentions to determine its safe dose

Apoptosis inducer from Streblus asper extracts for cancer chemoprevention

One of the approaches to control cancer is prevention through consumption of fruits and vegetables which are associated with a reduced risk of cancer. The present study was undertaken to examine the chemopreventive effects of Streblus asper root extracts on osteosarcoma (HOS) and tongue carcinoma (SCC-15) cells’ growth, cell cycle modulation, apoptosis induction, and associated molecular alterations in vitro . S. asper root extract treatment on HOS and SCC-15 cells resulted in a signi fi cant decreased in cell growth with IC 50 value of 0.3 and 1%, respectively which was associated with the cell cycle phase arrest and the induction of apoptosis. Cell cycle analysis showed G2/M phase arrest in HOS and G0/G1 phase arrest in SCC-15 cells following treatment with S. asper root extracts for 72 h. This S. asper -mediated cell cycle arrest in HOS cells was accompanied with a decrease in protein levels of phosphorylated ERK ½. Induction of apoptosis was characterized by the appearance of cells with sub-G1 DNA content and the cleavage and activation of caspase 3, caspase 9 and Bcl-2 proteins. Treatment with S. asper root extract also resulted in alterations of cell morphology including cell shrinkage, vacoularization, and membrane blebbing. These fi ndings show that S. asper modulates caspase dependent pathways for inhibition of cell growth and proliferation. The extract also did not demonstrate a mutagenic effect under the condition of the test with S. typhimurium and is not considered a mutagen. The results support the use of S. asper root extract in view of the therapeutic potential and help to elucidate the reasons underlying its potentiality as chemopreventive agents

Antioxidant Activity, Total Phenolic and Flavonoid Content and LC&ndash;MS Profiling of Leaves Extracts of Alstonia angustiloba

Plants have a wide range of active compounds crucial in treating various diseases. Most people consume plants and herbals as an alternative medicine to improve their health and abilities. A. angustiloba extract showed antinematodal activity against Bursaphelenchus xylophilus, antitrypanosomal action against Trypanosoma brucei and anti-plasmodial activity against the chloroquine-resistant Plasmodium falciparum K1 strain. Moreover, it has demonstrated growth inhibitory properties towards several human cancer cell lines, such as MDA-MB-231, SKOV-3, HeLa, KB cells and A431. DPPH and ABTS assays were carried out to determine the antioxidant activity of the aqueous and 60% methanolic extract of A. angustiloba leaves. Moreover, total phenolic and flavonoid contents were quantified. The presence of potential active compounds was then screened using liquid chromatography coupled with a Q-TOF mass spectrometer (LC&ndash;MS) equipped with a dual electrospray ionisation (ESI) source. The EC50 values measured by DPPH for the 60% methanolic and aqueous extracts of A. angustiloba leaves were 80.38 and 94.11 &micro;g/mL, respectively, and for the ABTS assays were 85.80 and 115.43 &micro;g/mL, respectively. The 60% methanolic extract exhibited the highest value of total phenolic and total flavonoid (382.53 &plusmn; 15.00 mg GAE/g and 23.45 &plusmn; 1.04 mg QE/g), while the aqueous extract had the least value (301.17 &plusmn; 3.49 mg GAE/g and 9.73 &plusmn; 1.76 mg QE/g). The LC&ndash;MS analysis revealed the presence of 103 and 140 compounds in the aqueous and 60% methanolic extract, respectively. It consists of phenolic acids, flavonoids, alkaloids, amino acids, glycosides, alkaloids, etc. It can be concluded that the therapeutic action of this plant is derived from the presence of various active compounds; however, further research is necessary to determine its efficacy in treating diseases

Antioxidant Activity, Total Phenolic and Flavonoid Content and LC–MS Profiling of Leaves Extracts of <i>Alstonia angustiloba</i>

Plants have a wide range of active compounds crucial in treating various diseases. Most people consume plants and herbals as an alternative medicine to improve their health and abilities. A. angustiloba extract showed antinematodal activity against Bursaphelenchus xylophilus, antitrypanosomal action against Trypanosoma brucei and anti-plasmodial activity against the chloroquine-resistant Plasmodium falciparum K1 strain. Moreover, it has demonstrated growth inhibitory properties towards several human cancer cell lines, such as MDA-MB-231, SKOV-3, HeLa, KB cells and A431. DPPH and ABTS assays were carried out to determine the antioxidant activity of the aqueous and 60% methanolic extract of A. angustiloba leaves. Moreover, total phenolic and flavonoid contents were quantified. The presence of potential active compounds was then screened using liquid chromatography coupled with a Q-TOF mass spectrometer (LC–MS) equipped with a dual electrospray ionisation (ESI) source. The EC50 values measured by DPPH for the 60% methanolic and aqueous extracts of A. angustiloba leaves were 80.38 and 94.11 µg/mL, respectively, and for the ABTS assays were 85.80 and 115.43 µg/mL, respectively. The 60% methanolic extract exhibited the highest value of total phenolic and total flavonoid (382.53 ± 15.00 mg GAE/g and 23.45 ± 1.04 mg QE/g), while the aqueous extract had the least value (301.17 ± 3.49 mg GAE/g and 9.73 ± 1.76 mg QE/g). The LC–MS analysis revealed the presence of 103 and 140 compounds in the aqueous and 60% methanolic extract, respectively. It consists of phenolic acids, flavonoids, alkaloids, amino acids, glycosides, alkaloids, etc. It can be concluded that the therapeutic action of this plant is derived from the presence of various active compounds; however, further research is necessary to determine its efficacy in treating diseases

Novel Drug and Gene Delivery System and Imaging Agent Based on Marine Diatom Biosilica Nanoparticles

Mesoporous silica nanoparticles (MSNs) have great potential for applications as a drug delivery system (DDS) due to their unique properties such as large pore size, high surface area, biocompatibility, biodegradability, and stable aqueous dispersion. The MSN-mediated DDS can carry chemotherapeutic agents, optical sensors, photothermal agents, short interfering RNA (siRNA), and gene therapeutic agents. The MSN-assisted imaging techniques are applicable in cancer diagnosis. However, their synthesis via a chemical route requires toxic chemicals and is challenging, time-consuming, and energy-intensive, making the process expensive and non-viable. Fortunately, nature has provided a viable alternative material in the form of biosilica from marine resources. In this review, the applications of biosilica nanoparticles synthesized from marine diatoms in the field of drug delivery, biosensing, imaging agents, and regenerative medicine, are highlighted. Insights into the use of biosilica in the field of DDSs are elaborated, with a focus on different strategies to improve the physico-chemical properties with regards to drug loading and release efficiency, targeted delivery, and site-specific binding capacity by surface functionalization. The limitations, as well as the future scope to develop them as potential drug delivery vehicles and imaging agents, in the overall therapeutic management, are discussed

Bacteriostatic Activity of LLDPE Nanocomposite Embedded with Sol–Gel Synthesized TiO2/ZnO Coupled Oxides at Various Ratios

Metal oxide-polymer nanocomposite has been proven to have selective bactericidal effects against the main and common pathogens (Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli)) that can cause harmful infectious diseases. As such, this study looked into the prospect of using TiO2/ZnO with linear low-density polyethylene (LLDPE) to inactivate S. aureus and E. coli. The physical, structural, chemical, mechanical, and antibacterial properties of the nanocomposite were investigated in detail in this paper. The production of reactive species, such as hydroxyl radicals (&bull;OH), holes (h+), superoxide anion radicals (O2&bull;&macr;), and zinc ion (Zn2+), released from the nanocomposite were quantified to elucidate the underlying antibacterial mechanisms. LLDPE/25T75Z with TiO2/ZnO (1:3) nanocomposite displayed the best performance that inactivated S. aureus and E. coli by 95% and 100%, respectively. The dominant reactive active species and the zinc ion release toward the superior antibacterial effect of nanocomposite are discussed. This work does not only offer depiction of the effective element required for antimicrobial biomedical appliances, but also the essential structural characteristics to enhance water uptake to expedite photocatalytic activity of LLDPE/metal oxide nanocomposite for long term application