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Screening for the in vitro anti-tumor-promoting activities of edible plants from Malaysia

Murakami A, Ali AM, Mat-Salleh K, Koshimizu K, Ohigashi H

Biosci Biotechnol Biochem, 2000 Jan;64(1):9-16.
PMID: 10705442

A total of 114 methanol extracts from 42 plant families of edible Malaysian plants were screened for their inhibitory activities toward tumor promoter 12-O-hexadecanoylphorbol-13-acetate (HPA)-induced Epstein-Barr virus (EBV) activation in Raji cells. By testing at a concentration of 200 micrograms/ml, 74% of the 114 extracts inhibited EBV activation by 30% or more. This rate is comparable to those observed in the previous tests on edible Thai (60%) and Indonesian (71%) plants, and, importantly, much higher than that (26%) observed for Japanese edible plants. Approximately half of the Malaysian plants did not taxonomically overlap those from the other three countries, suggesting that Malaysian plants, as well as Thai and Indonesian plants, are an exclusive source of effective chemopreventive agents. Further dilution experiments indicated an extract from the leaves of Piper betle L. (Piperaceae) to be one of the most promising species. The high potential of edible Southeast Asian plants for cancer chemoprevention is collectively discussed.

Matched MeSH terms: Cell Transformation, Neoplastic/drug effects
Isolation of a quinone-rich fraction from Ardisia crispa roots and its attenuating effects on murine skin tumorigenesis

Yeong LT, Hamid RA, Yazan LS, Khaza'ai H

Asian Pac J Cancer Prev, 2013;14(4):2301-5.
PMID: 23725131

Ardisia crispa (Family: Myrsinaceae) is an evergreen, fruiting shrub that has been traditionally used as folklore medicine. Despite a scarcity of research publications, we have succeeded in showing suppressive effects on murine skin papillomagenesis. In extension, the present research was aimed at determining the effect of a quinone-rich fraction (QRF) isolated from the same root hexane extract on both initiation and promotion stages of carcinogenesis, at the selected dose of 30 mg/kg. Mice (groups I-IV) were initiated with a single dose of 7,12-dimethylbenz(α)anthracene (DMBA, 100 μg/100 μl) followed by repeated promotion of croton oil (1%) twice weekly for 20 weeks. In addition, group I (anti-initiation) received QRF 7 days before and after DMBA; group II (anti-promotion) received QRF 30 minutes before each croton oil application; group III (anti-initiation/ promotion) was treated with QRF as a combination of group I and II. A further two groups served as vehicle control (group V) and treated control (group VI). As carcinogen control, group IV showed the highest tumor volume (8.79±5.44) and tumor burden (3.60±1.17). Comparatively, group III revealed only 20% of tumor incidence, tumor burden (3.00±1.00) and tumor volume (2.40±1.12), which were significantly different from group IV. Group II also showed significant reduction of tumor volume (3.11), tumor burden (3.00) and tumor incidence (11.11%), along with prominent increase of latency period of tumor formation (week 12). Group I, nonetheless, demonstrated marked increment of tumor incidence by 40% with prompted latency period of tumor formation (week 7). No tumor formation was observed in groups V and VI. This study provided clear evidence of inhibitory effects of QRF during promotion period which was in agreement with our previous findings. The mechanism(s) underlying such effects have yet to be elucidated.

Matched MeSH terms: Cell Transformation, Neoplastic/drug effects*
Chemopreventive potential of Annona muricata L leaves on chemically-induced skin papillomagenesis in mice

Hamizah S, Roslida AH, Fezah O, Tan KL, Tor YS, Tan CI

Asian Pac J Cancer Prev, 2012;13(6):2533-9.
PMID: 22938417

Annona muricata L (Annonaceae), commonly known as soursop has a long, rich history in herbal medicine with a lengthy recorded indigenous use. It had also been found to be a promising new anti-tumor agent in numerous in vitro studies. The present investigation concerns chemopreventive effects in a two-stage model of skin papillomagenesis. Chemopreventive effects of an ethanolic extract of A. muricata leaves (AMLE) was evaluated in 6-7 week old ICR mice given a single topical application of 7,12-dimethylbenza(α)anthracene (DMBA 100 μg/100 μl acetone) and promotion by repeated application of croton oil (1% in acetone/ twice a week) for 10 weeks. Morphological tumor incidence, burden and volume were measured, with histological evaluation of skin tissue. Topical application of AMLE at 30, 100 and 300 mg/kg significantly reduced DMBA/croton oil induced mice skin papillomagenesis in (i) peri-initiation protocol (AMLE from 7 days prior to 7 days after DMBA), (ii) promotion protocol (AMLE 30 minutes after croton oil), or (iii) both peri-initiation and promotion protocol (AMLE 7 days prior to 7 day after DMBA and AMLE 30 minutes after croton oil throughout the experimental period), in a dose dependent manner (p<0.05) as compared to carcinogen-treated control. Furthermore, the average latent period was significantly increased in the AMLE-treated group. Interestingly, At 100 and 300 mg/ kg, AMLE completely inhibited the tumor development in all stages. Histopathological study revealed that tumor growth from the AMLE-treated groups showed only slight hyperplasia and absence of keratin pearls and rete ridges. The results, thus suggest that the A.muricata leaves extract was able to suppress tumor initiation as well as tumor promotion even at lower dosage.

Matched MeSH terms: Cell Transformation, Neoplastic/drug effects
Fulltext Vanillin differentially affects azoxymethane-injected rat colon carcinogenesis and gene expression

Ho KL, Chong PP, Yazan LS, Ismail M

J Med Food, 2012 Dec;15(12):1096-102.
PMID: 23216109 DOI: 10.1089/jmf.2012.2245

Vanillin is the substance responsible for the flavor and smell of vanilla, a widely used flavoring agent. Previous studies reported that vanillin is a good antimutagen and anticarcinogen. However, there are also some contradicting findings showing that vanillin was a comutagen and cocarcinogen. This study investigated whether vanillin is an anticarcinogen or a cocarcinogen in rats induced with azoxymethane (AOM). Rats induced with AOM will develop aberrant crypt foci (ACF). AOM-challenged rats were treated with vanillin orally and intraperitoneally at low and high concentrations and ACF density, multiplicity, and distribution were observed. The gene expression of 14 colorectal cancer-related genes was also studied. Results showed that vanillin consumed orally had no effect on ACF. However, high concentrations (300 mg/kg body weight) of vanillin administered through intraperitoneal injection could increase ACF density and ACF multiplicity. ACF were mainly found in the distal colon rather than in the mid-section and proximal colon. The expression of colorectal cancer biomarkers, protooncogenes, recombinational repair, mismatch repair, and cell cycle arrest, and tumor suppressor gene expression were also affected by vanillin. Vanillin was not cocarcinogenic when consumed orally. However, it was cocarcinogenic when being administered intraperitoneally at high concentration. Hence, the use of vanillin in food should be safe but might have cocarcinogenic potential when it is used in high concentration for therapeutic purposes.

Matched MeSH terms: Cell Transformation, Neoplastic/drug effects
Inhibitory effect of phenethyl isothiocyanate against benzo[a] pyrene-induced rise in CYP1A1 mRNA and apoprotein levels as its chemopreventive properties

Abdull Razis AF, Konsue N, Ioannides C

Asian Pac J Cancer Prev, 2015;16(7):2679-83.
PMID: 25854346

BACKGROUND: Phenethyl isothiocyanate (PEITC), the most comprehensively studied aromatic isothiocyanate, has been shown to act as an anti-cancer agent mainly through modulation of biotransformation enzymes responsible for metabolizing carcinogens in the human body. Humans are often exposed to carcinogenic factors, some of which through the diet, such as polycyclic aromatic hydrocarbon benzo[a]pyrene via the consumption of over-cooked meats. Inhibition of the enzymes responsible for the bioactivation of this carcinogen, for example CYP1A1, the major enzyme required for polycyclic aromatic hydrocarbons (PAHs) bioactivation, is recognized as a chemoprevention strategy.
OBJECTIVE: To evaluate the inhibitory effects of PEITC against benzo[a]pyrene-induced rise in rat liver CYP1A1 mRNA and apoprotein levels.
MATERIALS AND METHODS: Precision cut rat liver slices were treated with benzo[a]pyrene at 1 and 5 μM in the presence of PEITC (1-25 μM) for 24 hours, followed by determination of CYP1A1 mRNA and apoprotein levels using quantitative polymerase chain reaction and immunoblotting.
RESULTS: Findings revealed that PEITC inhibited benzo[a]pyrene-induced rise in rat liver CYP1A1 mRNA in a dose-dependent manner as well as the apoprotein levels of CYP1A.
CONCLUSIONS: It was demonstrated that PEITC can directly inhibit the bioactivation of benzo[a]pyrene, indicating chemopreventive potential.

Matched MeSH terms: Cell Transformation, Neoplastic/drug effects*
Long-term administration of tocotrienols and tumor-marker enzyme activities during hepatocarcinogenesis in rats

Rahmat A, Ngah WZ, Shamaan NA, Gapor A, Abdul Kadir K

Nutrition, 1993 May-Jun;9(3):229-32.
PMID: 8102564

The effects of long-term administration of tocotrienol on hepatocarcinogenesis in rats induced by diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) were investigated by determining the activities of gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), glutathione S-transferases (GSTs), and glutathione (GSH) levels in blood and liver. Twenty-eight male 7- to 8-wk-old Rattus norwegicus rats, weighing 120-160 g, were used in this study. The rats were divided into four treatment groups: a control group on a basal diet, a group fed a basal diet supplemented with tocotrienol (30 mg/kg food), a group treated with DEN/AAF, and a group treated with DEN/AAF and fed a diet supplemented with tocotrienol (30 mg/kg food). Blood was collected monthly, and GGT, ALP, and GSH levels were determined. The rats were killed after 9 mo, and the livers were examined morphologically. Grayish white nodules (2/liver) were found in all the DEN/AAF-treated rats (n = 10), but only one of the rats treated with DEN/AAF and supplemented with tocotrienol (n = 6) had liver nodules. A significant increase in the level of blood and liver GSH, ALP, and GGT activities was observed in the DEN/AAF-treated rats. Liver GSTs were similarly increased with DEN/AAF treatment. Tocotrienol supplementation attenuated the impact of the carcinogens in the rats.

Matched MeSH terms: Cell Transformation, Neoplastic/drug effects*
Fulltext Low dose triterpene-quinone fraction from Ardisia crispa root precludes chemical-induced mouse skin tumor promotion

Yeong LT, Abdul Hamid R, Saiful Yazan L, Khaza'ai H, Mohtarrudin N

BMC Complement Altern Med, 2015;15(1):431.
PMID: 26638207 DOI: 10.1186/s12906-015-0954-3

Drastic increment of skin cancer incidence has driven natural product-based chemoprevention as a promising approach in anticancer drug development. Apart from its traditional usages against various ailments, Ardisia crispa (Family: Myrsinaceae) specifically its triterpene-quinone fraction (TQF) which was isolated from the root hexane extract (ACRH) was recently reported to exert antitumor promoting activity in vitro. This study aimed at determining chemopreventive effect of TQF against chemically-induced mouse skin tumorigenesis as well as elucidating its possible pathway(s).

Matched MeSH terms: Cell Transformation, Neoplastic/drug effects
The impact of capsaicin intake on risk of developing gastric cancers: a meta-analysis

Pabalan N, Jarjanazi H, Ozcelik H

J Gastrointest Cancer, 2014 Sep;45(3):334-41.
PMID: 24756832 DOI: 10.1007/s12029-014-9610-2

BACKGROUND: Reported associations of capsaicin with gastric cancer development have been conflicting. Here, we examine 10 published articles that explore these associations using 2,452 cases and 3,996 controls.
METHODS: We used multiple search strategies in MEDLINE through PubMed to seek for suitable articles that had case-control design with gastric cancer as outcome.
RESULTS: The outcomes of our study shows protection (odds ratio [OR] 0.55, P = 0.003) and susceptibility (OR 1.94, P = 0.0004), both significant with low and medium-high intake of capsaicin, respectively, although under relatively heterogeneous conditions (P(heterogeneity) = <0.0001). Outlier analysis resulted in loss of overall heterogeneity (P = 0.14) without affecting the pooled ORs. Among the subgroups, low intake elicited protection in both Korean (OR 0.37) and Mexican (OR 0.63) populations while high intake rendered these subgroups susceptible (OR 2.96 and OR 1.57, respectively). These subgroup values were highly significant (P = 0.0001-0.01) obtained in heterogeneous conditions (P(heterogeneity)

Matched MeSH terms: Cell Transformation, Neoplastic/drug effects
Nuclear factor-kappa B as a promising target for selenium chemoprevention in rat hepatocarcinogenesis

Alwahaibi NY, Budin SB, Mohamed J, Alhamdani A

J Gastroenterol Hepatol, 2010 Apr;25(4):786-91.
PMID: 20492335 DOI: 10.1111/j.1440-1746.2009.06160.x

Selenium's molecular mechanism for cancer chemoprevention remains unknown. We aimed to study the gene expression of nuclear factor-kappaB (NF-kappaB), tumor growth factor-alpha (TGF-alpha) and cyclin D1 and the effects of sodium selenite using preventive and therapeutic approaches in chemically-induced hepatocarcinogenesis in rats.

Matched MeSH terms: Cell Transformation, Neoplastic/drug effects*
Fulltext Anti-tumor effect of Ardisia crispa hexane fraction on 7, 12-dimethylbenz[α]anthracene-induced mouse skin papillomagenesis

Sulaiman H, Hamid RA, Ting YL, Othman F

J Cancer Res Ther, 2012 Jul-Sep;8(3):404-10.
PMID: 23174723 DOI: 10.4103/0973-1482.103521

CONTEXT: Ardisia crispa Thunb. A. DC (Myrsinaceae) or locally known as hen's eyes has been used in local folk medicine as a remedy in various illnesses. Previously, it has been reported to inhibit various inflammatory diseases. However, research done on this plant is still limited.
AIMS: In the present study, the hexane fraction of the A. crispa root (ACRH) was evaluated on the peri-initiation and promotion phases of skin carcinogenesis.
MATERIALS AND METHODS: This two-stage skin carcinogenesis was induced by a single topical application of 7,12-dimethylbenz(α)anthracene (DMBA) and promoted by repeated treatment with croton oil for 10 weeks in Imprinting Control Region (ICR) mice. Morphological observation would be conducted to measure tumor incidence, tumor burden, and tumor volume. Histological evaluation on the skin tissue would also be done.
RESULTS: The carcinogen control group exhibited 66.67% of tumor incidence. Although, in the ACRH-treated groups, at 30 mg/kg, the mice showed only 10% of tumor incidence with a significant reduction (P < 0.05) in the values of tumor burden and tumor volume of 2.00 and 0.52 mm(3), respectively. Furthermore, the result was significantly lower than that of the carcinogen and curcumin control. At 100 mg/kg, ACRH showed a comparable result to carcinogen control. On the contrary, at 300 mg/kg, ACRH exhibited 100% tumor incidence and showed a significant elevated (P < 0.05) value of tumor burden (3.80) and tumor volume (14.67 ± 2.48 mm(3)).
CONCLUSIONS: The present study thus demonstrates that the anti-tumor effect of the chemopreventive potential of ACRH is at a lower dosage (30 mg/kg bwt) in both the initiating and promotion period, yet it exhibits a promoting effect at a higher dosage (300 mg/kg bwt).

Matched MeSH terms: Cell Transformation, Neoplastic/drug effects
Effect of cacao liquor extract on tumor marker enzymes during chemical hepatocarcinogenesis in rats

Amin I, Koh BK, Asmah R

J Med Food, 2004;7(1):7-12.
PMID: 15117546

This study investigated the effect of cacao liquor extract (CLE) on tumor marker enzymes--alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), glutathione-S-transferase (GST), and glutathione reductase (GR) activities--in plasma and/or liver of hepatocarcinogenic rats, which were induced with diethylnitrosamine and 2-acetylaminofluorene. Twenty-nine male Sprague-Dawley rats (weighing 150-330 g) were divided into four groups (n = 6-8): normal control group (N), normal group + CLE (NE), cancer group (C), and cancer group + CLE (CE). Analysis of variance showed significant differences (P

Matched MeSH terms: Cell Transformation, Neoplastic/drug effects
Fulltext Chemopreventive Activity of Ferulago angulate against Breast Tumor in Rats and the Apoptotic Effect of Polycerasoidin in MCF7 Cells: A Bioassay-Guided Approach

Karimian H, Fadaeinasab M, Zorofchian Moghadamtousi S, Hajrezaei M, Razavi M, Safi SZ, et al.

PLoS One, 2015;10(5):e0127434.
PMID: 25996383 DOI: 10.1371/journal.pone.0127434

Ferulago angulata leaf hexane extract (FALHE) was found to be a potent inducer of MCF7 cell apoptosis. The aims of the present study were to investigate the in vivo chemopreventive effect of FALHE in rats, to identify the contributing anticancer compound in FALHE and to determine its potential mechanism of action against MCF7 cells. Thirty rats harboring LA7-induced breast tumors were divided into five groups: tumor control, low-dose FALHE, high-dose FALHE, treatment control (tamoxifen) and normal control. Breast tissues were then subjected to histopathological and immunohistochemical analyses. A bioassay-guided investigation on FALHE was performed to identify the cytotoxic compound and its mechanism of action through flow cytometry, real-time qPCR and western blotting analyses. An in vivo study showed that FALHE suppressed the expression of the tumor markers PCNA and Ki67. The tumor size was reduced from 2031 ± 281 mm3 to 432 ± 201 mm3 after FALHE treatment. FALHE administration induced apoptosis in breast tumor cells, and this was confirmed by high expression levels of Bax, p53 and caspase 3. Cell cycle arrest was suggested by the expression of p21 and p27. The in vitro experimental results resulted in the isolation of polycerasoidin as a bioactive ingredient of FALHE with an IC50 value of 3.16 ± 0.31 μg/ml against MCF7 cells. Polycerasoidin induced mitochondrial-dependent apoptosis in breast cancer cells via caspase activation and changes in the mRNA and protein expression of Bax and Bcl-2. In addition, flow cytometric analysis demonstrated that the treated MCF7 cells were arrested at the G1 phase, and this was associated with the up-regulation of p21 and p27 at both the mRNA and protein levels. The results of the present study reinforce further investigations scrutinizing the promising potential of the F. angulata chemical constituents as breast cancer chemopreventive agents.

Matched MeSH terms: Cell Transformation, Neoplastic/drug effects

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