Anti-Oxidative Effect of Myrtenal in Prevention and Treatment of Colon Cancer Induced by 1, 2-Dimethyl Hydrazine (DMH) in Experimental Animals.

Colon cancer is considered as the precarious forms of cancer in many developed countries, with few to no symptoms; the tumor is often diagnosed in the later stages of cancer. Monoterpenes are a major part of plant essential oils found largely in fruits, vegetables and herbs. The cellular and molecular activities show therapeutic progression that may reduce the risk of developing cancer by modulating the factors responsible for colon carcinogenesis. Colon cancer was induced with DMH with a dose of (20 mg/Kg/body weight) for 15 weeks by subcutaneous injection once in a week. Myrtenal treatment was started with (230 mg/Kg/body weight) by intragastric administration, one week prior to DMH induction and continued till the experimental period of 30 weeks. The Invivo results exhibit the elevated antioxidant and lipid peroxidation levels in DMH treated animals. The Histopathological analysis of colon tissues well supported the biochemical alterations and inevitably proves the protective role of Myrtenal. Treatment with myrtenal to cancer bearing animals resulted in a remarkable increase in the inherent antioxidants and excellent modulation in the morphological and physiological nature of the colon tissue. It is thus concluded that myrtenal exhibits excellent free radical scavenging activity and anticancer activity through the suppression of colon carcinoma in Wistar albino rats.

D-pinitol mitigates tumor growth by modulating interleukins and hormones and induces apoptosis in rat breast carcinogenesis through inhibition of NF-κB.

Breast cancer is the most prevalent malignant neoplasm in the world, and chemoprevention through dietary intervention strategy is an emerging option to reduce the incidence. D-pinitol (DP), a major component of soya bean, possesses attractive biological actions. We have investigated whether D-pinitol have an effect on tumor growth in vivo against 7,12-dimethylbenz(a)anthracene (DMBA)-initiated rat mammary carcinogenesis and investigated its mechanism of action. Tumors were induced in Sprague-Dawley (SD) rats by a gastric dose of 20 mg/kg DMBA, and after 13 weeks of induction period, the rats were orally administered with D-pinitol for 45 days. At the end of the assay, animals in carcinogen control group prompted a tumor incidence of 100 % and developed a tumor volume of 8.35 ± 0.56, which was significantly reduced to 5.74 ± 0.32 for the animals treated with D-pinitol. The D-pinitol treatment not only decreased the tumor volume but also further examination revealed that tumors from animals that received D-pinitol reduced nuclear factor kappa B (NF-κB) activation which in turn results in modulation of its downstreaming p53 and proteins of caspase-3 family. Bcl-2 expression and caspase-3 activation were also decreased after D-pinitol supplementation leading to induction of apoptosis and finally cell death. Furthermore, the status of the inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-2, IL-6, and tumor markers, lipid profile, and hormones was also significantly declined up on D-pinitol administration. Thus, it reveals the collective involvement of the above-mentioned parameters along with NF-κB signaling through which D-pinitol induces apoptosis and subsequently suppresses breast cancer during DMBA-induced rat breast carcinogenesis.

D-Pinitol Protects Against Carbon Tetrachloride-Induced Hepatotoxicity in Rats.

The aim of the study was to evaluate the protective activity of D-Pinitol against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. The animals were divided into six groups, with each group consisting of six animals. Group I animals served as normal controls and received olive oil vehicle (1.0 ml/kg body weight intraperitoneally). Group II rats served as CCl4 controls, which received 30% CCl4 suspended in olive oil (3.0 ml/kg body weight intraperitoneally) twice a week for 4 weeks. Group III rats were treated with 30% CCl4 suspended in olive oil (3.0 ml/kg body weight intraperitoneally) twice a week for 4 weeks, followed by D-Pinitol (100 mg/kg body weight) given for 28 days intragastrically. Group IV rats received D-Pinitol alone at a concentration of 100 mg/kg body weight for 28 days intragastrically. At the end of the experimental period, serum marker enzymes and lipid peroxidation (LPO) levels were significantly increased in group II animals. On the other hand, D-Pinitol treatment significantly decreased marker enzymes and LPO levels and increased the antioxidant level. CYP expression was also investigated. Therefore, the present study revealed that D-Pinitol acts as a protective agent by decreasing metabolic activation of xenobiotics through its antioxidant nature.

D-pinitol promotes apoptosis in MCF-7 cells via induction of p53 and Bax and inhibition of Bcl-2 and NF-κB.

Development of drugs from natural products has been undergoing a gradual evoluation. Many plant derived compounds have excellent therapeutic potential against various human ailments. They are important sources especially for anticancer agents. A number of promising new agents are in clinical development based on their selective molecular targets in the field of oncology. D-pinitol is a naturally occurring compound derived from soy which has significant pharmacological activitites. Therefore we selected D-pinitol in order to evaluate apoptotic potential in the MCF-7 cell line. Human breast cancer cells were treated with different concentrations of D-pinitol and cytotoxicity was measured by MTT and LDH assays. The mechanism of apoptosis was studied with reference to expression of p53, Bcl-2, Bax and NF-kB proteins. The results revealed that D-pinitol significantly inhibited the proliferation of MCF-7 cells in a concentration-dependent manner, while upregulating the expression of p53, Bax and down regulating Bcl-2 and NF-kB. Thus the results obtained in this study clearly vindicated that D-pinitol induces apotosis in MCF-7 cells through regulation of proteins of pro- and anti-apoptotic cascades.

Cancer preventive efficacy of marine carotenoid fucoxanthin: cell cycle arrest and apoptosis.

Epidemiological investigations have shown that overcoming the risk of cancer is related to the consumption of green vegetables and fruits. Many compounds from different origins, such as terrestrial plants and marine and microbial sources, have been reported to have therapeutic effects of which marine sources are the most important because the diversity of marine life is more varied than other sources. Fucoxanthin is one important compound with a marine origin and belongs to the group of carotenoids; it can be found in marine brown seaweeds, macroalgae, and diatoms, all of which have remarkable biological properties. Numerous studies have shown that fucoxanthin has considerable medicinal potential and promising applications in human health. In this review, we summarize the anticancer effects of fucoxanthin through several different mechanisms including anti-proliferation, induction of apoptosis, cell cycle arrest and anti-angiogenesis, and its possible role in the treatment of cancer.

Diosgenin, a steroidal saponin, exhibits anticancer activity by attenuating lipid peroxidation via enhancing antioxidant defense system during NMU-induced breast carcinoma.

Diosgenin, a natural steroidal saponin, has been reported to be found predominantly in fenugreek and has diverse biological properties. N-Methyl-N-nitrosourea (NMU) is a mammary gland-specific carcinogen that closely mimics human breast cancer in many aspects. The aim of this study was to investigate the anticarcinogenic property of diosgenin with reference to lipid peroxidation, status of antioxidants, and activities of marker enzymes against NMU-induced experimental mammary carcinogenesis. Breast cancer was induced in female Sprague Dawley rats by an intraperitoneal administration of a single dose of NMU (a concentration of 50 mg/kg body weight) diluted in 0.9% saline, and the rats were treated with oral diosgenin, 20 mg/kg body weight, for 45 days. The results were interesting, and the diosgenin treatment remarkably downregulated the peroxidation reaction and marker enzymes and extraordinarily enhanced the indigenous antioxidant defense system. The factor for this remarkable restoration might be due to the effect of the intervention strategy on the downregulation of the peroxidation reaction through the strong antioxidant nature, which ultimately reflected in the downregulation of marker enzyme activities. The histopathological study of breast and liver tissues inevitably confirms the biochemical changes. Thus, it can be concluded that diosgenin exhibits anticarcinogenic activity via reducing peroxidation reaction and marker enzymes through enhancing the intrinsic antioxidant defense system.

D-Pinitol attenuates 7, 12 dimethylbenz [a] anthracene induced hazards through modulating protein bound carbohydrates, adenosine triphosphatases and lysosomal enzymes during experimental mammary carcinogenesis.

We have reported here that the ameliorative potentials of D-Pinitol during 7, 12-Dimethylbenz [a] anthracene induced experimental breast carcinogenesis. DMBA is a potent organ specific carcinogen which is widely employed to induce mammary carcinoma in rats. D-Pinitol a natural inositol has been reported to found in soybean with many biological functions. The female sprague dawley rats were subjected to carcinogen 7, 12-DMBA and the ameliorative potentials of dietary compound D-Pinitol was investigated with reference to cell surface glycoproteins, lysosomal enzymes and adenosine triphosphatases. Interestingly, administration of D-Pinitol was found to be significantly down regulated the breast tissue glycoproteins and lysosomal enzymes and in contrast the levels of adenosine triphosphatases were remarkably up regulated. Further, the biochemical changes were well reflected and evidenced in the histology of breast and liver tissues. Thus, it can be concluded from the present study that D-Pinitol efficiently attenuates the hazardous consequences of the environmental carcinogen 7,12-DMBA through modulating cell surface glycoproteins, membrane protective role both in lysosomal and ATPase compartment via its antioxidant nature which ultimately results in the findings of future innovative remedies for genotoxin mediated hazards.

Myrtenal, a natural monoterpene, down-regulates TNF-α expression and suppresses carcinogen-induced hepatocellular carcinoma in rats.

Hepatocellular carcinoma is one of the most common cancers and lethal diseases in the world. Recently, many researchers focused to identify novel chemotherapeutic agents from natural sources against hepatocarcinogenesis. The diverse therapeutic potential of essential oils has drawn the attention of researchers to test them for anticancer activity, taking advantage of the fact that their mechanism of action is dissimilar to that of chemotherapeutic agents. Earlier reports indicated that essential oil components, especially monoterpenes, have multiple pharmacological effects which could account for the terpene-tumor suppressive activity. In the present study, it is shown that myrtenal, a natural monoterpene, which acts as an antineoplastic agent against diethylnitrosamine induced phenobarbital promoted experimental hepatocellular carcinoma. The results revealed an elevated level of microsomal lipid peroxidation in the liver, which was found to be significantly reduced by myrtenal treatment. On the contrary, the Phase I hepatic drug metabolizing enzymes' (cytochrome P(450), cytochrome b(5), NADPH-cytochrome c reductase, NADH-cytochrome b(5) reductase) levels were decreased and the Phase II enzymes (glutathione-S-transferase, uridine 5'-diphospho-glucuronyl transferase) were increased in carcinogen-administered animals, which were reverted to near normalcy upon myrtenal administration. Our findings also showed that myrtenal restrains the liver cancer by preventing the DEN-PB induced up-regulation of TNF-α protein expression by immunoblot. Furthermore, transmission electron microscopic examination also indicated that myrtenal prevents the carcinogen-induced changes in the architecture of liver tissue and cell structure. Thus, this study shows that myrtenal has the ability to suppress the hepatocellular carcinoma in rats.

Myrtenal attenuates diethylnitrosamine-induced hepatocellular carcinoma in rats by stabilizing intrinsic antioxidants and modulating apoptotic and anti-apoptotic cascades.

BACKGROUND: Myrtenal, a natural monoterpene occurred in cumin, pepper, mint and eucalyptus. Monoterpenes are naturally occurring plant hydrocarbons composed of two isoprene units and are widely distributed in plant flora and are best known for occurrence in essential oils. Monoterpenes have been shown to have remarkable biological activities such as antioxidant, chemotherapeutic and chemopreventive effects in different models of cancer. The aim of the study was to investigate the antioxidant and anticancer activity of myrtenal against carcinogen induced hepatocellular caricinoma in rats. METHODS: The antioxidant properties of myrtenal were evaluated by using different in vitro antioxidant assays such as by determining its scavenging effect against hydroxyl (OH(•)), superoxide anion (O2(•-)), nitric oxide, 1,1-diphenyl-2-picrylhydrazyl (DPPH(•)) and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid radical cation (ABTS(•+)). In vivo antioxidant and anticancer activity of myrtenal were evaluated by determining the antioxidant enzymes, apoptotic and anti-apoptotic proteins such as Bcl-2, Bax and caspase-3 expression and histopathological analysis against the diethylnitrosamine induced hepatocellular carcinoma in wistar albino rats. RESULTS: Our results demonstrated that myrtenal exhibits strong antioxidant property in all the in vitro assays and the in vivo results revealed that the antioxidant status was significantly decreased in hepatoma bearing animals. The expression of anti-apoptotic proteins was up regulated and in contrast the apoptotic protein was down regulated in hepatoma bearing animals. Treatment with myrtenal to cancer bearing animals resulted in remarkable increase in the inherent antioxidants and excellent modulation in the proteins of apoptotic and anti-apoptotic cascade. Further, the RT-PCR analysis of protein expressions and histological analysis of liver tissues inevitably confirms the anticancer property of myrtenal. CONCLUSIONS: It is concluded that myrtenal exhibits excellent free radical scavenging activity and anticancer activity through the suppression of hepatocellular carcinoma in wistar rats. Thereby giving a positive insight to take this compound as an effective therapeutic agent against hepatoma.

Influence of hesperidin on renal cell surface glycoprotein content, nucleic acids, lysosomal enzymes and macromolecules against 7, 12-dimethylbenz [a] anthracene induced experimental breast carcinoma.

Therapeutic substances may reduce the risk of developing cancer by modulating the factors responsible for carcinogenesis. To evaluate these hypotheses, the present study was designed to investigate the modulatory effect of bioflavonoid "Hesperidin" against DMBA induced experimental breast cancer with reference to renal cell surface glycoproteins, nucleic acids, protein content, lipid profile and lysosomal enzymes. The female sprague-dawley rats were orally administered with single dose of 7, 12-DMBA to induce breast cancer and were treated with hesperidin [30 mg/kg/body weight] for a consecutive 45 days. The results revealed that there was a significant elevation in the levels of glycoproteins, nucleic acids, lysosomal enzymes and also significant alterations in macromolecules in renal tissues of cancer bearing animals. Interestingly, the altered levels of these parameters were remarkably reverted back to near normal in hesperidin treatment. The histopathological analysis of liver and kidney tissues were well supported the biochemical alterations and inevitably proves the protective role of hesperidin. It is proposed that, the effect of hesperidin during DMBA induced breast cancer could be due to the intervention strategies of hesperidin in the protein, nucleic acid biosynthesis, membrane stabilizing potentials on lysosomal compartment and inhibitory effect on cell surface glycoproteins and bio-fuel such as lipids.

Hesperidin a citrus bioflavonoid modulates hepatic biotransformation enzymes and enhances intrinsic antioxidants in experimental breast cancer rats challenged with 7, 12-dimethylbenz (a) anthracene.

DMBA is a major class of potent genotoxic chemical carcinogen present in the environment and it may increase breast cancer risk. Flavonoids have been shown to have interesting biological activities in many experimental investigations. Hesperidin is one of the citrus flavonoid shown to be active against various oxidative stress mediated diseases. The aim of the present study was to investigate the beneficial impact of a natural citrus flavonoglycoside hesperidin against 7, 12-Dimethylbenz [a] anthracene challenged experimental breast carcinogenesis with reference to drug metabolizing enzymes and intrinsic antioxidant status. The female Sprague-Dawley rats were orally administered with single dose of 7, 12-DMBA to induce breast cancer and were treated with hesperidin [30mg/kg/body weight] for a consecutive 45 days. The results revealed that there was a significant reduction in the status of antioxidants levels and also significant alterations in the drug metabolizing enzymes were found in genotoxin DMBA exposed animals. Interestingly these, altered levels were significantly revered back to near normal in hesperidin administered animals via enhancing the intrinsic antioxidant levels and induction in Phase II enzymes and modulation in Phase I enzyme levels. Thus the antigenotoxic activity of hesperidin may be due to the modulatory effect in biotransformation enzymes and excellent antioxidant potentials which paving a way to consider hesperidin against the genotoxin involved oxidative stress mediated diseases.

Chemotherapeutic Efficacy of Indigofera aspalathoides on 20-Methylcholanthrene-Induced Fibrosarcoma in Rats.

The present study was undertaken to test the chemopreventive effects of one herbal medicinal plant, Indigofera aspalathoides, on chemically induced carcinogenesis in rats. A well-known polyaromatic hydrocarbon, namely, 20-methylcholanthrene, which is a known carcinogenic substance, was used to induce fibrosarcoma in Wistar strain of male albino rats. Fibrosarcoma rats were treated with aqueous extracts of Indigofera aspalathoides. The rats were divided into four groups, each consisting of six animals. Group I served as normal control, Group II served as fibrosarcoma-induced animals, Group III were fibrosarcoma-bearing animals treated with aqueous extracts of Indigofera aspalathoides, and Group IV animals, which were normal healthy animals treated with Indigofera aspalathoides aqueous extract, served as drug control set. Group III and Group IV animals were treated with aqueous extract of Indigofera aspalathoides intraperitoneally at a dose of 250 mg/kg. b.w. for 30 days. The fibrosarcoma was proved by pathological examinations. The activity levels of nucleic acids such as total DNA and RNA and hexose, hexosamine, and sialic acid in liver and kidney of treated rats were used to monitor the chemopreventive role of the plant extract. The observed increase in the levels of DNA, RNA, hexose, hexosamine, and sialic acid in liver and kidney tissues of fibrosarcoma-bearing animals reached near normal state after the treatment with aqueous extracts of Indigofera aspalathoides, suggesting that Indigofera aspalathoides does have a chemotherapeutic role.

Antiproliferative role of Indigofera aspalathoides on 20 methylcholanthrene induced fibrosarcoma in rats.

OBJECTIVE: To find out the anticancer effect of Indigofera aspalathoides (I. aspalathoides) on 20-methylcholanthrene induced fibrosarcoma in rats. METHODS: Fibrosarcoma was induced in Wistar strain male albino rats by 20-methylcholanthrene. Intraperitoneous (i.p.) administration of 250 mg/kg body weight/day of aqueous extract of I. aspalathoides for 30 d effectively suppressed chemically induced tumors. Parameters such as body weight, liver and kidney weight, tumor weight, mean survival time, behavioral changes, blood glucose, blood glycogen and marker enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), acid phosphatase (ACP) and 5'-nucleiotidase (5'-NT) in serum, liver and kidney and lipid profiles such as total cholesterol, phospholipids, free fatty acids in liver and kidney of control and experimental animals were studied. RESULTS: Fibrosarcoma bearing animals were ferocious and anxious. The mean survival time was found to increase after the treatment. The body weights were significantly decreased (P<0.001) in group II fibrosarcoma animals which steadily increased after the treatment with I. aspalathoides. The liver and kidney weights were significantly increased whereas the tumor weights decreased as compared to the weights in untreated fibrosarcoma bearing rats. The blood glucose and the liver and kidney glycogen levels were found to decrease significantly (P<0.001) in group II animals. Elevated activities of marker enzymes were observed in serum, liver and kidney of fibrosarcoma bearing Group II animals which were normalize after I. aspalathoides treatment. In the liver and kidney of Group II animals the total cholesterol increased whereas the phospholipids and free fatty acid levels decreased (P<0.001) which were normalized after treatment. CONCLUSIONS: The treatment by I. aspalathoides on fibrosarcoma bearing rats has improved the levels of various parameters indicating its antiproliferative and anticancer activity.

Hesperidin protects renal and hepatic tissues against free radical-mediated oxidative stress during DMBA-induced experimental breast cancer.

Hesperidin has been reported to have an excellent and wide variety of biological activities. This property has brought the compound to a new stage in the treatment of various oxidative stress-mediated diseases. The present investigation was aimed to evaluate the therapeutic potential of hesperidin by assaying the activities of antioxidant enzymes, lipid peroxidation, membrane bound marker enzymes, adenosine triphosphates, and TCA cycle enzymes, especially in kidney tissues during 7,12-dimethybenz(a)anthracene-induced breast cancer. Daily oral administration of hesperidin (30 mg/kg body wt) to breast cancer-bearing rats for 45 days demonstrated a significant (P < .05) decline in renal lipid peroxidation and membrane bound marker enzymes, as well as a remarkable increase in adenosine triphosphatases, mitochondrial functional enzymes, and renal antioxidants. Furthermore, histological studies of liver and kidney provided evidence of biochemical alterations. Thus, the protective effects of hesperidin on attenuating the peroxidation reaction and membrane bound marker enzyme activities as well as upregulation of adenosine triphosphatases, TCA cycle enzymes, and antioxidants suggest promising uses of flavonoglycoside hesperidin in the future treatment of oxidative stress-mediated diseases.

Effects of Terminalia arjuna bark extract on apoptosis of human hepatoma cell line HepG2.

AIM: To investigate the effects of Terminalia arjuna (T. arjuna) extract on human hepatoma cell line (HepG2) and its possible role in induction of apoptosis. METHODS: Human hepatoma cells were treated with different concentrations of ethanolic extract of T. arjuna and its cytotoxicity effect was measured by trypan blue exclusion method and lactate dehydrogenase leakage assay. Apoptosis was analyzed by light and fluorescence microscopic methods, and DNA fragmentation. The mechanism of apoptosis was studied with expression of p53 and caspase-3 proteins. Glutathione (GSH) content was also measured in HepG2 cells after T. arjuna treatment. RESULTS: T. arjuna inhibited the proliferation of HepG2 cells in a concentration-dependent manner. Apoptotic morphology was observed in HepG2 cells treated with T. arjuna at the concentrations of 60 and 100 mg/L. DNA fragmentation, accumulation of p53 and cleavage of procaspase-3 protein were observed in HepG2 cells after the treatment with T. arjuna. The depletion of GSH was observed in HepG2 cells treated with T. arjuna. CONCLUSION: T. arjuna induced cytotoxicity in HepG2 cells in vitro. Apoptosis of HepG2 cells may be due to the DNA damage and expression of apoptotic proteins. Depletion of GSH may be involved in the induction of apoptosis of HepG2 cells.

Antioxidant activity of Terminalia arjuna bark extract on N-nitrosodiethylamine induced hepatocellular carcinoma in rats.

The present investigation was carried out to evaluate the antioxidant nature of ethanolic extract of Terminalia arjuna bark (EETA) on N-nitrosodiethylamine (DEN) induced liver cancer in male Wistar albino rats. Liver cancer was induced by single intraperitonial injection of DEN (200 mg/kg). After 2 weeks of DEN administration, Phenobarbital (PB) was given to promote the cancer for up to 14 successive weeks. EETA extract (400 mg/kg) was given post-orally for 28 days to hepatocellular carcinoma-bearing rats. After the experimental period, all the animals were sacrificed and serum, liver and kidney samples were collected for further biochemical analysis. The levels of lipid peroxides (LPO) under basal and also in the presence of inducers (H(2)O(2), ascorbate and FeSO(4)) were estimated in serum, liver and kidney of control and experimental animals. Enzymic antioxidants, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non-enzymic antioxidants like Vitamin C (Vit-C) and Vitamin E (Vit-E) levels were determined in all the groups of animals. A significant increase in LPO levels were observed while the levels of enzymic and non-enzymic antioxidants were decreased, when subjected to DEN induction. These altered enzyme levels were ameliorated significantly by administration of EETA at the concentration of 400 mg/kg in drug-treated animals. This protective effect of EETA was associated with inhibition of LPO induced by DEN and to maintain the antioxidant enzyme levels. Our results show an antioxidant activity of T. arjuna bark against DEN-induced liver cancer.