Akt/survivin pathway inhibition enhances the apoptotic cell death-induced by alpha-santalol in human prostate cancer cells.

We have shown previously that alpha-santalol, a major component of sandalwood oil inhibits growth of cultured prostate cancer cells in vitro by causing apoptosis, but the mechanism of cell death is not fully elucidated. The present study was undertaken to investigate the role of PI3K/Akt/survivin pathway in alpha-santalol-induced apoptosis employing cultured LNCaP and PC-3 human prostate cancer cells. Treatment of prostate cancer cells with alpha-santalol (20, 40 µM) resulted in the down regulation of survivin and p-AKT (s-473) expression and statistically significant reduction in total survivin levels as evidenced by survivin ELISA assay. Furthermore, inhibition of PI3K-Akt pathway by pharmacological inhibitor, LY294002 enhanced the apoptotic cell death induced by alpha-santalol as determined by cell viability, cellular morphology, active caspase-3 activity and expression of cleaved PARP, cleaved caspase-3 levels. In conclusion, the present study provides novel insight into the molecular circuitry of alpha-santalol-induced cell death and reveals that alpha-santalol targets Akt/Survivin pathway to induce cell death and that the cell death is increased in the presence of a known inhibitor of the pathway.

Medicinal properties of alpha-santalol, a naturally occurring constituent of sandalwood oil: review.

Alpha-santalol is a naturally occurring sesquiterpene that is derived from sandalwood oil. Its wide range of health benefits have been attributed to the modulation of various signalling pathways involved in the development of a particular disease. For example, the antitumour and cancer preventive properties of alpha-santalol have been shown to involve cell death induction through apoptosis and cell cycle arrest in various cancer models. A marked decrease in inflammatory markers have also been shown with alpha-santalol administration in skin tissue models. The current review is aimed at bringing the most recent advances of alpha-santalol against various disease-specific models and highlighting its associated mechanistic details.

Alpha-Santalol, a Component of Sandalwood Oil Inhibits Migration of Breast Cancer Cells by Targeting the ß-catenin Pathway.

BACKGROUND/AIM: Alpha-santalol, a terpenoid found in sandalwood oil has been shown to inhibit breast cancer cell growth in vitro by inducing apoptosis, but the mechanisms underlying the growth inhibitory effects of alpha-santalol are not fully understood. In this study, we demonstrate that α-santalol treatment targets Wnt/ß-catenin pathway to inhibit migration of cultured breast cancer cells. MATERIALS AND METHODS: Migration assays, immunoblotting and immunofluorescence were used to examine the mechanism of action of a-santalol in breast cancer cells. RESULTS: Exposure of MDA-MB 231 and MCF-7 cells to α-santalol resulted in a significant reduction in their migratory potential and wound healing ability. In addition, α-santalol affected the localization of ß-catenin from cytosol to nucleus in MDA-MB 231 cells. CONCLUSION: Alpha-santalol inhibited migration of breast cancer cells may be mediated, in part, by targeting Wnt//ß-catenin pathway. ß-catenin represents an important target of α-santalol's response for future pre-clinical studies.

Chemoprevention of Breast Cancer by Transdermal Delivery of α-Santalol through Breast Skin and Mammary Papilla (Nipple).

PURPOSE: Almost all breast cancers originate from epithelial cells lining the milk ducts in the breast. To this end, the study investigated the feasibility of localized transdermal delivery of α-santalol, a natural chemopreventive agent to the breast. METHODS: Different α-santalol formulations (cream, solution and microemulsion) were developed and the in vitro permeability was studied using excised animal (porcine and rat) and human breast skin/mammary papilla (nipple). The in vivo biodistribution and efficacy studies were conducted in female rats. A chemical carcinogenesis model of breast cancer was used for the efficacy studies. RESULTS: Phospholipid based α-santalol microemulsion showed the highest penetration through the nipple and breast skin. Delivery of α-santalol through the entire breast (breast skin and nipple) in vivo in rats resulted in significantly higher concentration in the mammary gland compared to transdermal delivery through the breast skin or nipple. There was no measurable α-santalol concentration in the blood. Transdermal delivery of α-santalol reduced the tumor incidence and tumor multiplicity. Furthermore, the tumor size was significantly reduced with α-santalol treatment. CONCLUSIONS: The findings from this study demonstrate the feasibility of localized transdermal delivery of α-santalol for chemoprevention of breast cancer.

Anticancer Effects of Sandalwood (Santalum album).

Effective management of tumorigenesis requires development of better anticancer agents with greater efficacy and fewer side-effects. Natural products are important sources for the development of chemotherapeutic agents and almost 60% of anticancer drugs are of natural origin. α-Santlol, a sesquiterpene isolated from Sandalwood, is known for a variety of therapeutic properties including anti-inflammatory, anti-oxidant, anti-viral and anti-bacterial activities. Cell line and animal studies reported chemopreventive effects of sandalwood oil and α-santalol without causing toxic side-effects. Our laboratory identified its anticancer effects in chemically-induced skin carcinogenesis in CD-1 and SENCAR mice, ultraviolet-B-induced skin carcinogenesis in SKH-1 mice and in vitro models of melanoma, non-melanoma, breast and prostate cancer. Its ability to induce cell-cycle arrest and apoptosis in cancer cells is its most reported anticancer mechanism of action. The present review discusses studies that support the anticancer effect and the mode of action of sandalwood oil and α-santalol in carcinogenesis.

Time and dose-response effects of honokiol on UVB-induced skin cancer development.

Honokiol has shown chemopreventive effects in chemically-induced and UVB-induced skin cancer in mice. In this investigation, we assessed the time-effects of a topical low dose of honokiol (30 µg), and then the effects of different honokiol doses (30, 45, and 60 µg) on a UVB-induced skin cancer model to find an optimal dose and time for desirable chemopreventive effects. UVB radiation (30 mJ/cm(2), 5 days/week for 25 or 27 weeks) was used to induce skin carcinogenesis in SKH-1 mice. For the time-response experiment 30 µg honokiol in acetone was applied topically to the animals before the UVB exposure (30 min, 1 h, and 2 h) and after the UVB exposure (immediately, 30 min, and 1 h). Control groups were treated with acetone. For the dose-response study, animals were treated topically with acetone or honokiol (30, 45, and 60 µg) one hour before the UVB exposure. In the time-response experiment, honokiol inhibited skin tumor multiplicity by 49-58% while reducing tumor volumes by 70-89%. In the dose-response study, honokiol (30, 45, and 60 µg) significantly decreased skin tumor multiplicity by 36-78% in a dose-dependent manner, while tumor area was reduced by 76-94%. Honokiol (60 µg) significantly reduced tumor incidence by 40% as compared to control group. Honokiol applied in very low doses (30 µg) either before or after UVB radiation shows chemopreventive effects. Honokiol (30, 45, and 60 µg) prevents UVB-induced skin cancer in a dose-dependent manner. Honokiol can be an effective chemopreventive agent against skin cancer.

α-Santalol, a derivative of sandalwood oil, induces apoptosis in human prostate cancer cells by causing caspase-3 activation.

The anticancer effects of α-santalol, a major component of sandalwood oil, have been reported against the development of certain cancers such as skin cancer both in vitro and in vivo. The primary objectives of the current study were to investigate the cancer preventive properties of α-santalol on human prostate cancer cells PC-3 (androgen independent and P-53 null) and LNCaP (androgen dependent and P-53 wild-type), and determine the possible mechanisms of its action. The effect of α-santalol on cell viability was determined by trypan blue dye exclusion assay. Apoptosis induction was confirmed by analysis of cytoplasmic histone-associated DNA fragmentation using both an apoptotic ELISA kit and a DAPI fluorescence assay. Caspase-3 activity was determined using caspase-3 (active) ELISA kit. PARP cleavage was analyzed using immunoblotting. α-Santalol at 25-75 µM decreased cell viability in both cell lines in a concentration and time dependent manner. Treatment of prostate cancer cells with α-santalol resulted in induction of apoptosis as evidenced by DNA fragmentation and nuclear staining of apoptotic cells by DAPI. α-Santalol treatment also resulted in activation of caspase-3 activity and PARP cleavage. The α-santalol-induced apoptotic cell death and activation of caspase-3 was significantly attenuated in the presence of pharmacological inhibitors of caspase-8 and caspase-9. In conclusion, the present study reveals the apoptotic effects of α-santalol in inhibiting the growth of human prostate cancer cells.

Skin cancer chemoprevention by α-santalol.

Alpha-santalol, a naturally occurring terpenoid, has been shown to have chemopreventive effects on both 7, 12-dimethylbenz(a)anthracene (DMBA)-initiated and 12-O- tetradecanoylphorbol-13-acetate (TPA)-promoted skin cancer development in CD-1 and SENCAR mice, and UVB-induced skin cancer developments in SKH-1 hairless mice in a concentration-dependent manner. Studies have demonstrated that α-santalol could be effective against skin carcinogenesis through both induction of apoptosis via caspase activation together with dissipation of mitochondria membrane potential and cytochrome c release in A431 cells, and inhibition of cell growth via induction of G2/M phase arrest in both A431 cells and melanoma UACC-62 cells by altering multiple cell cycle regulatory proteins and complexes. This review summarizes the chemopreventive effects and molecular mechanisms of α-santalol on skin cancer development in both animal models and skin cancer cell lines.

Chemopreventive effects of dietary canola oil on colon cancer development.

Fatty acid composition of dietary fat plays a vital role in colon tumor development in animal models. Fats containing ω-6 fatty acids (e.g., corn oil) enhanced and ω-3 fatty acids (e.g., flaxseed oil) reduced chemically induced colon tumor development in rats. The objective of the present investigation was to study the effects of dietary canola oil, a source of ω-3 fatty acid on azoxymethane-induced colon cancer development in Fischer rats and compare with dietary corn oil. Dietary canola oil significantly (P<0.05) decreased colonic tumor incidence and tumor multiplicity as compared to dietary corn oil in rats. Fatty acid analysis showed that corn oil group had higher levels of ω-6 fatty acid levels, whereas the canola oil groups exhibited higher levels of ω-3 fatty acids from the colon and serum samples of rats. For the mechanistic study, COX-2 expression in the colon samples from the canola oil group was significantly lower (P<0.05) as compared to the corn oil group. Taken together, dietary canola oil may be chemopreventive for colon tumor development in Fischer rats as compared to possibly by increasing ω-3 fatty acid levels and decreasing COX-2 levels.

The effect of ghee (clarified butter) on serum lipid levels and microsomal lipid peroxidation.

Ghee, also known as clarified butter, has been utilized for thousands of years in Ayurveda as a therapeutic agent. In ancient India, ghee was the preferred cooking oil. In the last several decades, ghee has been implicated in the increased prevalence of coronary artery disease (CAD) in Asian Indians due to its content of saturated fatty acids and cholesterol and, in heated ghee, cholesterol oxidation products. Our previous research on Sprague-Dawley outbred rats, which serve as a model for the general population, showed no effect of 5 and 10% ghee-supplemented diets on serum cholesterol and triglycerides. However, in Fischer inbred rats, which serve as a model for genetic predisposition to diseases, results of our previous research showed an increase in serum total cholesterol and triglyceride levels when fed a 10% ghee-supplemented diet. In the present study, we investigated the effect of 10% dietary ghee on microsomal lipid peroxidation, as well as serum lipid levels in Fischer inbred rats to assess the effect of ghee on free radical mediated processes that are implicated in many chronic diseases including cardiovascular disease. Results showed that 10% dietary ghee fed for 4 weeks did not have any significant effect on levels of serum total cholesterol, but did increase triglyceride levels in Fischer inbred rats. Ghee at a level of 10% in the diet did not increase liver microsomal lipid peroxidation or liver microsomal lipid peroxide levels. Animal studies have demonstrated many beneficial effects of ghee, including dose-dependent decreases in serum total cholesterol, low density lipoprotein (LDL), very low density lipoprotein (VLDL), and triglycerides; decreased liver total cholesterol, triglycerides, and cholesterol esters; and a lower level of nonenzymatic-induced lipid peroxidation in liver homogenate. Similar results were seen with heated (oxidized) ghee which contains cholesterol oxidation products. A preliminary clinical study showed that high doses of medicated ghee decreased serum cholesterol, triglycerides, phospholipids, and cholesterol esters in psoriasis patients. A study on a rural population in India revealed a significantly lower prevalence of coronary heart disease in men who consumed higher amounts of ghee. Research on Maharishi Amrit Kalash-4 (MAK-4), an Ayurvedic herbal mixture containing ghee, showed no effect on levels of serum cholesterol, high density lipoprotein (HDL), LDL, or triglycerides in hyperlipidemic patients who ingested MAK-4 for 18 weeks. MAK-4 inhibited the oxidation of LDL in these patients. The data available in the literature do not support a conclusion of harmful effects of the moderate consumption of ghee in the general population. Factors that may be involved in the rise of CAD in Asian Indians include the increased use of vanaspati (vegetable ghee) which contains 40% trans fatty acids, psychosocial stress, insulin resistance, and altered dietary patterns. Research findings in the literature support the beneficial effects of ghee outlined in the ancient Ayurvedic texts and the therapeutic use of ghee for thousands of years in the Ayurvedic system of medicine.

Effects of dietary flaxseed on intestinal tumorigenesis in Apc(Min) mouse.

Dietary flaxseed has been shown to prevent azoxymethane (AOM)-induced colorectal cancers in male Fisher rats. The present study was designed to investigate the chemopreventive effects of dietary flaxseed on the development of intestinal tumors in Apc(Min) mice. Apc(Min) mice were divided into five different groups, fed with control (AIN-93M meal), corn meal, flaxseed meal, corn oil, and flaxseed oil supplemented diets. Results showed that dietary flaxseed significantly decreased (P < 0.05) tumor multiplicity and size in the small intestine and colon as compared to control, corn-treated groups. Intestine, colon, and serum samples of corn-treated groups showed higher levels of omega -6 fatty acids, whereas the flaxseed treated groups exhibited higher levels of omega -3 fatty acids. Lignans were detected in the serum, intestine, and colon samples for flaxseed meal group. COX-1 and COX-2 expression in the colon samples from the flaxseed meal group were significantly lower (P < 0.05) as compared to the corn meal group. Dietary flaxseed may be chemopreventive for intestinal tumor development in Apc(Min) mice possibly by increasing omega -3 fatty acid levels, lignans, and decreasing COX-1 and COX-2 levels.

Chemopreventive effects of dietary flaxseed on colon tumor development.

Fatty acid composition of dietary fat plays a vital role in colon tumor development in animal models. Fats containing omega-6 fatty acids (e.g., corn oil) enhanced and omega-3 fatty acids (e.g., flaxseed oil) reduced chemically induced colon tumor development in rats. Lignans have also been shown to prevent colon tumor development in experimental animals. The objective of this investigation is to study the effects of dietary flaxseed meal, a source of both omega-3 fatty acid and lignans, on colon tumor development and compare them with the effects of dietary corn meal. Male Fischer rats, two groups of 24 each, were assigned to the AIN-93M diet supplemented with either 15% corn meal or 15% flaxseed meal, respectively. Carcinogenesis was initiated with subcutaneous injections of azoxymethane (15 mg/kg) once a week for 3 consecutive wk. After 35 wk of initiation, rats were anesthetized with ether. Blood was collected by cardiac puncture, and rats were sacrificed. The gastrointestinal tract was isolated. The site, size, and number of tumors were recorded. The fatty acid analysis of the collected serum and colon samples was performed. Expression of cyclooxygenase (COX)-1 and COX-2 was performed by Western blot method. Lignan levels in serum and colon samples were assayed. Colon tumor incidence, multiplicity, and size were found to be 82.6% and 29.4%; 1.3 and 0.3; and 44.4 and 5.3 mm(2) in corn and flaxseed meal groups, respectively. Colon and serum samples of the corn meal group showed higher levels of omega-6 fatty acid levels whereas the flaxseed meal group exhibited higher levels of omega-3 fatty acids. COX-1 and COX-2 expression in the flaxseed group was significantly lower (P < 0.05) as compared to the corn group. Dietary flaxseed meal containing high levels of omega-3 fatty acids and lignans is effective in preventing colon tumor development when compared with dietary corn meal possibly by increasing omega-3 fatty acid levels and decreasing COX-1 and COX-2 levels.

Chemopreventive effects of alpha-santalol on ultraviolet B radiation-induced skin tumor development in SKH-1 hairless mice.

Recent studies from our laboratory have shown the chemopreventive effects of alpha-santalol against 7,12-dimethylbenzanthracene (DMBA) initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA) promoted skin tumor development in mice. The objective of the present investigation was to study the effects of alpha-santalol on ultraviolet B (UVB) radiation-induced skin tumor development and UVB-caused increase in epidermal ornithine decarboxylase (ODC) activity in female hairless SKH-1 mice. For the tumor studies, 180 mice were divided into three groups of 60 mice each, and each group was divided into two subgroups of 30 mice. The first subgroup served as control and was treated topically on the dorsal skin with acetone. The second subgroup served as experimental and was treated topically on the dorsal skin with alpha-santalol (5%, w/v in acetone). The tumorigenesis in the first group was initiated with UVB radiation and promoted with TPA; in the second group it was initiated with DMBA and promoted with UVB radiation; and in the third group it was both initiated and promoted with UVB radiation. In each case, the study was terminated at 30 weeks. Topical application of alpha-santalol significantly (P<0.05) decreased tumor incidence and multiplicity in all the three protocols, suggesting its chemopreventive efficacy against UVB radiation-caused tumor initiation, tumor promotion and complete carcinogenesis. In a short-term biochemical study, topical application of alpha-santalol also significantly (P<0.05) inhibited UVB-induced epidermal ODC activity. Together, for the first time, our findings suggest that alpha-santalol could be a potential chemopreventive agent against UVB-induced skin tumor development and, therefore, warrants further investigations.

Antioxidant and protective effects of Amrit Nectar tablets on adriamycin- and cisplatin-induced toxicities.

OBJECTIVES: Maharishi herbal food supplements have been shown to inhibit the growth of mammary tumors and reduce free radical-mediated injuries. The purpose of this investigation is to evaluate the effects of aqueous and alcoholic extracts of Amrit Nectar tablets on rat liver microsomal lipid peroxidation and compare to other antioxidants. The protective effects of dietary Amrit Nectar tablets (MA-7; containing 38 herbs) on cisplatin-induced changes in glutathione (GSH) and glutathione-S-transferase (GST) activity in rat liver and kidney, and Adriamycin (Pharmacia S.p.A, Milan, Italy)-induced mortalities in mice were also investigated. RESULTS: Both aqueous and alcoholic extracts of MA-7 were more potent than other antioxidants tested under our experimental conditions. Adriamycin (15 mg/kg, intraperitoneally) caused 60% mortality during the period of 4 weeks in CDF1 mice. Dietary MA-7 (0.7%) treatment decreased the mortality to 20%. Dietary MA-7 (0.7%) supplementation with cisplatin treatment reversed the effects of cisplatin on liver and kidney GSH and GST activity. CONCLUSIONS: These results indicate that MA-7 is a powerful antioxidant. MA-7 supplementation with Adriamycin and cisplatin treatment may protect against their toxicities.

Chemopreventive effects of dietary flaxseed oil on colon tumor development.

Fatty acid composition of dietary fat, primarily the levels of omega-3 and omega-6 polyunsaturated fatty acids, has shown profound effect on colon tumor development in animal studies. Fats containing omega-6 fatty acids (for example, corn oil) enhanced and omega-3 fatty acids (for example, fish oil and mustard oil) reduced chemically induced colon tumors in rats. The purpose of this study was to investigate the effects of dietary flaxseed oil (containing alpha-linolenic acid, an omega-3 polyunsaturated fatty acid) on azoxymethane-induced colon tumor in rats and how it compared with the dietary corn oil-treated group. Male Fischer rats, separated into 2 groups of 30, were assigned to the AIN-93M diet, which was supplemented with either 15% corn oil or 15% flaxseed oil. Carcinogenesis was initiated with subcutaneous injections of azoxymethane (15 mg/kg) once a week for three consecutive weeks. Thirty-five weeks after initiation, the rats were sacrificed under ether anesthesia. Blood was collected by cardiac puncture. The gastrointestinal tract was isolated and flushed with ice-cold normal saline. The site, size, and number of tumors were recorded. The incidence and multiplicity of the tumors in the colon were determined. The fatty acid composition in the serum, colon, and tumors was estimated by using gas chromatography-flame ionization detection. Colon tumor incidence was found to be 100% and 54%, whereas multiplicity was found to be 3.1 and 0.7 tumors per rat in corn oil- and flaxseed oil-treated groups, respectively. Tumor size was significantly larger in the corn oil-treated group than in the flaxseed oil group. Colon and serum samples of the corn oil group showed an increase in the omega-6 fatty acid levels, whereas the flaxseed oil group exhibited an increase in the omega-3 fatty acid levels. The results indicate that dietary flaxseed oil, containing high levels of omega-3 fatty acids, is effective in preventing colon tumor development when compared with dietary corn oil containing omega-6 fatty acids in rats.

Skin cancer chemopreventive agent, {alpha}-santalol, induces apoptotic death of human epidermoid carcinoma A431 cells via caspase activation together with dissipation of mitochondrial membrane potential and cytochrome c release.

alpha-Santalol, an active component of sandalwood oil, has been studied in detail in recent years for its skin cancer preventive efficacy in murine models of skin carcinogenesis; however, the mechanism of its efficacy is not defined. Two major biological events responsible for the clonal expansion of transformed/initiated cells into tumors are uncontrolled growth and loss of apoptotic death. Accordingly, in the present study, employing human epidermoid carcinoma A431 cells, we assessed whether alpha-santalol causes cell growth inhibition and/or cell death by apoptosis. Treatment of cells with alpha-santalol at concentrations of 25-75 microM resulted in a concentration- and a time-dependent decrease in cell number, which was largely due to cell death. Fluorescence-activated cell sorting analysis of Annexin V/propidium iodide (PI) stained cells revealed that alpha-santalol induces a strong apoptosis as early as 3 h post-treatment, which increases further in a concentration- and a time-dependent manner up to 12 h. Mechanistic studies showed an involvement of caspase-3 activation and poly(ADP-ribose) polymerase cleavage through activation of upstream caspase-8 and -9. Further, the treatment of cells with alpha-santalol also led to disruption of the mitochondrial membrane potential and cytochrome c release into the cytosol, thereby implicating the involvement of the mitochondrial pathway. Pre-treatment of cells with caspase-8 or -9 inhibitor, pan caspase inhibitor or cycloheximide totally blocked alpha-santalol-caused caspase-3 activity and cleavage, but only partially reversed apoptotic cell death. This suggests involvement of both caspase-dependent and -independent pathways, at least under caspase inhibiting conditions, in alpha-santalol-caused apoptosis. Together, this study for the first time identifies the apoptotic effect of alpha-santalol, and defines the mechanism of apoptotic cascade activated by this agent in A431 cells, which might be contributing to its overall cancer preventive efficacy in mouse skin cancer models.

Chemopreventive effects of pomegranate seed oil on skin tumor development in CD1 mice.

Pomegranate seed oil was investigated for possible skin cancer chemopreventive efficacy in mice. In the main experiment, two groups consisting each of 30, 4-5-week-old, female CD(1) mice were used. Both groups had skin cancer initiated with an initial topical exposure of 7,12-dimethylbenzanthracene and with biweekly promotion using 12-O-tetradecanoylphorbol 13-acetate (TPA). The experimental group was pretreated with 5% pomegranate seed oil prior to each TPA application. Tumor incidence, the number of mice containing at least one tumor, was 100% and 93%, and multiplicity, the average number of tumors per mouse, was 20.8 and 16.3 per mouse after 20 weeks of promotion in the control and pomegranate seed oil-treated groups, respectively (P <.05). In a second experiment, two groups each consisting of three CD(1) mice were used to assess the effect of pomegranate seed oil on TPA-stimulated ornithine decarboxylase (ODC) activity, an important event in skin cancer promotion. Each group received a single topical application of TPA, with the experimental group receiving a topical treatment 1 h prior with 5% pomegranate seed oil. The mice were killed 5 h later, and ODC activity was assessed by radiometric method. The experimental group showed a 17% reduction in ODC activity. Pomegranate seed oil (5%) significantly decreased (P <.05) tumor incidence, multiplicity, and TPA-induced ODC activity. Overall, the results highlight the potential of pomegranate seed oil as a safe and effective chemopreventive agent against skin cancer.

Chemopreventive effects of dietary mustard oil on colon tumor development.

Fatty acid composition of dietary fat is one of the detrimental factors in colon cancer development. Fats containing omega 6-polyunsaturated fatty acids (e.g. corn oil) enhance and omega 3-polyunsaturated fatty acids (e.g. fish oil) reduce chemically-induced colon cancer in animal studies. The purpose of this study is to investigate the effects of dietary mustard oil (containing omega 3-polyunsaturated fatty acid) on azoxymethane-induced colon cancer in rats and compare with corn and fish oil treated groups. Colon tumor incidence and multiplicity were found to be 90, 75, and 50% and 1.7, 0.8, and 0.4 tumors/rat in corn, fish and mustard oil treated groups respectively. Omega-3 polyunsaturated fatty acid levels were highest in serum and colon microsomal fractions of the fish oil group followed by the mustard oil group. Corn oil group had the highest level of omega 6-polyunsaturated fatty acid levels in serum and colon microsomal fractions. The results indicate that dietary mustard oil is more effective in preventing colon cancer in rats than dietary fish oil.

Chemopreventive effects of alpha-santalol on skin tumor development in CD-1 and SENCAR mice.

Studies from our laboratory have indicated skin cancer chemopreventive effectsof sandalwood oil in CD-1 mice. The purpose of this investigation was to study the skin cancer chemopreventive effects of alpha-santalol, a principal component of sandalwood oil in CD-1 and SENCAR mice. alpha-Santalol was isolated from sandalwood oil by distillation under vacuum and characterized by nuclear magnetic resonance and gas chromatography-mass spectrometry. Chemopreventive effects of alpha-santalol were determined during initiation and promotion phase in female CD-1 and SENCAR mice. Carcinogenesis was initiated with 7,12-dimethylbenz(a)anthracene and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA). The effects of alpha-santalol treatment on TPA-induced epidermal ornithine decarboxylase (ODC) activity and (3)H-thymidine incorporation in epidermal DNA of CD-1 and SENCAR mice were also investigated. alpha-Santalol treatment during promotion phase delayed the papilloma development by 2 weeks in both CD-1 and SENCAR strains of mice. alpha-Santalol treatment during promotion phase significantly (P < 0.05) decreased the papilloma incidence and multiplicity when compared with control and treatment during initiation phase during 20 weeks of promotion in both CD-1 and SENCAR strains of mice. alpha-Santalol treatment resulted in a significant (P < 0.05) inhibition in TPA-induced ODC activity and incorporation of (3)H-thymidine in DNA in the epidermis of both strains of mice. alpha-Santalol significantly prevents papilloma development during promotion phase of 7,12-dimethylbenz(a)anthracene-TPA carcinogenesis protocol in both CD-1 and SENCAR mice, possibly by inhibiting TPA-induced ODC activity and DNA synthesis. alpha-Santalol could be an effective chemopreventive agent for skin cancer. Additional experimental and clinical studies are needed to investigate the chemopreventive effect of alpha-santalol in skin cancer.