Chemopreventive potential of β-Sitosterol in experimental colon cancer model - an In vitro and In vivo study

Abstract

BackgroundAsclepias curassavica Linn. is a traditional medicinal plant used by tribal people in the western ghats, India, to treat piles, gonorrhoea, roundworm infestation and abdominal tumours. We have determined the protective effect of β-sitosterol isolated from A. curassavica in colon cancer, using in vitro and in vivo models.MethodsThe active molecule was isolated, based upon bioassay guided fractionation, and identified as β-sitosterol on spectral evidence. The ability to induce apoptosis was determined by its in vitro antiradical activity, cytotoxic studies using human colon adenocarcinoma and normal monkey kidney cell lines, and the expression of β-catenin and proliferating cell nuclear antigen (PCNA) in human colon cancer cell lines (COLO 320 DM). The chemopreventive potential of β-sitosterol in colon carcinogenesis was assessed by injecting 1,2-dimethylhydrazine (DMH, 20 mg/kg b.w.) into male Wistar rats and supplementing this with β-sitosterol throughout the experimental period of 16 weeks at 5, 10, and 20 mg/kg b.w.Resultsβ-sitosterol induced significant dose-dependent growth inhibition of COLO 320 DM cells (IC50 266.2 μM), induced apoptosis by scavenging reactive oxygen species, and suppressed the expression of β-catenin and PCNA antigens in human colon cancer cells. β-sitosterol supplementation reduced the number of aberrant crypt and crypt multiplicity in DMH-initiated rats in a dose-dependent manner with no toxic effects.ConclusionWe found doses of 10-20 mg/kg b.w. β-sitosterol to be effective for future in vivo studies. β-sitosterol had chemopreventive potential by virtue of its radical quenching ability in vitro, with minimal toxicity to normal cells. It also attenuated β-catenin and PCNA expression, making it a potential anticancer drug for colon carcinogenesis.

Comparative Circadian Metabolomics Reveal Differential Effects of Nutritional Challenge in the Serum and Liver

“…Other examples of metabolites that we have found altered and are known to be associated with human diseases are ␤-sitosterol, hydroxyproline, N 1 -methyguanosine, cytidine, indoxyl sulfate, pyruvate, and creatinine, all of which have been reported to be involved in cancer (85)(86)(87)(88)(89)(90)(91)(92)(93) (Fig. 9, A, B, D, and E).…”

Jamun (<i>Syzygium cumini </i>(L.)): A Review of Its Food and Medicinal Uses

“…Additionally, recent observations also suggest that ellagitannin, a constituent of Jamun and its colonic 3 Gallic acid 1) Inhibits the TPA-induced inductions of epidermal ornithine decarboxylase activity, hydroperoxide production and DNA synthesis, and also inhibit the promotion of skin papillomas and carcinomas in the two-step initiationpromotion protocol [79]; 2) Administering (0.3% to 1%) for twenty consecutive weeks from four weeks of age to the male TRAMP mice (a transgenic mice develops prostate tumor) caused a decrease tumors with decreasing the proliferative index with a concomitant increase in the apoptotic cells which were due to decrease in the expression of Cdc2, Cdk2, Cdk4, Cdk6, cyclin B1 and E [83]. [91,92], and mitogen-activated protein kinase (MEK) [93] and inhibitor of of neoplastic cell transformation and MEK1 [94]; 2) Prevents TPA-induced transformation, PKC activation, and c-jun expression in mouse fibroblast cells [95]; 3) Suppresses UVB-induced skin cancer by targeting Fyn in JB6 cells [96]. Inhibits Akt survival signaling and induces Bad-mediated apoptosis in immortalized human keratinocytes (HaCaT cells) [97]; 4) Inhibits matrix metalloproteinase 2 protein expression and enzyme activity in colorectal carcinoma cells [98] and also down-regulates phorbol ester-induced cyclooxygenase-2 expression in mouse epidermal cells by blocking activation of nuclear factor kappa B [94]; 5) Inhibits polycyclic aromatic hydrocarbon-DNA adduct formation in epidermis and lungs of SENCAR mice [99].…”

“…[91,92], and mitogen-activated protein kinase (MEK) [93] and inhibitor of of neoplastic cell transformation and MEK1 [94]; 2) Prevents TPA-induced transformation, PKC activation, and c-jun expression in mouse fibroblast cells [95]; 3) Suppresses UVB-induced skin cancer by targeting Fyn in JB6 cells [96]. Inhibits Akt survival signaling and induces Bad-mediated apoptosis in immortalized human keratinocytes (HaCaT cells) [97]; 4) Inhibits matrix metalloproteinase 2 protein expression and enzyme activity in colorectal carcinoma cells [98] and also down-regulates phorbol ester-induced cyclooxygenase-2 expression in mouse epidermal cells by blocking activation of nuclear factor kappa B [94]; 5) Inhibits polycyclic aromatic hydrocarbon-DNA adduct formation in epidermis and lungs of SENCAR mice [99]. metabolite, urolithin A inhibit want signaling crucial in the process of colon carcinogenesis [106].…”

Terpenoids and Sterols from Hoya multiflora Blume

“…β-Amyrin (1c) and α-amyrin (1b) were reported to possess antiinflammatory (Recio et al, 1995;Madeiros et al, 2007;Okoye et al, 2014) and analgesic (Otuki et al, 2005;Soldi et al, 2008) properties. β-Amyrin showed antifungal activity against A. rabiei with an MIC value of 0.0156 mg/mL (Jabeen et al, 2011)., α-Amyrin was proposed as a possible biomarker for the fungal resistance of grape-vine leaves (Vitis vinifera) (Batovska et al, 2008). The mixture of 1b and 1c effectively reduced the elevated plasma glucose levels during the oral glucose tolerance test (OGTT).…”