Orientin Induces G0/G1 Cell Cycle Arrest and Mitochondria Mediated Intrinsic Apoptosis in Human Colorectal Carcinoma HT29 Cells.

Colorectal carcinoma is one of the utmost diagnosed cancer with a steep increase in mortality rate. The incidence has been increasing in developing countries like India due to a westernization life style. Flavonoids have been explored widely for its various pharmacological activity including antitumor activity. Orientin, an analogue of luteolin (citrus flavonoid) isolated from rooibos and tulsi leaves is also expected to deliver significant antitumor activity similar to that of luteolin. The present study anticipates exploring the antitumor activity of orientin against colorectal carcinoma cells (HT29). Orientin exhibited remarkable cytotoxicity and antiproliferative activity against HT29 cells, which is clearly evident from tetrazolium based cytotoxicity and lactate dehydrogenase release assays. Orientin induce G0/G1 cell cycle arrest and regulates cyclin and cyclin-dependent protein kinases in order to prevent the entry of the cell cycle to the S phase. Annexin V-FITC (V-Fluorescein Isothiocyanate) dual staining reveals the apoptotic induction ability of orientin. The Bcl-2 family proteins along with the inhibitor of apoptotic proteins were regulated and the tumor suppressor p-53 expression have been decreased. In conclusion, our results proposed that orientin could be a potent chemotherapeutic agent against colorectal cancer after ascertaining their molecular mechanisms.

Orientin mitigates 1, 2-dimethylhydrazine induced lipid peroxidation, antioxidant and biotransforming bacterial enzyme alterations in experimental rats.

BACKGROUND: Colorectal cancer (CRC) is the second most diagnosed cancer often identified during the later stages of carcinogenesis. Orientin, a C-glycoside of luteolin, is well known for its versatile therapeutic action toward oxidative stress-induced cellular response may exert chemoprevention against CRC. MATERIALS AND METHODS: In our study, we investigated the modulatory effect of orientin on lipid peroxidation, antioxidant defense, and biotransforming bacterial enzymes in 1, 2-dimethylhydrazine (DMH)-induced male albino Wistar rats in a dose-dependent manner. Animals were induced with DMH (20 mg/kg b.wt) for 15 weeks and administered with orientin in three different doses (5 mg/kg, 10 mg/kg, and 20 mg/kg b. wt) daily under distinct phases (initiation, postinitiation, and the entire) for a total treatment period of 30 weeks. RESULTS: Orientin reinstates the alterations induced by DMH on lipid peroxidation and enzymatic antioxidants through its rich-free radical scavenging properties. In addition, orientin curtails the DMH-induced augmentation of biotransforming bacterial enzymes to inhibit the colon cancer progression. Overall, experimental findings suggest that orientin significantly inhibits the DMH induced colon cancer in all the three different doses, however, maximum inhibition was observed on supplementation of 10 mg/kg b.wt for the entire period of the study. CONCLUSION: Hence, the intraperitoneal administration of 10 mg/kg b.wt orientin for the entire period is recommended for further molecular investigation to elucidate the precise mechanism of inhibition and so orientin can be used as a novel chemotherapeutic agent for CRC.

Orientin, a flavanoid, mitigates 1, 2 dimethylhydrazine-induced colorectal lesions in Wistar rats fed a high-fat diet.

Orientin, a c- glycosyl flavonoid found copiously in roobios tea and various medicinal plants is well known for its antioxidant, anti-inflammatory, and antitumor effects. The present study aims to investigate the anti-cancer efficacy of orientin on 1,2 dimethyl hydrazine induced colonic aberrant crypt foci (ACF) and cell proliferation in Wistar rats. Rats were randomly divided into six groups and fed with high fat diet. Group 1 left as untreated control. Group 2 administered with DMH (20 mg/kg body weight) for initial 4 weeks and left untreated. Group 3 received orientin (10 mg/kg body weight) alone for the entire period. Group 4 received orientin along with DMH for initial 4 weeks and left untreated; Group 5 administered DMH for initial 4 weeks and treated with orientin for remaining 12 weeks; Group 6 administered DMH and treated with orientin throughout the entire period. Our preclinical findings suggest that the administration of orientin decreases the occurrence of DMH induced colonic polyps and aberrant crypt foci, augments antioxidant defense and altered the activities of drug metabolizing phase I and phase II enzymes in colonic and hepatic tissues and thereby ensuring the detoxification of carcinogen. Furthermore, orientin attenuates the aberrant crypt foci formation and reinstates the DMH induced cell proliferation, as evident from the AgNORs staining of colonic tissues of experimental rats. Thus, our study emphasizes that orientin may prevent DMH induced precancerous lesions and proven to be a potent antioxidant and antiproliferative agent.

Orientin, a C-glycosyl dietary flavone, suppresses colonic cell proliferation and mitigates NF-κB mediated inflammatory response in 1,2-dimethylhydrazine induced colorectal carcinogenesis.

Orientin, a C-glycosyl dietary flavone profusely found in rooibos tea and passion fruit have gained much attention owing to their multiple pharmacological potentials. The present study intends to investigate the anti-proliferative and anti-inflammatory efficacy of Orientin in 1,2-dimethyl hydrazine (DMH) induced colorectal cancer (CRC) in rats. Animals were arbitrarily segmented into six groups and fed with high-fat diet. Group 1 served as control. Group 2 received weekly subcutaneous injections of DMH (20 mg/kg b.w.), for first 15 weeks. Group 3 administered with Orientin (10 mg/kg b.w., i.p.) whereas Groups 4-6 treated with Orientin in three phases, namely initiation (along with DMH), post-initiation (post-DMH injection) and entire period. Orientin ameliorates tumor marker levels significantly (p < 0.05) and reinstates the histological changes induced by DMH. The proliferative markers (PCNA and Ki67) were observed to be suppressed significantly (p < 0.05) in Orientin treated rats. Orientin abrogates (p < 0.05) the inflammatory mast cells and diminishes the expression of pro-inflammatory NF-κB and cytokines (TNF-α and IL-6). It also down-regulates over expression of inflammatory inducible enzymes (iNOS and COX-2) significantly (p < 0.05) and further substantiated by GLIDE XP and QPLD studies. Overall results promptly elucidate the anti-proliferative and anti-inflammatory efficacy of Orientin against CRC. Orientin can be developed as a promising chemotherapeutic agent, on further validation of other molecular mechanisms.