Chemopreventive Activity of 80% Methanol Leaf Extract of Vernonia auriculifera Hiern (Asteraceae) Against Dimethylhydrazine-Induced Colorectal Carcinogenesis in Rats

Yohannes Tsegyie Wondmkun,1 Ephrem Engidawork,1 Wajana Lako Labisso,2 Anteneh Belete,3 Solomon Tesfaye,1 Yonas Girma Shumiye2 1Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, Addis Ababa University, Addis Ababa, Ethiopia; 2Department of Pathology, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia; 3Department of Pharmaceutics and Social Pharmacy, School of Pharmacy, Addis Ababa University, Addis Ababa, EthiopiaCorrespondence: Ephrem Engidawork; Yohannes Tsegyie, Email [email protected]; [email protected]; [email protected]: Vernonia auriculifera Hiern (Asteraceae) is among Ethiopian herbal medicines that are traditionally used to treat skin and gastrointestinal cancers. In this study, the chemopreventive potential of Vernonia auriculifera leaf extract in dimethylhydrazine (DMH)-induced colorectal carcinogenesis in rats was investigated.Methods: Rats were assigned to nine groups (normal, positive, and negative control groups, and three pre- and three post-initiation groups). Except for the normal control group (administered with 1 mL/100 g distilled water), the remaining eight groups were given DMH (20 mg/kg) intraperitoneally (ip) for 15 consecutive weeks to induce colorectal tumours. The extract was given orally to the pre-initiation and post-initiation groups at doses of 100, 200, and 400 mg/kg before and after the induction of cancer, respectively. The positive control group was treated with aspirin (60 mg/kg/day) orally for the whole experimental period. Parameters including body weight, average tumour number, size, progression, incidence, total cholesterol, serum total protein, and triglyceride levels were determined. The cytotoxic activity of the extract in Caco-2 cells was evaluated using the MTT assay, and the antioxidant activity of the extract was also assessed using 2.2-diphenyl-1-picrylhydrazine (DPPH) and reducing power methods. Moreover, total phenol and flavonoid contents were determined using appropriate methods.Results: Rats treated with the extract showed a lower incidence of up to 50% in the pre-initiation higher dose, average number (p< 0.05),and size (p< 0.05) of tumours compared to untreated rats. It also inhibited colorectal cancer-associated increases in serum total cholesterol and triglycerides. The extract’s IC50 value in the MTT assay was found to be higher than 200 μg/mL. The extract had an IC50 of 74.88 ± 0.86 μg/mL and 84.69 ± 2.02 μg/mL in the reducing power and DPPH assays, respectively. Total flavonoid and phenol contents were 14.51 ± 0.41 mg quercetin acid equivalent/gm and 47.37 ± 0.72 mg gallic acid equivalent/gm of the crude extract, respectively.Conclusion: The findings collectively indicated that the leaves of V. auriculifera possess chemopreventive activity, probably mediated through antioxidant mechanisms, which supports the traditional claim.Keywords: antioxidant, cytotoxicity, colorectal cancer, pre-initiation, post-initiation, Vernonia auriculifer

High Expression of long non-coding RNA PVT1 predicts metastasis in Han and Uygur Patients with Gastric Cancer in Xinjiang, China

Abstract To analyze the level and diagnostic value of plasmacytoma variant translocation 1 (PVT1) in gastric cancer (GC) of Han and Uygur in Xinjiang, China, we collected 42 GC and 47 normal gastric tissues and performed tissue microarray. In situ hybridization was used to detect PVT1, while immunohistochemistry was used to analyze c-myc. The relationship between PVT1, c-myc and clinical pathological features was investigated. We then analyzed the expression of PVT1 in six GC cell lines. RNA interference was used to silence PVT1 in BGC823 and AGS cells. c-myc was detected by western blotting after silencing PVT1, while proliferation, invasion and migration ability were also analyzed. We found that PVT1 and c-myc were highly expressed in both Han and Uygur GC tissues. In Han GC, PVT1 was correlated with lymph node metastasis and primary tumor site. In Uygur GC, both PVT1 and c-myc were correlated with lymph node metastasis and clinical staging. PVT1 was positively correlated with c-myc. BGC823 and AGS cells exhibited high levels of PVT1. When PVT1 expression was silenced, the expression of c-myc decreased, while migration and invasion ability were also decreased in cells. PVT1 could therefore be a potential biomarker to predict the metastatic tendency of GC in both Han and Uygur patients