Ginger extract adjuvant to doxorubicin in mammary carcinoma: study of some molecular mechanisms.

PURPOSE: The present study aimed to investigate the molecular mechanisms underlying the anticancer properties of ginger extract (GE) in mice bearing solid Ehrlich carcinoma (SEC) and to evaluate the use of GE in combination with doxorubicin (DOX) as a complementary therapy against SEC. METHODS: SEC was induced in 60 female mice. Mice were divided into four equal groups: SEC, GE, DOX and GE + DOX. GE (100 mg/kg orally day after day) and DOX (4 mg/kg i.p. for 4 cycles every 5 days) were given to mice starting on day 12 of inoculation. On the 28th day, blood samples were collected, mice were scarified, tumor volume was measured, and tumor tissues were excised. RESULTS: The anti-cancer effect of GE was mediated by activation of adenosine monophosphate protein kinase (AMPK) and down-regulation of cyclin D1 gene expression. GE also showed pro-apoptotic properties as evidenced by elevation of the P53 and suppression of nuclear factor-kappa B (NF-κB) content in tumor tissue. Co-administration of GE alongside DOX markedly increased survival rate, decreased tumor volume, and increased the level of phosphorylated AMPK (PAMPK) and improved related pathways compared to DOX group. In addition, the histopathological results demonstrated enhanced apoptosis and absence of multinucleated cells in tumor tissue of GE + DOX group. CONCLUSION: AMPK pathway and cyclin D1 gene expression could be a molecular therapeutic target for the anticancer effect of GE in mice bearing SEC. Combining GE and DOX revealed a greater efficacy as anticancer therapeutic regimen.

Chemopreventive effect of omega-3 polyunsaturated fatty acids and atorvastatin in rats with bladder cancer.

Bladder cancer remains a huge concern for the medical community because of its incidence and prevalence rates, as well as high percentage of recurrence and progression. Omega-3 polyunsaturated fatty acids and atorvastatin proved anti-inflammatory effects through peroxisome proliferator-activated receptor gamma mechanism. However, their chemopreventive effect still remained to be examined and clarified. In this study, bladder cancer was induced in rats by the chemical carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine. Omega-3 polyunsaturated fatty acids (docosahexaenoic acid and eicosapentaenoic acid: 2:3 w/w; 1200 mg/kg) and/or atorvastatin (6 mg/kg) were given orally daily to rats for eight consecutive weeks concomitantly with N-butyl-N-(4-hydroxybutyl)nitrosamine and continued for further 4 weeks after cessation of N-butyl-N-(4-hydroxybutyl)nitrosamine administration. The histopathological examination of rat bladder revealed the presence of tumors and the absence of apoptotic bodies in sections from N-butyl-N-(4-hydroxybutyl)nitrosamine group, while tumors were absent and apoptotic bodies were clearly observed in sections from rat groups treated with omega-3 polyunsaturated fatty acids, atorvastatin, or both drugs. The study of the molecular mechanisms illustrated downregulation of COX-2 and P53 (mutant) genes and suppression of transforming growth factor beta-1 and the lipid peroxidation product malondialdehyde in serum of rats of the three treated groups. This chemopreventive effect was confirmed by and associated with lower level of bladder tumor antigen in urine. However, the combined treatment with both drugs exhibited the major protective effect and nearly corrected the dyslipidemia that has been induced by N-butyl-N-(4-hydroxybutyl)nitrosamine. Collectively, omega-3 polyunsaturated fatty acids and atorvastatin, besides having anti-inflammatory properties, proved a chemopreventive effect against bladder cancer, which nominates them to be used as adjuvant therapy with other chemotherapeutics.

Effect of Pomegranate Hull Extract on Liver Neoplastic Changes in Rats: More than an Antioxidant.

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer-related mortality worldwide. The current work was designed to elucidate the molecular mechanisms underlying the antitumorigenic effect of pomegranate hull extract (PHE) in livers of rats exposed to the hepatocarcinogen diethyl nitrosamine (DENA) with emphasis on oxidative stress, proliferation, and apoptosis. Male albino rats were divided into three groups: normal control, DENA group, and PHE group. PHE was given to rats orally 3 times weekly for 10 wk, 4 wk before and 6 wk after DENA (200 mg/kg, single i.p. dose). The results indicated a prophylactic effect of PHE against neoplastic changes in the liver, which was evidenced by the decrease of tumor size, liver index, and the anti-apoptotic protein Bcl-2; and the increase of glutathione. PHE group also showed decreased expression of liver cyclin D1 and ß-catenin genes compared with DENA group. It is proved that PHE has antitumorigenic effect and could be a candidate for anticancer drugs.

Gastroprotective effect of garlic in indomethacin induced gastric ulcer in rats.

OBJECTIVE: Garlic, in its natural plant state, has a great history in ancient medicine as a remedy for many diseases. In our study, the gastroprotective effect of aged garlic extract (AGE) and the possible underlying mechanisms were investigated in an experimental model of indomethacin-induced gastric ulcer. METHODS: Male Wistar rats were divided into four groups: (normal control, n = 20), ulcer control (indomethacin group, n = 20), (omeprazole group, n = 30) and (garlic group, n = 20). Each dose of garlic and omeprazole was given to rats orally daily for 10 consecutive days before induction of ulcer by indomethacin. Indomethacin was given as a single oral dose (100 mg/kg). Four hours later after indomethacin treatment, the rats were sacrificed and gastric tissue was obtained for histopathological examination, calculation of ulcer index and measurement of oxidative stress markers as well as gastroprotective mediators. RESULTS: The results showed that indomethacin induced gastric ulcer (ulcer index = 2900), was associated with a significant increase of tumor necrosis factor-alpha and malondialdehyde, and significant decrease of the gastroprotective mediators prostaglandin E2, glutathione (GSH) and nitric oxide (NO) compared with normal control. Pretreatment with AGE produced comparable results with those obtained in the omeprazole group; the preventive index in the AGE group was 83.4% compared with 94.5% in the omeprazole group. The prophylactic role of AGE in indomethacin-induced ulcer was, in part, mediated by decreasing oxidative stress and increasing gastric level of PGE2, GSH, and NO. CONCLUSION: AGE corrected the histopathological abnormalities in gastric tissue and proved a promising gastroprotective role in gastric ulcer.