ABSTRACT
AIM: The study aimed to assess the anticancer effects of leaves of the male and female plant and seeds Carica papaya L. extract and the active compound benzyl isothiocyanate on oral squamous cell carcinoma (OSCC) cell line. MATERIALS AND METHODS: Extracts of CO2 strain C. papaya L. seeds were prepared using water, ethanol, and ethanol:water by maceration, and benzyl isothiocyanate was quantified. Alkaloid fractions of leaves of male and female plants of C. papaya L. were prepared and quantified. The anticancer effects of the test substances on the SCC-25 cell line were assessed by MTT, apoptosis assay, cell cycle analysis, and determination of mitochondrial membrane potential. RESULTS: The ethanol:water extract of C. papaya L. (seeds) demonstrated the highest quantity of benzyl isothiocyanate. Male plant leaves demonstrated greater alkaloid content. The leaves of the male plant exhibited apoptosis induction and S-phase arrest, whereas the leaves of the female plant and seeds of C. papaya L. demonstrated G2M-phase arrest and apoptosis induction. CONCLUSION: C. papaya L. and benzyl isothiocyanate demonstrated anticancer effects. There was a difference in the anticancer effects of leaves of male and female plants of C. papaya L. CLINICAL SIGNIFICANCE: The anticancer effects of papaya leaves and seeds could be further explored to develop an adjunct therapy for oral cancer to improve prognosis and reduce recurrence rates.
Subject(s)
Antineoplastic Agents , Carcinoma, Squamous Cell , Carica , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Plant Extracts/pharmacology , Carcinoma, Squamous Cell/drug therapy , Squamous Cell Carcinoma of Head and Neck , Mouth Neoplasms/drug therapy , Antineoplastic Agents/pharmacology , Cell Line , Plant LeavesABSTRACT
The mitochondrial damage in the lung was assessed by examining the levels of reactive oxygen species (ROS), lipid peroxides, reduced glutathione, and the activities of isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, complexes I to IV, and cytochrome c. The oxidative phosphorylation (levels of adenosine triphosphatase) was evaluated for the assessment of mitochondrial functional capacity. We found significantly elevated levels of ROS, lipid peroxides, and decreased levels of mitochondrial enzymes in the mice administered with benzo[a]pyrene (B[a]p). Measurement of oxidative phosphorylation revealed a marked depletion in all the variables studied. Administration of crocetin prevented the structural and functional impairment of mitochondria upon administration to B[a]p. From the results, we suggest that administration of B[a]p induces damage to the lung mitochondria and crocetin protects the lung from damage by maintaining the structural and functional integrity of the mitochondrial membrane.
Subject(s)
Antioxidants/pharmacology , Benzo(a)pyrene/antagonists & inhibitors , Benzo(a)pyrene/toxicity , Carcinogens/antagonists & inhibitors , Carcinogens/toxicity , Carotenoids/pharmacology , Mitochondria/drug effects , Oxidative Stress/drug effects , 8-Hydroxy-2'-Deoxyguanosine , Adenosine Triphosphatases/metabolism , Animals , Blotting, Western , Chromatography, High Pressure Liquid , DNA Damage , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/metabolism , Erythrocyte Membrane/drug effects , Erythrocyte Membrane/enzymology , Erythrocyte Membrane/metabolism , In Vitro Techniques , Lung/drug effects , Lung/metabolism , Male , Malondialdehyde/metabolism , Membrane Fluidity/drug effects , Membrane Potentials/drug effects , Mice , Mitochondria/enzymology , Reactive Oxygen Species/metabolism , Vitamin A/analogs & derivativesABSTRACT
Naringenin is a flavanone that is believed to have many biological actions, including as an anti-oxidant, free radical scavenger and an antiproliferative agent. The global incidence of gastric carcinoma is increasing rapidly, more than for any other cancer. Therefore, in the present study, we tested the effects of naringenin on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and saturated sodium chloride (S-NaCl) in rats. Male Wistar rats were divided into five groups and treated over a period of 20 weeks as follows: (i) a control group given corn oil (1 mL/rat, p.o.) daily 20 weeks; (ii) 200 mg/kg, p.o., MNNG on Days 0 and 14 with S-NaCl (1 mL/rat) administered twice a week for the first 3 weeks; (iii) 200 mg/kg, p.o., MNNG on Days 0 and 14, with naringenin (200 mg/kg, p.o., daily) treatment for the entire 20 weeks; (iv) 200 mg/kg, p.o., MNNG on Days 0 and 14, with naringenin treatment (200 mg/kg, p.o., daily) initiated from 6 to 20 weeks; (v) 200 mg/kg, p.o., naringenin alone daily for 20 weeks. In Group II rats in which gastric cancer was inducted with MNNG and S-NaCl, there was a significant increase in hydrogen peroxide and lipid peroxidation levels, with decreases in reduced glutathione, oxidized glutathione, glutathione peroxidase, glutathione reductase and glucose 6-phosphate dehydrogenase. In addition, in Group II rats with gastric cancer, there were significant increases in the activity of cytochrome P450, cytochrome b(5) and NADPH cytochrome c reductase, with concomitant decreases in the activity of the phase II enzymes glutathione S-transferase and UDP-glucuronosyl transferase. Naringenin treatment (Groups III and IV) restored enzyme activity to near control levels. These results indicate that naringenin has a chemopreventive action against MNNG-induced gastric carcinoma in experimental rats.
