الفهرس | Only 14 pages are availabe for public view |
Abstract The activity of Aldehyde dehydrogenase (ALDH) has been involved in multiple biological and biochemical pathways. It is used as a potential marker for cancer stem cells (CSCs). The present study aimed at investigation of the functional role of ALDH-1 during cellular proliferation and tumor formation in chemically-induced lung cancer in mice. The antitumor impact of desert dates (D.D) ethanolic extract on mouse lung carcinogenesis either individually or in combination with Gemcitabine as standard chemotherapy also has been studied. Five-six weeks male balb c mice were divided into six groups: first vehicle group received saline and corn oil only was -ve controls. The second was administered with urethane(0.001mg/kg) one time intraperitoneally (i.p.) then injected with BHT (125 mg /kg, then 150 mg /kg each one time a week then with 200 mg/kg once a week) for 7 weeks. This group used as +ve control group. The third and fourth groups were injected with equal doses of urethane/BHT and posttreated orally with 200 or 400 (mg/kg) D.D. extract, respectively, twice a week for a period of four weeks. The fifth group was injected with urethane/BHT then treated with gemcitabine (160 mg/kg) (i.p.) once a week for six weeks. Finally, the sixth group was injected with urethane/BHT and then treated by D.D. extract with a dose of 200 mg/kg orally two times per week for a period of 4 weeks plus gemcitabine (80 mg/kg) once a week for six weeks. Our results revealed that D.D extract exerted anti-tumor effects against lung cancer by reducing tumor multiplicities and averages of tumor areas alone or in combination with Gemcitabine. The biochemical changes in the hepatic and lung tissues of urethane/BHT positive control mice were improved by D.D. alone or in combination with Gemcitabine. Also, the combination of D.D. and Gemcitabine showed potent apoptosis-inducing.The same results are shown in immune-histochemistry for PCNA, reduction of the level of Aldehyde Dehydrogenase (ALDH-1) activity and CD133 numbers. The D.D. extract induced cell cycle arrest in combination with gemcitabine at G0/G1 phase. In conclusion the data demonstrate that Balanites aegyptiaca extract optimizes the antitumor capability of Gemcitabine and could be utilized as natural neoadjuvant medication and the role of ALDH-1 in identifying lung cancer stem cells. |