Chemopreventive and chemotherapeutic activities of Dracaena cinnabari balf.f against oral cancer in vivo / Nashwan Abdullah Abdo al-Afifi

Nashwan Abdullah, Abdo al-Afifi (2018) Chemopreventive and chemotherapeutic activities of Dracaena cinnabari balf.f against oral cancer in vivo / Nashwan Abdullah Abdo al-Afifi. PhD thesis, University of Malaya.

	PDF (The Candidate's Agreement) Restricted to Repository staff only Download (1667Kb)
Preview	PDF (Thesis PhD) Download (6Mb) | Preview

Abstract

Dracaena cinnabari (DC) is a perennial tree possesses various pharmacological properties but its anticancer properties have not been clarified. Aims: To evaluate the toxicity, anticancer activity (chemopreventive and chemotherapeutic) and metastasis obstruction of the DC resin methanol extract on 4-nitroquinoline-1-oxide (4NQO)-induced oral cancer in rats. Materials and Methods: The powder of DC resin was extracted with methanol using the maceration extraction method. The toxicity profile of DC extract was investigated in Sprague Dawley (SD) rats using acute and sub-acute oral toxicity tests. In general, the chemopreventive study involves administration of 4NQO solution (cancer induction) to SD rats for 8 weeks alone or with DC extract at 100, 500 and 1000 mg/kg that started one week before the exposure until one week after the cessation of the carcinogen exposure. In the chemotherapeutic study, SD rats were given 4NQO (20 ppm) for 8 weeks followed by administration of DC extract at 100, 500 and 1000 mg/kg for another 10 weeks with or without Cisplatin (3 mg/kg I.P for every 3 weeks). All rats from both studies were sacrificed after 22 weeks, and histological analysis was performed to assess any incidence of pathological changes. Immunohistochemical expressions of selected tumour marker antibodies were analysed using an image analyser computer system, and the expression of selected genes involved in apoptosis and proliferative mechanism related to oral cancer were evaluated using RT2-PCR. Result: Acute oral toxicity revealed that the DC extract could be well tolerated up to the dose of 2000 mg/kg and at the dose of 1500 mg/kg, the sub-acute test revealed no evidence of any treatment-related changes of the animals used in this study. In the chemopreventive study, the incidence of OSCC decreased with the administration of DC extract at 100, 500 and 1000 mg/kg compared to the induced cancer and vehicle groups. In the chemotherapeutic study, there was no incidence of OSCC (0%) with the administration of DC 1000 mg/kg and Cisplatin. For both chemopreventive and chemotherapeutic studies, the survival rate increased to 100% for DC doses of 500 and 1000 mg/kg. The developed tumour was also observed to be smaller, and lymph node metastasis was inhibited in all DC treated groups with or without Cisplatin when compared to the induced cancer and vehicle groups. The DC 1000 mg/kg group inhibit the expression of Cyclin D1, Ki-67, Bcl-2 and p53 genes responsible for decreasing the transformation and the aggressiveness of the cancer tissue while a slight increase in the expression of β-catenin and E-cadherin genes that decrease the proliferation of cancer cells while maintaining epithelial polarity was observed. It was also observed that DC 1000 mg/kg induced apoptosis by upregulation of Bax and Casp3 genes and down-regulation of Tp53, Bcl-2, Cox-2, Cyclin D1 and EGFR genes when compared to the induced cancer group. Conclusion: This study provides scientific validation for the safety of DC extract up to the highest dose level used in this study. Furthermore, the data indicated that systemic administration of the DC extract has anticarcinogenic potency on oral carcinogenesis.

Actions (For repository staff only : Login required)