Pro-apoptotic, anti-metastatic, and anti-telomerase activity of Tinospora cordifolia and its active polysaccharide arabinogalactan during Benzo(a)pyrene-induced lung carcinogenesis.

Abstract

BACKGROUND:The present study aims to unravel the pro-apoptotic, anti-metastatic, and anti-telomerase activity of aqueous extract of Tinospora cordifolia stem (Aq.Tc) and its active component arabinogalactan (AG) during Benzo(a)pyrene [B(a)P]-induced lung tumorigenesis in mice.MATERIALS AND METHODS:Lung tumors were induced in male BALB/c mice using B(a)P as a carcinogen. Animals were administered twice with 50 mg/kg b.wt (i.p.) dosage of B(a)P at the 2nd and 4th week of the study. Mice were orally treated with Aq.Tc and AG on alternate days at a dose of 200 mg/kg b.wt and 7.5 mg/kg b.wt, respectively, for continuous 22 weeks.RESULTS:Oral administration of animals with Aq.Tc and AG suppressed the development of lung carcinogenesis by modulating the mRNA and protein expressions of different apoptotic genes; bcl-2, bax, caspase 3, and caspase 9. The pro-apoptotic proficiency of Aq.Tc and AG was further confirmed by DNA agarose gel electrophoresis showing fragmentation in B(a)P + Aq.Tc group and smear formation in B(a)P + AG group. In contrast to the control group, an increase in tumor invasion factors such as matrix metalloproteinases-2 (MMP-2) and MMP-9 was also observed in B(a)P treated animals. Nevertheless, Aq.Tc and AG treatment effectively mitigated the B(a)P-induced upregulation of MMP-2 and MMP-9. The activity of the telomerase enzyme was also observed to be upregulated in B(a)P treated animals which consecutively found to get normalized with the parallel administration of Aq.Tc and AG.CONCLUSION:Aq.Tc and AG successfully mitigated the altered expression of apoptosis, metastasis, and telomerase activity-associated genes during pulmonary carcinogenesis.