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.