Apoptotic and antimetastatic activities of betulin isolated from against non-small cell lung cancer cells.

BACKGROUND

Globally, the prevalence and mortality rates of lung cancer have been escalated with the increasing trend of tobacco smoking. The toxicity and irresponsive nature of the available drugs for lung cancer treatment demands an alternative approach.

METHODS

In this study, four known compounds namely, cirsimaritin (4',5, -dihydroxy-6,7-di-methoxyflavone) (1), eupatorin (5,3'-dihydroxy-6,7,4'-trimethoxyflavone) (2), betulin (Lup-20 (29)-ene-3, 28-diol) (3), and β-amyrin acetate (12-Oleanen-3yl acetate) (4) have been isolated from the leaves extract of . Preliminary screening of these natural compounds (1-4) was performed against non-small cell lung carcinoma (NCI-H460) and normal mouse fibroblast (NIH-3T3) cell lines.

RESULTS

The compounds were found to be antiproliferative against cancer cells with wide therapeutic index in comparison to the normal cells. Effects of betulin (3) on cell migration, invasion, apoptosis, and expression of important apoptosis- and metastasis-related markers were observed at different concentrations. The results showed significant dose-dependent induction of apoptosis after the treatment with betulin (3) followed by increased expression of the caspases family (ie, caspase-3, -6, and -9), proapoptotic genes ( and ), and inhibiting anti-apoptotic genes ( and ). Furthermore, wound healing and transwell invasion assays suggested that betulin (3) could also regulate metastasis by inhibiting MMP-2/-9. Osteopontin, a central regulator of apoptosis and metastasis was also inhibited in a dose-dependent manner.

CONCLUSION

The present findings suggest that betulin (3) can be an attractive chemotherapeutic target for treating resistant lung cancers.