Cirsimaritin, a lung squamous carcinoma cells (NCIH-520) proliferation inhibitor

Abstract

Cirsimaritin is a dimethoxy flavone, which is present in Ocimum sanctum, Microtea debilis, Artemisia judaica, Cirsium japonicum, and Lithocarpus dealbatus. Its antiproliferative potential has been explored in breast and gall bladder cancer cell lines. However, no reports are available on skin and squamous lung carcinoma. Also, the complete mode of action is unknown. Therefore, in the present study, the anticancer potential of cirsimaritin is explored in organ-specific cell lines by using MTT assay. Further, the inhibitory potential and binding interaction with the selected targets were analyzed through in vitro and in-silico analysis. Cirsimaritin showed selective anticancer activity against NCIH-520 cell-line (IC₅₀ 23.29 µM), also inhibited the proliferation of other cell-lines up to 48% at 100 µM. In NCIH-520 cell-line, cirsimaritin significantly increased the apoptosis of the cells at both the tested concentrations (10 and 100 µM), which was confirmed by Annexin-V signifying the induction of late apoptosis. Besides, an increase in the ROS levels of 1.6 fold (10 µM) and 1.8 fold (100 µM), circimaritin also inhibits the activity of ODC and CATD with the IC₅₀ 57.30 and 68.22 µM respectively. It exhibited a good binding score with the selected targets, follow Lipinski’s rule of five and non-mutagenic. Hence, cirsimaritin is a potent molecule, which inhibits the proliferation of lung squamous cell lines by inducing apoptosis. It also inhibited the activity of ODC and CATD responsible for the progression phase in the cancer cells.

Communicated by Ramaswamy H. Sarma

Keywords:

• Cirsimaritin
• anticancer
• ROS
• apoptosis
• ornithine decarboxylase
• cathepsin D

Acknowledgements

We are thankful to the Director, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow for rendering the necessary facilities required to perform various experimental work. S.S, P.K, and W.R are thankful to CSIR and UGC for their fellowships.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported in part from SERB-DST, New Delhi, India Grant No: EEQ/2016/000121, CSIR-Phytopharma Mission Project (HCP-010), and CST-UP, Lucknow, India Grant No. GAP-394.