Atranorin from lichens act as potential inhibitor for cervical tumor proteins TGFbeta and kinase enzyme CDK4/CyclinD3: An anti-cancer intervention therapy

In the present study a potential anticancer compound atranorin was identified and isolated from the foliose lichen Heterodermia boryi. The study also evaluated the pharmacological potential of the foliose lichens Sticta weigelii and Heterodermia boryi against cervical cancer. Qualitative analysis of phytochemicals revealed the presence of alkaloids, flavonoids, phenolics, terpenoids and tannin compounds in both lichens. Saponins and glycosides are present only in S. weigelii. The presence of atranorin in H. boryi was confirmed by HPTLC, and its structure was elucidated by ¹H and ¹³C NMR, whereas atranorin was not present in S. weigelii. The in vitro antioxidant activity of atranorin was 2 to 2.5-fold greater than that of the acetone crude extract of H. boryi and S. weigelii respectively. The result of the in vitro MTT assay of lichen extracts reveals that IC50 value of 150.20 μg/ml and 130.55 μg/ml respectively for S. weigelii and H. boryi, whereas atranorin and avastin exhibit a significant IC50 value of 70.60 and 49.75 μg/ml respectively. The carcino embryonic antigen (CEA) level was restored to a normal level in atranorin treated animal group than lichen samples treated animal groups. In in vivo studies, animals treated with 500 mg/ml extract of three lichens and 100 mg of atranorin presented no evidence of malignancy/dysplasia/loss of polarity in sections of cervical cancer cells. The results revealed that cervical tumor burden and tumor weight in control animals were 0.6725 g, whereas in lichen treated animal groups were in the range of 0.3971–0.5703 g of tumor tissue. Atranorin significantly reduces tumor growth and weight in atranorin-treated animals up to 0.3236 g. Finally, in silico analysis revealed that atranorin exhibits stronger binding affinity to all three cervical cancer target proteins (DHFR, TGF-1beta, estrogen receptor) than reference standard drug topotecan. Based on our findings that atranorin isolated from H. boryi has excellent anticancer potential against cervical cancer, as validated in vitro, in vivo, and in silico approaches, atranorin can serve as a potential drug candidate to treat cervical cancer, but further clinical validation is needed before its commercialization.