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Rosmarinic Acid-Rich Fraction from Mentha arvensis Synchronizes Bcl/Bax Expression and Induces Go/G1 Arrest in Hepatocarcinoma Cells

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Proceedings of the National Academy of Sciences, India Section B: Biological Sciences Aims and scope Submit manuscript

Abstract

Hepatocellular carcinoma (HCC) stands second among deaths due to cancer. Although chemotherapeutic agents are being tried by clinicians to extend the survival rate of HCC patients, patient longevity is restricted because of the detrimental side effects of chemotherapeutic drugs. Rosmarinic acid (Ra), a natural phenolic compound, possesses numerous biological properties including antioxidant, anti-inflammatory, anti-angiogenic, anti-fibrosis, hepatoprotective and anticancer activities. Rosmarinic acid fraction isolated from Mentha arvensis extract (RaMa) was subjected to study the molecular mechanism of anticancer activity in vitro. HPLC analysis of RaMa has conferred an appreciable amount of Ra present in the extract. Apart from the antioxidant and antibacterial activity, RaMa induced dose-dependent cell death in cultured HepG2 (human hepatocellular carcinoma) cells with an LD50 of 27.622 µg mL−1 and was found to induce apoptosis. Fluorescence-activated cell sorting (FACS) analysis has shown distinct cell cycle arrest at Go/G1 phase in cells treated with RaMa and mRNA expression studies affirmed downregulation of the anti-apoptotic gene, Bcl-2 along with upregulation of pro-apoptotic genes Bax and ERK2 by Ra administration.

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Acknowledgements

The authors are thankful to all the staff in Biogenix Research Center for Molecular Biology and Applied Sciences for their assistance to undertake the work.

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  1. Biogenix Research Center for Molecular Biology and Applied Sciences, KRRA-31, Keshavadev Road, Poojappura, Thiruvananthapuram, Kerala, 695012, India

    Chinnu Jerard, Bibin Punnoose Michael, Nithin Vijayakumar & Rajesh Ramachandran

  2. PMS College of Dental Science and Research, Thiruvananthpuram, Kerala, India

    Smitha Chenicheri

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  1. Chinnu Jerard
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Significance Statement Rosmarinic acid specifically isolated and purified from M. arvensis was evaluated for its inhibition on growth and proliferation of liver cancer which is not reported previously. Go/G1 phase arrest induced by RA can be attributed as synchronization of Bcl2-induced apoptosis.

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Jerard, C., Michael, B.P., Chenicheri, S. et al. Rosmarinic Acid-Rich Fraction from Mentha arvensis Synchronizes Bcl/Bax Expression and Induces Go/G1 Arrest in Hepatocarcinoma Cells. Proc. Natl. Acad. Sci., India, Sect. B Biol. Sci. 90, 515–522 (2020). https://doi.org/10.1007/s40011-019-01122-9

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