Rosmarinic Acid-Rich Fraction from Mentha arvensis Synchronizes Bcl/Bax Expression and Induces Go/G1 Arrest in Hepatocar
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RESEARCH ARTICLE
Rosmarinic Acid-Rich Fraction from Mentha arvensis Synchronizes Bcl/Bax Expression and Induces Go/G1 Arrest in Hepatocarcinoma Cells Chinnu Jerard1 • Bibin Punnoose Michael1 • Smitha Chenicheri2 • Nithin Vijayakumar1 • Rajesh Ramachandran1
Received: 27 November 2018 / Revised: 4 July 2019 / Accepted: 6 July 2019 The National Academy of Sciences, India 2019
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 lg 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. Graphic Abstract
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. & Rajesh Ramachandran [email protected] 1
Biogenix Research Center for Molecular Biology and Applied Sciences, KRRA-31, Keshavadev Road, Poojappura, Thiruvananthapuram, Kerala 695012, India
2
PMS College of Dental Science and Research, Thiruvananthpuram, Kerala, India
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Keywords Rosmarinic acid Hepatocellular carcinoma Cell cycle Bcl-2 ERK2
Introduction Hepatocellular carcinoma (HCC), the most universal liver cancer, is customarily investigated at a progressive stage due to poor lookout [1]. HCC stands second among deaths due to cancer, where it is the fifth highest in males and ninth highest in females when compared with other malignancies [2]. Although chemotherapeutic agents have been tried by clinicians to extend the survival rate of HCC patients, the patient longevity is restricted because of their elevated cost and detrimental side effects [3]. Since the use of herbal natural products has become increasingly popular worldwide and myriad spectrum of herb species has been recognized to have medicinal properties and beneficial impact on health [4
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