Qualification: 
Ph.D, M. Pharm.
lekshmirnath@aims.amrita.edu

Dr. Lekshmi R. Nath joined as Assistant Professor in the Department of Pharmacognosy at Amrita School of Pharmacy in January 2018. She received her PhD from Rajiv Gandhi Centre for Biotechnology (RGCB), Trivandrum, Kerala. The title of her PhD thesis was “In vitro and in vivo evaluation of the anticancer effect of active principles from Solanum nigrum Linn and Chromolaena odorata". During her PhD, she has evaluated the anticancer potential and pharmacological safety of Uttroside B and kaempferide using both in vitro and in vivo models. She completed her M.Pharm. from KLE University's College of Pharmacy, Karnataka (Formerly known as KLES college of Pharmacy) and B.Pharm from Dept of Pharmaceutical Sciences, MG University, Kottayam. She has also served as a faculty at the Dale View College of Pharmacy, Trivandrum during 2008-2009. She has 9 years research experience in the area of anticancer compounds at RGCB. She received ICMR and CICS travel grant to present a scientific paper in Euro Biotechnology Congress -2015 held at Frankfurt Main, Germany in August 2015.

Faculty Research Interest

  • Bioprospecting of anticancer compounds
  • Chemotherapy
  • Chemoprevention
  • Cell death mechanism

Achievements and  Awards

  • Senior Research Fellowship (SRF) from Indian Council of Medical Research (ICMR) in February 2011
  • OMICS International Best Poster Award at the 8th Eurobiotechnology congress, Frankfurt Main, Germany, August 2015
  • Best paper Award under Biotechnology category for oral presentation at 28th Kerala Science Congres, University of Calicut Campus, Thenhipalam, Malappuram District, India, January 2016
  • Best Oral Presentation award in the “International Conference on Neutraceuticals in Chronic Disease-2016 held at Kochi, Kerala, India, September 2016
  • Dr M.R. Das Career Award in recognition of the Professional achievement during PhD tenure in RGCB, December 2016
  • Kerala State Council For Science, Technology And Environment (KSCTEC) Best Paper Award for Project “Mechanistic evaluation of the anti-tumour effect of SN2, the active principle of Solanum nigrum Linn in hepatocellular carcinoma, 2016 July-December 2017.

Publications

Publication Type: Patent

Year of Publication Publication Type Title

2016

Patent

Lekshmi R Nath and Anto, R. John, “Uttroside B and Derivatives Thereof as Therapeutics for Hepatocellular Carcinoma”, U.S. Patent 2016410184012016.

Publication Type: Journal Article

Year of Publication Publication Type Title

2016

Journal Article

Lekshmi R Nath, Gorantla, J. N., Thulasidasan, A. T., Vijayakurup, V., Shah, S., Anwer, S., Joseph, S. M., Antony, J., Veena, K. Suresh, Sundaram, S., Marelli, U. K., Lankalapalli, R. S., and Anto, R. John, “Evaluation of Uttroside B, a Saponin from Solanum Nigrum Linn, as a Promising Chemotherapeutic Agent Against Hepatocellular Carcinoma”, Sci. Rep. 2016, vol. 6, 2016.[Abstract]


We report, for the first time, the remarkable efficacy of uttroside B, a potent saponin from Solanum nigrum Linn, against liver cancer. The compound has been isolated and characterized from the leaves of Solanum nigrum Linn, a plant widely used in traditional medicine and is a rich resource of several anticancer molecules. Uttroside B, that comprises of β-D-glucopyranosyl unit at C-26 of the furostanol and β-lycotetraosyl unit at C-3, is ten times more cytotoxic to the liver cancer cell line, HepG2 (IC50: 0.5 μM) than sorafenib (IC50: 5.8 μM), the only FDA-approved drug for liver cancer. Moreover, it induces cytotoxicity in all liver cancer cell lines, irrespective of their HBV status, while being non-toxic to normal immortalized hepatocytes. It induces apoptosis in HepG2 cells by down-regulating mainly the activation of MAPK and mTOR pathways. The drastic reduction in HepG2-xenograft tumor size achieved by uttroside B in NOD-SCID mice and substantiation of its biological safety through both acute and chronic toxicity studies in Swiss albino mice warrants clinical validation of the molecule against hepatic cancer, for which, the chemotherapeutic armamentarium currently has limited weapons.

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2016

Journal Article

Lekshmi R Nath, Kumar, S. N., Das, A. A., Nambisan, B., Shabna, C. Mohandas, and Anto, R. J., “In Vitro Evaluation of the Antioxidant, 3,5-Dihydroxy-4-Ethyl-Trans-Stilbene (DETS) Isolated from Bacillus Cereus as a Potent Candidate Against Malignant Melanoma”, Frontiers in Microbiology, vol. 7, no. 452, 2016.[Abstract]


3,5-dihydroxy Q1 -4-ethyl-trans-stilbene (DETS) is a natural stilbene, which was first identified as bioactive bacterial secondary metabolite isolated from Bacillus cereus associated with a rhabditid entomopathogenic nematode. The present study was intended to investigate the antioxidant and anticancer activity of this compound in vitro. Antioxidant activity was investigated by assaying DPPH free radical scavenging, superoxide radical-(O2..) scavenging, hydroxyl radical scavenging and metal chelating activity, which proved that the compound is a powerful antioxidant. The metal chelating activity of DETS was higher than butylated hydroxyanisol (BHA) and gallic acid, two well-known antioxidants. As the molecule exhibited strong antioxidant potential, it was further evaluated for cytotoxic activity toward five cancer cells of various origins. Since the compound has a strong structural similarity with resveratrol (trans- 3,4,5-trihydroxystilbene), a well-studied chemopreventive polyphenolic antioxidant, its anticancer activity was compared with that of resveratrol. Among the five cancer cells studied, the compound showed maximum cytotoxicity toward the human melanoma cell line, [A375, IC50: 24.01 μM] followed by cervical [HeLa-46.17 μM], colon [SW480- 47.28 μM], liver [HepG2- 69.56 μM] and breast [MCF-7- 84.31 μM] cancer cells. A375 was much more sensitive to DETS compared to the non-melanoma cell line, A431, in which the IC50 of the compound was more than double (49.60 μM). In the present study, the anticancer activity of DETS against melanoma was confirmed by various apoptosis assays. We also observed that DETS, like resveratrol, down-regulates the expression status of major molecules contributing to melanoma progression, such as BRAF, β-catenin and Brn-2, all of which converge in MITF-M, the master regulator of melanoma signaling. The regulatory role of MITF-M in DETS-induced cytotoxicity in melanoma cells was confirmed by comparing the cytotoxicity of DETS in A375 cells (IC50-24.01 μM), with that in SK-MEL-2 (IC50-67.6 μM), another melanoma cells which highly over-express MITF-M. The compound arrests the cells at S-G2 transition state of the cell cycle, as resveratrol. Our results indicate that DETS is a powerful antioxidant, having anticancer efficacy comparable with that of resveratrol, and is a potential candidate to be explored by in vivo studies and in-depth mechanistic evaluation. To our knowledge, this is the first report on the antioxidant and anticancer properties of DETS.

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2015

Journal Article

Lekshmi R Nath, Gorantla, J. N., Joseph, S. Margaret, Antony, J., Thankachan, S., Menon, D. B., S. Sankar, Lankalapalli, R. S., and Anto, R. John, “Kaempferide, the Most Active Among the Four Flavonoids Isolated and Characterized from Chromolaena Odorata, Induces Apoptosis in Cervical Cancer Cells While Being Pharmacologically Safe”, RSC Advances, vol. 5, pp. 100912-100922, 2015.[Abstract]


Chromolaena odorata, commonly known as Siam weed, is popular as a traditional medicine. We report the isolation and characterization of four compounds from a cytotoxic fraction, F-17, isolated from the dichloromethane (DCM) extract of C. odorata by bioactivity-guided fractionation. The organic extracts were screened in five cancer cell lines of various origins for their cytotoxic effect. The DCM extract exhibited maximum cytotoxicity and was purified by silica gel column chromatography to obtain four major compounds. The compounds were characterized by 1H-NMR, 13C-NMR, and HR-MS methods and were found to be acacetin (1), dihydrokaempferide (2), isosakuranetin (3), and kaempferide (4). MTT assay was used for preliminary evaluation of the cytotoxicity of these compounds. Among the cancer cell lines that were screened, HeLa was the most sensitive to kaempferide (IC50: 16 μM) followed by acacetin (174 μM), dihydrokaempferide (>200 μM) and isosakuranetin (>200 μM). Kaempferide (4) induced morphological characteristics of apoptosis in HeLa cells and was non-toxic to rapidly dividing normal human fibroblasts up to 100μM. Annexin V staining, characteristic of early stage of apoptosis was further confirmed by FACS analysis. Induction of apoptosis was illustrated by its potential to induce the cleavage of caspases and PARP. FACS analysis demonstrated that kaempferide (4)-induced cytotoxicity is independent of cell cycle arrest. Acute and chronic toxicity studies conducted in vivo proved that the compound is pharmacologically safe. To the best of our knowledge, this is the first study reporting the anticancer potential and pharmacological safety of kaempferide (4).

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2015

Journal Article

J. Antony, Saikia, M., .V, V., Lekshmi R Nath, Katiki, M. Rao, Murty, M. S. R., Paul, A., A, S., Chandran, H., Joseph, S. Margaret, S, N. Kumar., Panakkal, E. Jayex, I.V, S., I.V, S., Ran, S., S, S., Rajan, E., and Anto, R. John, “DW-F5: A Novel Formulation Against Malignant Melanoma from Wrightia Tinctoria”, Scientific Reports, 2015.[Abstract]


Wrightia tinctoria is a constituent of several ayurvedic preparations against skin disorders including psoriasis and herpes, though not yet has been explored for anticancer potential. Herein, for the first time, we report the significant anticancer properties of a semi-purified fraction, DW-F5, from the dichloromethane extract of W. tinctoria leaves against malignant melanoma. DW-F5 exhibited anti-melanoma activities, preventing metastasis and angiogenesis in NOD-SCID mice, while being non-toxic in vivo. The major pathways in melanoma signaling mediated through BRAF, WNT/β-catenin and Akt-NF-κB converging in MITF-M, the master regulator of melanomagenesis, were inhibited by DW-F5, leading to complete abolition of MITF-M. Purification of DW-F5 led to the isolation of two cytotoxic components, one being tryptanthrin and the other being an unidentified aliphatic fraction. The overall study predicts Wrightia tinctoria as a candidate plant to be further explored for anticancer properties and DW-F5 as a forthcoming drug formulation to be evaluated as a chemotherapeutic agent against malignant melanoma.

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2014

Journal Article

R. E. K, Bava, S. V., Narayanan, S. Shyam, Lekshmi R Nath, Thulasidasan, A. Kumar, V, S. E., and Anto, R. John, “[6]-Gingerol Induces Caspase-Dependent Apoptosis and Prevents PMA-Induced Proliferation in Colon Cancer Cells by Inhibiting MAPK/AP-1 Signaling”, PLOS ONE, vol. 9, no. 8, 2014.[Abstract]


We report mechanism-based evidence for the anticancer and chemopreventive efficacy of [6]-gingerol, the major active principle of the medicinal plant, Ginger (Zingiber officinale), in colon cancer cells. The compound was evaluated in two human colon cancer cell lines for its cytotoxic effect and the most sensitive cell line, SW-480, was selected for the mechanistic evaluation of its anticancer and chemopreventive efficacy. The non-toxic nature of [6]-gingerol was confirmed by viability assays on rapidly dividing normal mouse colon cells. [6]-gingerol inhibited cell proliferation and induced apoptosis as evidenced by externalization of phosphatidyl serine in SW-480, while the normal colon cells were unaffected. Sensitivity to [6]-gingerol in SW-480 cells was associated with activation of caspases 8, 9, 3 &7 and cleavage of PARP, which attests induction of apoptotic cell death. Mechanistically, [6]-gingerol down-regulated Phorbol Myristate Acetate (PMA) induced phosphorylation of ERK1/2 and JNK MAP kinases and activation of AP-1 transcription factor, but had only little effects on phosphorylation of p38 MAP kinase and activation of NF-kappa B. Additionally, it complemented the inhibitors of either ERK1/2 or JNK MAP kinase in bringing down the PMA-induced cell proliferation in SW-480 cells. We report the inhibition of ERK1/2/JNK/AP-1 pathway as a possible mechanism behind the anticancer as well as chemopreventive efficacy of [6]-gingerol against colon cancer

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2010

Journal Article

Lekshmi R Nath, KP, M., RV, S., and KS, A., “Anti-inflammatory activity of Mirabilis jalapa linn. Leaves”, J Basic Clin Pharm, vol. 1, no. 2, 2010.[Abstract]


Mirabilis Jalapa Linn. is a widely used traditional medicine in many parts of the world for the treatment of various diseases viz. virus inhibitory activity, anti tumour activity. It is claimed in traditional medicine that the leaves of the plant are used in the treatment of inflammation. In the present study, the total alcoholic extract and successive petroleum ether fractions of leaves of Mirabilis Jalapa Linn were screened for its anti-inflammatory activity using carageenan induced rat paw edema and cotton pellet induced granuloma models. The total alcoholic extract at the dose of 300 mg/kg p.o and successive petroleum ether fraction at the dose of 200 mg/kg exhibited significant anti-inflammatory activity in carrageenan induced paw edema model (p<0.01). In cotton pellet granuloma model, the total alcoholic extract at the dose of 300 mg/kg and successive petroleum ether fraction at the dose of 200 mg/kg inhibited granuloma formation significantly (p<0.05) indicating that both test samples inhibit the increase in number of fibroblasts and synthesis of collagen and mucopolysaccharides during granuloma tissue formation during the chronic inflammation. These experimental results have established a pharmacological evidence for the folklore claim of the drug to be used as an anti inflammatory agent.

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2009

Journal Article

Lekshmi R Nath, KP, M., RV, S., and K.S, A., “Pharmacognostical and Phytochemical Studies of Mirabilis jalapa Linn. leaves”, Pharmacognosy Journal, vol. 1, no. 2, pp. 111 - 115, 2009.[Abstract]


The Mirabilis jalapa stem were collected, dried and studied to determine the various parameters of pharmacognostical standards such as ash and extractive values,
microscopical characters of stem powder phytochemical tests. The shade dried powder and different types of extracts (viz., aqueous, benzene, chloroform, dichloromethane, methanol) have been analyzed for their preliminary phytochemical tests.

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