Evaluation of anticancer potential of Bacopa monnieri L. against MCF-7 and MDA-MB 231 cell line

Mallick, Md. Nasar; Akhtar, Md. Salman; Najm, Mohd. Zeeshan; Tamboli, ET; Ahmad, Sayeed; Husain, Syed Akhtar

doi:10.4103/0975-7406.168038

Cited by 25 publications

(15 citation statements)

References 13 publications

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“…Plant extracts of Bacopa monnieri have been shown to be cytotoxic both in vitro and in vivo in several cancer cell lines including those of colon, lung and breast [ 10 , 11 ]. However, there are only limited studies that have specifically investigated the anti-tumour effects of purified bacopaside II.…”

Section: Introductionmentioning

confidence: 99%

The Purified Extract from the Medicinal Plant Bacopa monnieri, Bacopaside II, Inhibits Growth of Colon Cancer Cells In Vitro by Inducing Cell Cycle Arrest and Apoptosis

Smith

Palethorpe

Tomita

et al. 2018

Cells

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Aquaporin-1 (AQP1), a transmembrane pore-forming molecule, facilitates the rapid movement of water and small solutes across cell membranes. We have previously shown that bacopaside II, an extract from the medicinal herb Bacopa monnieri, blocks the AQP1 water channel and impairs migration of cells that express AQP1. The aim of this study was to further elucidate the anti-tumour potential of bacopaside II in colon cancer cells. Expression of AQP1 in HT-29, SW480, SW620 and HCT116 was determined by quantitative PCR and western immunoblot. Cells were treated with bacopaside II, and morphology, growth, autophagy, cell cycle and apoptosis assessed by time-lapse microscopy, crystal violet, acridine orange, propidium iodide (PI) and annexin V/PI staining respectively. AQP1 expression was significantly higher in HT-29 than SW480, SW620 and HCT116. Bacopaside II significantly reduced growth at ≥20 µM for HT-29 and ≥15 µM for SW480, SW620 and HCT116. Inhibition of HT-29 at 20 µM was primarily mediated by G0/G1 cell cycle arrest, and at 30 µM by G2/M arrest and apoptosis. Inhibition of SW480, SW620 and HCT116 at ≥15 µM was mediated by G2/M arrest and apoptosis. These results are the first to show that bacopaside II inhibits colon cancer cell growth by inducing cell cycle arrest and apoptosis.

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Section: Introductionmentioning

confidence: 99%

The Purified Extract from the Medicinal Plant Bacopa monnieri, Bacopaside II, Inhibits Growth of Colon Cancer Cells In Vitro by Inducing Cell Cycle Arrest and Apoptosis

Smith

Palethorpe

Tomita

et al. 2018

Cells

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“…The cytotoxicity of BM whole plant extract and Bacoside A towards normal cell line, in our experiments, were identified to be insignificant at a dose 100 μg/ml and 6–8 μg/ml, respectively (Patil et al, 2014; Mallick et al, 2015). However, these dosages were effective in killing the GBM tumor cells.…”

Section: Discussionmentioning

confidence: 68%

“…The mouse and human subjects are found to be tolerant to much higher doses of this compound, which is nearly 300–350 mg per day for 3–6 months, respectively (Nathan et al, 2001; Morgan and Stevens, 2010; Majumdar et al, 2013; Yadav and Reddy, 2013). Bacoside A has also been shown to be anti-tumorigenic in breast, prostate and lung tumor cultures and in animal models (Janani et al, 2010; Prakash et al, 2011; Patil et al, 2014; Mallick et al, 2015), however its mechanisms of action involving differential and specific tumor cell death vs. normal cells had remained unclear. Our mechanism-based study suggests that BM or Bacoside A can be safely administered in the suggested concentrations for GBM specific cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

“…However, bacopa and bacoside A which enhance CaMK2A phosphorylation, are also demonstrated to exert excellent cytotoxic effects on breast cancer cells, in hepatocarcinogenesis etc. (Janani et al, 2010; Prakash et al, 2011; Nandagaon and Kulkarni, 2013; Yadav and Reddy, 2013; Jose et al, 2014; Patil et al, 2014; Mallick et al, 2015). Hence, these reports overall suggest that disturbances in the homeostatic levels of phospho CaMK2A (either by inhibition or via enhancement) may turn tumor cell vulnerable to death.…”

Section: Introductionmentioning

confidence: 99%

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Bacoside A Induces Tumor Cell Death in Human Glioblastoma Cell Lines through Catastrophic Macropinocytosis

Sivakumar

Mishra

2017

Front. Mol. Neurosci.

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Glioblastoma multiforme (GBM) is a highly aggressive type of brain tumor with an extremely poor prognosis. Recent evidences have shown that the “biomechanical imbalances” induced in GBM patient-derived glioblastoma cells (GC) and in vivo via the administration of synthetic small molecules, may effectively inhibit disease progression and prolong survival of GBM animal models. This novel concept associated with de novo anti-GBM drug development has however suffered obstacles in adequate clinical utility due to the appearance of unrelated toxicity in the prolonged therapeutic windows. Here, we took a “drug repurposing approach” to trigger similar physico-chemical disturbances in the GBM tumor cells, wherein, the candidate therapeutic agent has been previously well established for its neuro-protective roles, safety, efficacy, prolonged tolerance and excellent brain bioavailability in human subjects and mouse models. In this study, we show that the extracts of an Indian traditional medicinal plant Bacopa monnieri (BM) and its bioactive component Bacoside A can generate dosage associated tumor specific disturbances in the hydrostatic pressure balance of the cell via a mechanism involving excessive phosphorylation of calcium/calmodulin-dependent protein kinase IIA (CaMKIIA/CaMK2A) enzyme that is further involved in the release of calcium from the smooth endoplasmic reticular networks. High intracellular calcium stimulated massive macropinocytotic extracellular fluid intake causing cell hypertrophy in the initial stages, excessive macropinosome enlargement and fluid accumulation associated organellar congestion, cell swelling, cell rounding and membrane rupture of glioblastoma cells; with all these events culminating into a non-apoptotic, physical non-homeostasis associated glioblastoma tumor cell death. These results identify glioblastoma tumor cells to be a specific target of the tested herbal medicine and therefore can be exploited as a safe anti-GBM therapeutic.

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“…The plant Bacopa monnieri (BM) (L.), a traditional Ayurvedic plant, used for centuries as a memory enhancing, anti-inflammatory, antipyretic, sedative, antiepileptic agents,[ 4 ] nervine tonic, anti-tumor agent, anti-Parkinson's agent,[ 5 ] cardiotonic agent, protective effect, anti-Alzheimer's drug, hepatoprotective agent, antimicrobial agent, and adaptogenic agent. [ 6 ] It is found in wetlands throughout the Indian subcontinent and locally known as Brahmi or Jalanimba. Antioxidant properties of Bacopa may postulate protection from free radical damage in cardiovascular disorder and certain types of cancer.…”

Section: Introductionmentioning

confidence: 99%

Exploring the cytotoxic potential of triterpenoids-enriched fraction of Bacopa monnieri by implementing In vitro, In vivo, and In silico approaches

Mallick¹,

Khan²,

Parveen³

et al. 2017

Phcog Mag

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Background:Bacopa monnieri (BM) is a herbaceous plant traditionally used from time immemorial in Ayurvedic and folklore medicines. We hypothesized that the extract of the whole plant might contain numerous molecules with having antitumor activities that could be very effective in killing of human cancer cells.Objectives:This work investigated anticancer activity of bioactive fraction of BM.Materials and Methods:The hydroalcoholic extract of BM was fractionated with different solvent, namely, hexane, dichloromethane (DCM), acetone, methanol, and water. The in vitro anticancer activity was performed against various Human Cancer Cell lines, namely, Colon (HT29, Colo320, and Caco2), Lung (A549), Cervix (HeLa, SiHa), and Breast (MCF-7, MDAMB-231). Further, DCM fraction was evaluated in vivo for anticancer activity against Ehrlich ascites carcinoma (EAC) tumor-bearing mice since it showed the best cytotoxicity at 72 h (IC50 41.0–60.0 µg/mL). The metabolic fingerprinting of these extract were carried out using high-performance thin-layer chromatography along with quantification of bacoside A, bacoside B, cucurbitacin B, cucurbitacin E, and bittulinic acid.Results:Oral administration of DCM fraction at a dose of 40 mg/kg rendered prominent reduction of tumor regression parameters such as tumor weight, packed cell volume, tumor volume and viable tumor cell count as compared to the untreated mice of the EAC control group. The anticancer activity of DCM fraction may be due to the presence of large amount of bacoside A, B and cucurbitacins. The molecular docking studies of major metabolites with targeted proteins predicted the anticancer activity of DCM fraction which was in support of in vivo activity.Conclusion:The in vitro, in vivo, analytical and in silico studies on DCM fraction of Bacopa monieri has proved its great potential for development of anticancer phytopharmaceuticals.SUMMARY A new HPTLC method has been developed and validated for the qualitative and quantitative analysis of bacoside A, B, cucurbitacin B, D, E and bittulinic acid in Bacopa monnieri extract. Enrichment of active anticancer metabolites was done by polarity based fractionations of hydroalcoholic extract of Bacopa. DCM fraction of a hydroalcoholic extract of Bacopa showed anticancer potential against human cancer cell line (IC50 41.0-60.0 µg/mL) and in EAC treated mice (at a dose of 40 mg/kg body weight). The anticancer activity of Bacopa may be due to the presence of bacosides and cucurbitacin and it was confirmed by in silico screening. Abbreviations used: DBM: DCM fraction of Bacopa monnieri; DCM: Dichloromethane; EAC: Ehrlich ascites carcinoma; HCT: Hematocrit; HGB: Hemoglobin; HPTLC: High performance thin layer chromatography; ICH: International council for Harmonisation; LOD: Limit of detection; LOQ: Limit of quantification; LYM: Lymphocytes; MCH: Mean corpuscular hemoglobin; MCHC: Mean corpuscular haemoglobin concentration (MCHC); MCV: Mean corpuscular volume; MTT: 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PLT: Platelet;...

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Evaluation of anticancer potential of Bacopa monnieri L. against MCF-7 and MDA-MB 231 cell line

Cited by 25 publications

References 13 publications

The Purified Extract from the Medicinal Plant Bacopa monnieri, Bacopaside II, Inhibits Growth of Colon Cancer Cells In Vitro by Inducing Cell Cycle Arrest and Apoptosis

The Purified Extract from the Medicinal Plant Bacopa monnieri, Bacopaside II, Inhibits Growth of Colon Cancer Cells In Vitro by Inducing Cell Cycle Arrest and Apoptosis

Bacoside A Induces Tumor Cell Death in Human Glioblastoma Cell Lines through Catastrophic Macropinocytosis

Exploring the cytotoxic potential of triterpenoids-enriched fraction of Bacopa monnieri by implementing In vitro, In vivo, and In silico approaches

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