Iridoid glycosides-Kutkin, Picroside I, and Kutkoside from Picrorrhiza kurroa Benth inhibits the invasion and migration of MCF-7 breast cancer cells through the down regulation of matrix metalloproteinases

Rathee, Dharmender; Madhavi, Thanki; Bhuva, Satish; Anandjiwala, Sheetal; Agrawal, Reena

doi:10.1016/j.arabjc.2011.01.011

Cited by 45 publications

(22 citation statements)

References 44 publications

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“…The DCM fraction (IC 50 ranging from 36 to 51 μ g mL −1 at 72 h) showed best cytotoxic activities towards all cancer cell lines (Figures 3 and 4(a) – 4(d) ). The best cytotoxic activity of DCM fraction from P. kurroa may be attributed to the presence or synergistic activities of phytochemical components including sterol, triterpenes, and polyphenols [ 18 , 20 , 22 – 34 ]. However, betulinic acid may be attributed to this activity [ 41 ], since DCM fraction is rich in it, as proved by our analytical studies.…”

Section: Resultsmentioning

confidence: 99%

“…In brief, MTT [3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide] assay was performed on MCF-7, SiHa, HeLa, and MDA-MB 231 cell lines [ 34 ]. 1 × 10 4 cells were seeded on 96-well plates supplemented with 100 μ L of the respective culture media for a period of 24 h at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…HPTLC fingerprints of mother extracts and their fractions like hexane, DCM, n-butanol, acetone, methanol, and water were carried out for their quality control and determination of number of compounds present in them. Presence of picrosides [ 15 – 17 ], cucurbitacins [ 18 – 20 ], apocynin [ 21 ], and their anticancer potential [ 18 , 20 , 22 – 34 ] has already been reported and hence simultaneous analysis of these compounds in the BAF was carried out using newly developed HPTLC methods. These methods were developed as per ICH guidelines, similar to several methods reported by the Laboratory for Quality Control of Herbal Drugs and Botanicals [ 35 , 36 ].…”

Section: Methodsmentioning

confidence: 99%

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HPTLC Analysis of Bioactivity Guided Anticancer Enriched Fraction of Hydroalcoholic Extract ofPicrorhiza kurroa

Mallick

Singh

Parveen

et al. 2015

BioMed Research International

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Objective. Hydroalcoholic extract of Picrorhiza kurroa and its fractions were subjected to in vitro screening for cytotoxicity; further best active fraction (BAF) obtained was tested against Ehrlich ascites carcinoma (EAC) model in Balb/c mice after its quality control analysis. Methods. Cytotoxicities of all the fractions and mother extract of P. kurroa were determined, using MTT assay on breast cancer (MCF-7, MDA-MB 231) and cervical cancer (HeLa, SiHa) cell lines. Metabolic fingerprinting was developed using HPTLC with quantification of biomarkers (cucurbitacins B and E; betulinic acid; picrosides 1 and 2; and apocynin) in BAF. The EAC tumor-bearing mice were used for in vivo anticancer activity after oral administration (50 mg Kg−1) for 10 days. Results. Cytotoxicity assay of mother extract and its fractions over breast cancer and cervix cancer cell lines showed that dichloromethane (DCM) fraction was most cytotoxic (IC50 36.0–51.0 µg mL−1 at 72 h). Oral administration of DCM fraction showed significant reduction in tumor regression parameters, viable tumor cell count and restoration of hematological parameters may be due to presence of cucurbitacins B and E; betulinic acid; picrosides 1 and 2; and apocynin, as compared to the untreated mice of the control group. Conclusion. The DCM fraction of P. kurroa displayed potent anticancer activity and can be further explored for the development of a potential candidate for cancer therapy.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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HPTLC Analysis of Bioactivity Guided Anticancer Enriched Fraction of Hydroalcoholic Extract ofPicrorhiza kurroa

Mallick

Singh

Parveen

et al. 2015

BioMed Research International

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“…kurroa having therapeutic importance in several herbal drug formulations [ 3 ]. P-I is reported to be antimicrobial [ 4 ] and used against hepatitis B [ 5 ]. P-II possess different pharmacological activities such as antiapoptotic [ 6 ], neuroprotective [ 7 ], anti-inflammatory [ 8 ], anti-oxidant [ 9 ] and prevents myocardial ischemia reperfusion injury [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

NGS Transcriptomes and Enzyme Inhibitors Unravel Complexity of Picrosides Biosynthesis in Picrorhiza kurroa Royle ex. Benth

et al. 2015

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Picrorhiza kurroa is an important medicinal herb valued for iridoid glycosides, Picroside-I (P-I) and Picroside-II (P-II), which have several pharmacological activities. Genetic interventions for developing a picroside production platform would require knowledge on biosynthetic pathway and key control points, which does not exist as of today. The current study reports that geranyl pyrophosphate (GPP) moiety is mainly contributed by the non-mevalonate (MEP) route, which is further modified to P-I and P-II through phenylpropanoid and iridoid pathways, in total consisting of 41 and 35 enzymatic steps, respectively. The role of the MEP pathway was ascertained through enzyme inhibitors fosmidomycin and mevinolin along with importance of other integrating pathways using glyphosate, aminooxy acetic acid (AOA) and actinomycin D, which overall resulted in 17%-92% inhibition of P-I accumulation. Retrieval of gene sequences for enzymatic steps from NGS transcriptomes and their expression analysis vis-à-vis picrosides content in different tissues/organs showed elevated transcripts for twenty genes, which were further shortlisted to seven key genes, ISPD, DXPS, ISPE, PMK, 2HFD, EPSPS and SK, on the basis of expression analysis between high versus low picrosides content strains of P. kurroa so as to eliminate tissue type/ developmental variations in picrosides contents. The higher expression of the majority of the MEP pathway genes (ISPD, DXPS and ISPE), coupled with higher inhibition of DXPR enzyme by fosmidomycin, suggested that the MEP route contributed to the biosynthesis of P-I in P. kurroa. The outcome of the study is expected to be useful in designing a suitable genetic intervention strategy towards enhanced production of picrosides. Possible key genes contributing to picroside biosynthesis have been identified with potential implications in molecular breeding and metabolic engineering of P. kurroa.

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“…The administration of picroliv caused subsequent amelioration in disease activity index along with the reduction in enhanced myeloperoxidase activity, MDA concentration, and the IL-1b, TNF-a, and NF-jB p65 expressions in dextran sulfate sodium induced ulcerative colitis in mice . Further investigations documented the anticancer potential of picroliv which along with P-I and kutkoside from P. kurroa down-regulated MCF-7 cell lines invasion and migration via reduced matrix metalloproteinases (MMPs) expressions (Rathee et al 2013). …”

Section: Kutkin/picrolivmentioning

confidence: 98%

Biosynthesis and therapeutic implications of iridoid glycosides from Picrorhiza genus: the road ahead

Kumar

Chauhan

Tandon

2016

J. Plant Biochem. Biotechnol.

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Picrorhiza genus is emerging as an important paradigm for herbal drug formulations due to its versatile iridoid glycosides exhibition and robustness in the treatment of diverse infections including hepatic amoebiasis, cancer, malaria, ulcerative colitis and cerebral ischemia reperfusion injury. Owing to the superiority of these bioactivities, iridoid glycosides from Picrorhiza have become a hot research area over the years. A metabolic pathway for the formation of iridoid glycosides has been proposed. However, some enzymes and genes of this route are still unidentified and demand the enumeration of facilitating pathways contributing to the biosynthesis of iridoid glycosides. This review summarizes the current knowledge of all naturally occurring iridoid glycosides from Picrorhiza, their biosynthesis and pharmacological capabilities which could provide the insight into metabolic regulation and the basis for the development of new drugs.

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Iridoid glycosides-Kutkin, Picroside I, and Kutkoside from Picrorrhiza kurroa Benth inhibits the invasion and migration of MCF-7 breast cancer cells through the down regulation of matrix metalloproteinases

Cited by 45 publications

References 44 publications

HPTLC Analysis of Bioactivity Guided Anticancer Enriched Fraction of Hydroalcoholic Extract ofPicrorhiza kurroa

HPTLC Analysis of Bioactivity Guided Anticancer Enriched Fraction of Hydroalcoholic Extract ofPicrorhiza kurroa

NGS Transcriptomes and Enzyme Inhibitors Unravel Complexity of Picrosides Biosynthesis in Picrorhiza kurroa Royle ex. Benth

Biosynthesis and therapeutic implications of iridoid glycosides from Picrorhiza genus: the road ahead

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