Evaluation of the cytotoxic effect of the monoterpene indole alkaloid echitamine in-vitro and in tumour-bearing mice

Jagetia, Ganesh Chandra; Baliga, Manjeshwar Shrinath; Venkatesh, Ponemone; Ulloor, Jagadish; Mantena, Sudheer K.; Genebriera, Joseph; Mathuram, V.

doi:10.1211/jpp.57.9.0017

Cited by 35 publications

(14 citation statements)

References 20 publications

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“…[2] As a result, scientists have investigated the pharmacological effects of akuammiline alkaloids and discovered their wide range of biological properties, which span from anticancer to analgesic effects. For example, (À)-echitamine (1), which was first isolated in 1875, [3] displays both in vitro and in vivo cytotoxicity, [4] whereas (+)-strictamine (2) [5] inhibits the transcription factor NF-kB ( Figure 2). [6] Additionally, derivatives of (+)-picraline (3) [7] inhibit the renal cortex protein SGLT2, [8] while (À)-aspidophylline A [(À)-4] reverses drug resistance in cancerous cell lines.…”

Section: Introductionmentioning

confidence: 99%

Cascade Reactions: A Driving Force in Akuammiline Alkaloid Total Synthesis

et al. 2014

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The akuammiline alkaloids are a family of intricate natural products which have received considerable attention from scientists worldwide. Despite the fact that many members of this alkaloid class were discovered over 50 years ago, synthetic chemistry has been unable to address their architectures until recently. This minireview provides a brief overview of the rich history of the akuammiline alkaloids, including their isolation, structural features, biological activity, and proposed biosyntheses. Furthermore, several recently completed total syntheses are discussed in detail. These examples not only serve to highlight modern achievements in alkaloid total synthesis, but also demonstrate how the molecular scaffolds of the akuammilines have provided inspiration for the discovery and implementation of innovative cascade reactions for the rapid assembly of complex structures.

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Section: Introductionmentioning

confidence: 99%

Cascade Reactions: A Driving Force in Akuammiline Alkaloid Total Synthesis

et al. 2014

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“…Similarly, other antineoplastic agents like, doxorubicin, vinblastine, taxol and teniposide (VM-26) have been reported to induce cytotoxicity in V79 cells [11,[39][40][41][42]. Treatment of HeLa, MCF-7, HL 60, or KB cells to alcoholic extract of the stem bark of Alstonia scholaris or echitamine chloride have been reported to induce cytotoxicity earlier [8,20,43,44]. The cytotoxic effect of APE is reflected in proliferation indecies (PI), where a concentration dependent reduction in PI was observed at all post-treatment times in cells treated with various concentrations of APE.…”

Section: Discussionmentioning

confidence: 99%

Determination of Antineoplastic Activity of Rohituka, Aphanamixis Polystachya (Wall) RN Parker in Hela Cells: Correlation with Clonogenicity and DNA Damage

Jagetia

Venkatesha

2016

IJCAM

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The antineoplastic activity of chloroform stem bark extract of rohituka, Aphanamixis polystachya (APE) used traditionally to treat spleen and liver tumors was evaluated in cultured HeLa cells by clonogenic and micronucleus assays. Treatment of HeLa cells with 0, 5, 10, 25, 50, 75 or 100µg/ml APE for different times caused a concentration-dependent reduction in the cell survival up to 6 h post-treatment (p<0.005) followed by a non-significant decline in the cells treated with APE for 24 h. Therefore, 6h treatment time was considered as an optimum time for APE exposure and further studies were carried out using this treatment time. Exposure of HeLa cells to different concentrations of APE resulted in a concentration-dependent decline in the cell viability and 100µg/ ml APE resulted in 72% cell death when compared with the non-drug treated control group. These results were further confirmed by clonogenic assay where, APE treatment caused a concentration-dependent decline in the clonogenicity of HeLa cells, and the surviving fraction of cells was reduced to 0.22 after treatment with 100µg/ml APE, the highest concentration screened. The inhibitory concentration (IC50) of APE was found to be 25µg/ml. The APE-induced DNA damage was estimated by micronucleus assay, where the treatment of HeLa cells with various concentrations of APE resulted in a concentration-dependent rise in the frequency of micronuclei in binucleate HeLa cells (MNBNCs) at 20, 30, and 40 h post-treatment. This increase in MNBNCs was significantly higher than the baseline frequency of MNBNCs. APE treatment also increased the frequency of HeLa cells bearing more than one micronucleus (MN) indicating higher degree of DNA damage. The frequency of MNBNC increased with scoring time and a maximum elevation in the MNBNC frequency was observed at 30 h posttreatment. The MNBNC induction and clonogenicity of HeLa cells was inversely related indicating that increased MNBNC formation resulted in a corresponding reduction in the cell survival. The cell proliferation indices (PI) declined with increasing concentration of APE that increased with screening time. Our study demonstrates that APE is able to kill HeLa cells effectively and this cell killing effect of APE may be due its ability to induce DNA damage.

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“…Out of the thirteen indole alkaloids isolated from the root bark of sister species A. macrophylla, the pronounced cytotoxic activity has been found for bisindoles O-acetylmacralstonine, villalstonine and macrocarpamine against the human cancer cell lines, MOR-P (adenocarcinoma), COR-L23 (large cell carcinoma), StMI1 1a (melanoma), Caki-2 (renal cell carcinoma), MCF7 (breast adenocarcinoma) and LS174T (colon adenocarcinoma) [55]. The alkaloid echitamine, present in the stem bark of A. scholaris has been reported to be cytotoxic in vitro and in vivo [56].…”

Section: Issn: 2470-1017mentioning

confidence: 99%

“…Echitamine chloride, one of the constituent of ASE has been reported to inhibit DNA synthesis [60][61]. Our earlier study has indicated that presence of echitamine chloride in ASE and its cytotoxic effects in vitro and in vivo [56]. It may also have acted by inhibiting serine proteases.…”

Section: Issn: 2470-1017mentioning

confidence: 99%

Short - Term Loosen Up Meditation Induced EEG and Autonomic Response in Healthy Japanese Students

Iwakuma¹,

Nakayama²,

Oshita³

2016

J Alt Med Res

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Back ground: Cancer has emerged as the second largest killer disease in the world and mortality rates for solid tumors remain unchanged. Therefore there is need to screen, new remedies to treat cancer. Materials and methods:The antineoplastic activity of different doses of hydroalcoholic extract of Alstonia scholaris (L.) R. Br. (ASE) was studied in Swiss albino mice, transplanted with Ehrlich Ascites Carcinoma cells (EAC) in its peritoneal cavity. The effect of ASE injected at different stages of tumor development was evaluated by studying tumor free survivors. In another study EAC cells were treated with Echitamine Chloride (ECL) in vitro and transplanted back into mice and tumor free survivors determined. The glutathione and lipid peroxidation were also measured after ASE treatment. Results:The daily administration of ASE in tumor bearing mice caused a dose-dependent remission of tumor, and highest regression was observed at 480 mg/kg b. wt. this dose showed some toxic effects and next lower dose i.e. 420 mg/kg was considered as the suitable dose, where 33.33% of the animals survived up to 120 days post-tumor-cell inoculation, as against no survivors in the saline treated control and positive cyclophosphamide treated groups. The ASE caused a dosedependent elevation in the median survival time (MST) and average survival time (AST), causing a corresponding increase in the median life span (IMLS) and average life span (IALS) of experimental animals. Treatment of EAC mice with 420 mg/kg ASE also retarded tumor development even during the late stages of tumor development, while cyclophosphamide was completely ineffective. The in vitro treatment of EAC cells with ASE or ECL and their transplantation in mice showed that ASE treatment was more potent than ECL treatment as evident by increased MST and AST in the former when compared with the latter. Assay of glutathione and lipid peroxidation after 240, 420 mg/kg ASE or 25 mg/kg cyclophosphamide led to a decline in glutathione contents and increase in lipid peroxidation. Conclusions:Our study shows that ASE treatment kills the tumor cells effectively increasing long-term disease free survival of experimental mice, which may be due to reduced glutathione and increased lipid peroxidation.

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Evaluation of the cytotoxic effect of the monoterpene indole alkaloid echitamine in-vitro and in tumour-bearing mice

Cited by 35 publications

References 20 publications

Cascade Reactions: A Driving Force in Akuammiline Alkaloid Total Synthesis

Cascade Reactions: A Driving Force in Akuammiline Alkaloid Total Synthesis

Determination of Antineoplastic Activity of Rohituka, Aphanamixis Polystachya (Wall) RN Parker in Hela Cells: Correlation with Clonogenicity and DNA Damage

Short - Term Loosen Up Meditation Induced EEG and Autonomic Response in Healthy Japanese Students

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