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RETRACTED ARTICLE: Mahanine synergistically enhances cytotoxicity of 5-fluorouracil through ROS-mediated activation of PTEN and p53/p73 in colon carcinoma

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This article was retracted on 28 February 2024

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Abstract

5-Fluorouracil (5-FU) alone or in combination with other drugs is the main basis of chemotherapeutic treatment in colorectal cancer although patients with microsatellite instability generally show resistance to 5-FU treatment. The present investigation is focussed on the mechanistic insight of a pure herbal carbazole alkaloid, mahanine, as a single or in combination with 5-FU in colon cancer. We demonstrated that mahanine-induced apoptosis involved reactive oxygen species (ROS)-mediated nuclear accumulation of PTEN and its interaction with p53/p73. Mahanine and 5-FU in combination exerted synergistic inhibitory effect on cell viability. This combination also enhanced ROS production, increased tumour suppressor proteins and suppressed chemo-migration. Taken together, our results revealed that mahanine can be a potential chemotherapeutic agent with efficacy to reduce the concentration of toxic 5-FU in colon cancer.

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Acknowledgments

This work received financial support from CSIR-IICB, CSIR under IAP-0001, HCP004, NMITLI, TLP-004 and DBT under GAP 235, ICMR, Govt. of India. Dr. Chitra Mandal is grateful to financial support by J.C. Bose Fellowship, DST of Govt. of India and also mutual grant from ICMR and German Cancer Research Centre.

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Authors and Affiliations

  1. Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research (CSIR)-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata, 700032, India

    Ranjita Das, Kaushik Bhattacharya, Sayantani Sarkar, Suman Kumar Samanta & Chitra Mandal

  2. National Institute of Pharmaceutical Education and Research, Kolkata, Kolkata, India

    Bikas C. Pal

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  1. Ranjita Das
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  2. Kaushik Bhattacharya
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Correspondence to Chitra Mandal.

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Supplementary material 1 (DOCX 20 kb)

10495_2013_907_MOESM2_ESM.tif

Supplementary material 2 (TIFF 192 kb) S-1 Effect of mahanine on proliferation of colon cancer cells (SW480) and African green monkey kidney cells (Vero). Cells were treated with mahanine (0-30 μM) and cell proliferation was measured by MTT assay after 48 h. Mahanine-induced growth inhibitory effect was expressed as cell viability, inferred from metabolic activity, relative to untreated controls. Data were represented as  % of cell proliferation (% of MTT conversion relative to untreated control cells). Each value is the mean ± SD of three independent experiments

10495_2013_907_MOESM3_ESM.tif

Supplementary material 3 (TIFF 131 kb) S-2. p53 status in HCT116 (p53wt) and stably knockdown HCT116 (p53null) cells. p53wt and p53null cells were harvested and whole cell protein lysates were prepared for Western blot analysis with indicated antibody

10495_2013_907_MOESM4_ESM.tif

Supplementary material 4 (TIFF 1735 kb) S-3 Effect of 5-FU on cell cycle arrest of HCT116 (p53wt) and HCT116 (p53null) cells. Both the cells were treated with different concentrations of 5-FU for 24 h as indicated and cell cycle analyses were performed by flow cytometry. At lower concentration, 5-FU resulted S phase arrest in respect to untreated cells whereas at higher concentration cells were arrested in G1-S phase

10495_2013_907_MOESM5_ESM.tif

Supplementary material 5 (TIFF 314 kb) S-4. Mahanine induced upregulation of p21 and Bax. HCT116 (p53wt) and HCT116 (p53null) cells were treated with different concentrations of mahanine for 24 h as indicated. The cells were harvested and whole cell protein lysates were prepared for Western blot analysis with indicated antibodies. The presented data have been derived from three different experiments, one of which is shown here

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Das, R., Bhattacharya, K., Sarkar, S. et al. RETRACTED ARTICLE: Mahanine synergistically enhances cytotoxicity of 5-fluorouracil through ROS-mediated activation of PTEN and p53/p73 in colon carcinoma. Apoptosis 19, 149–164 (2014). https://doi.org/10.1007/s10495-013-0907-6

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