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Combinatorial Effect of Arsenic and Herbal Compounds in Telomerase-Mediated Apoptosis Induction in Liver Cancer

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Abstract

Tumour illness and its resistance against existing anticancer therapies pose a serious health concern globally despite the progressive advancement of therapeutic options. The prevailing treatment of HCC using numerous antitumor agents has inflated long-lived complete remissions, but a percentage of individuals still die due to disease recurrence, indicating a need for further exploration of possible anti-tumour regimes. We aim to boost the effectiveness of the HCC treatment by conducting current investigations evaluating the effect of arsenic trioxide (ATO) with different herbal compounds like quercetin and aloe-emodin against liver tumour via inhibition of telomerase, a pro-cancer enzyme. The anticancer activity of ATO with herbal compounds was investigated in human control liver cell line (Wrl-68) and cancer liver cell line (HepG2) at different time intervals. Viability and cytotoxicity in response to combinatorial drugs were assessed in vitro by trypan blue dye exclusion assay and MTT and WST assay. Apoptosis was analysed by annexin V/PI assay, and the expression of telomerase and apoptosis-regulating proteins was evaluated by immunoblotting and qRT-PCR. Arsenic trioxide in combination with quercetin and aloe-emodin reduced cell viability in cancerous cells compared to normal cells by inducing apoptosis, downregulating telomerase and Bcl-2 (anti-apoptotic protein) and upregulating the expression of Bax (pro-apoptotic protein). ATO exhibited significant anticancer effects due to the synergistic effects of quercetin and aloe-emodin in liver tumour cells. The current study data collectively suggest that a successful inhibition of cancer growth by the combination of ATO and tested herbal medicines against liver tumour growth is via the inhibition of telomerase activity.

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The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

The work was supported by grant No. EMR/2017/004171 from DST-SERB (Science and Engineering Research Board) India and the Council of Scientific and Industrial Research (CSIR-UGC) in the form of a fellowship to the first author.

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Authors and Affiliations

  1. Department of Biotechnology, School of Earth Biological and Environmental Sciences, Central University of South Bihar, Gaya, Bihar, India

    Archana Chaudhary, Sadhan Kumar Bhardwaj & Rizwanul Haque

  2. Department of Life Sciences, School of Earth Biological and Environmental Sciences, Central University of South Bihar, Gaya, Bihar, India

    Azmi Khan & Amrita Srivastava

  3. Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Hajipur, Bihar, India

    Kislay Kumar Sinha

  4. Toxicology Invivotek, Genesis Biotech Company Hamilton, Hamilton Township, NJ, 08691, USA

    Mehboob Ali

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  1. Archana Chaudhary
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Contributions

Rizwanul Haque contributed to the study conception and design. Material preparation and data collection were performed by Archana Chaudhary. Formal analysis and investigation were carried out by Archana Chaudhary, Sadhan Kumar Bhardwaj, Azmi Khan, Amrita Srivastava, Kislay Kumar Sinha, Mehboob Ali and Rizwanul Haque. Archana Chaudhary, Sadhan Kumar Bhardwaj and Azmi Khan drafted the manuscript. Rizwanul Haque and Mehboob Ali reviewed and edited the previous version of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Rizwanul Haque.

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Chaudhary, A., Bhardwaj, S.K., Khan, A. et al. Combinatorial Effect of Arsenic and Herbal Compounds in Telomerase-Mediated Apoptosis Induction in Liver Cancer. Biol Trace Elem Res 201, 3300–3310 (2023). https://doi.org/10.1007/s12011-022-03430-0

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