Preprint / Version 1

Black pepper and piperine induce anticancer effects on leukemia cell line

Authors

  • Somesh Banerjee Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India
  • Parul Katiyar Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India
  • Vijay Kumar Laboratory of Structural Microbiology, Regional Centre for Biotechnology, Faridabad 121001, Haryana, India
  • Shashank Saini Plant Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India
  • Ritu Varshney Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India
  • Vengadesan Krishnan Laboratory of Structural Microbiology, Regional Centre for Biotechnology, Faridabad 121001, Haryana, India
  • Debabrata Sircar Plant Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India
  • Partha Roy Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India

Keywords:

black pepper, piperine, chronic myeloid leukemia, intrinsic apoptosis pathway, reactive oxygen species

Abstract

The black pepper, most commonly used in Indian cuisines for ages, is considered as “king of spices.” The present study evaluates the anticancer potential of black pepper and its main constituent, i.e. alkaloid piperine, against human leukemia cell line, K-562 cells. Gas chromatography–mass spectrometry (GC–MS) analysis confirmed the presence of piperine in black pepper extract. The methanolic extract of black pepper (BP-M) and pure piperine (PIP) showed a strong cytotoxic effect against this cell line. Both BP-M and PIP generated apoptotic bodies in K-562 cells and caused nuclear condensation as visualized by fluorescent microscopy, which was further confirmed by flow cytometry analysis. BP-M and PIP also generated reactive oxygen species in K-562 cells as established by flow cytometry. The translation of Bax, caspase-3 and caspase-9 genes was found to be upregulated with subsequent downregulation of Bcl-2 gene. The anti-proliferative effect of both BP-M and PIP was also observed by trypan blue staining and was further confirmed by the downregulated expression of proliferating cell nuclear antigen (PCNA). The molecular docking studies showed the binding of PIP with PCNA and Bcl-2 and supported the in vitro findings. The docking studies also proposed the binding of PIP to ADP binding pocket of Apaf-1 protein. Taken together, these findings signify the anticancer potential of both black pepper and PIP, thus proposing black pepper as a potent nutraceutical for preventing the progression of chronic myeloid leukemia. Keywords: black pepper, piperine, chronic myeloid leukemia, intrinsic apoptosis pathway, reactive oxygen species

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