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      https://www.ias.ac.in/article/fulltext/jbsc/045/0097

    • Keywords

       

      DKK4; doxorubicin; drug sensitivity; glucose; P-gp; ROS; sorafenib

    • Abstract

       

      Altered glucose uptake and metabolism is the key characteristic of cancer cells including hepatocellularcarcinoma (HCC). However, role of glucose availability in chemotherapeutic outcome of HCC is unclear. Thepresent study investigates the effect of glucose facilitated sensitization of HCC cells towards doxorubicin(DOX) and sorafenib (SORA). In HCC cells, we observed that hyperglycemic culture condition (HG) isassociated with increased sensitivity towards DOX and SORA. P-glycoprotein (P-gp), a transporter involved indrug efflux, was elevated in HCC cells in NG, rendering them less susceptible to DOX and SORA. Further, thisstudy demonstrated that knockdown of dickkopf protein 4 (DKK4), a Wnt antagonist protein, causes enhancedglucose uptake and reduction in P-gp level rendering HCC cells in NG sensitive to DOX and SORA.Moreover, HG elevates the level of intracellular reactive oxygen species (ROS), which regulates P-gp.Alteration in intracellular ROS did not directly affect regulation of DKK4 in HCC cells. Functional assayssuggest that alterations in DKK4 and P-gp level in HCC cells are dependent on glucose availability andchanges in ROS level because of enhanced glucose utilization, respectively. Collectively, the present studyhighlights direct involvement of glucose-induced ROS, DKK4 and P-gp in altering the sensitivity of HCC cellstowards DOX and SORA.

    • Author Affiliations

       

      SURBHI CHOUHAN1 SNAHLATA SINGH1 DIPTI ATHAVALE1 PRANAY RAMTEKE1 MURALIDHARAN VANUOPADATH2 BIPIN G NAIR2 SUDARSLAL SADASIVAN NAIR2 MANOJ KUMAR BHAT1

      1. National Centre for Cell Science, Savitribai Phule Pune University Campus, Pune 411 007, India
      2. Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Clappana P.O, Kollam 690 525, India
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