Methyl-β-cyclodextrin, an actin depolymerizer augments the antiproliferative potential of microtubule-targeting agents

Following research was done in collaboration with Prof. Dulal Panda, BSBE IITB.

Methyl-β-cyclodextrin (MCD), an established pharmacological adjuvant enhances the solubility and bioavailability of several small molecules, drugs and nano-particles. It also reduces actin filaments which is one of the cellular cytoskeletal elements. This cytoskeletal filament controls multiple cellular processes such as cell migration, division, cytokinesis and also maintenance of shape and size. It also regulates the plasma membrane permeability in various types of cells. In this work, we have shown that MCD-mediated reduction of actin filaments increases the intracellular accumulation of microtubule-targeting chemotherapeutic drugs by ~50% with respect to the untreated cells by increasing plasma membrane permeability. Hence, critical drug concentration, that leads to the death of cancer cells, can be reached by administrating minimal dosage. We have shown that the combination of MCD and the first line anti-cancer drugs (such as vinblastine and paclitaxel) synergistically inhibits the proliferation of cervical, breast, hepatocellular (liver), prostate cancer cells. This combination also showed promising result on multidrug-resistant breast cancer cells.

Acknowledgement: We acknowledge University Grants Commission, Govt. of India for providing fellowship to NM. We would like to acknowledge the funding provided by Tata Innovation Fellowship from Department of Biotechnology (BT/ HRD/35/01/05/2017) to DP and seed grant from IITB (Grant # 14IRCCSG002) to AM.

Publication details: 

Methyl-β-cyclodextrin, an actin depolymerizer augments the antiproliferative potential of microtubule-targeting agents

Nikita Mundhara 1, Abhijit Majumder 2*, Dulal Panda 1*

  1. Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India. (abhijitm [at] iitb [dot] ac [dot] in)
  2. Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai 400076, India. (panda [at] iitb [dot] ac [dot] in)

Website Link: https://www.nature.com/articles/s41598-019-43947-4