Targeting aloe active compounds to c-KIT promoter G-quadruplex and comparative study of their anti proliferative property

Abstract

Small molecules targeting G-quadruplex of oncogene promoter is considered as a promising anticancer therapeutics approach. Natural aloe compounds aloe emodin, and its glycoside derivative aloe emodin-8-glucoside and aloin have anticancer activity and also have potential DNA binding ability. These three compounds have promising binding ability towards quadruplex structures particularly c-KIT G-quadruplex. Here, this study demonstrates complete biophysical study of these compounds to c-KIT quadruplex structure. Aloe emodin showed highest binding stabilization with c-KIT which has been proved by absorbance, fluorescence, dye displacement, ITC and SPR studies. Moreover, comparative study of these compounds with HCT 116 cells line also agreed to their anti proliferative property which may be helpful to establish these aloe compounds as potential anticancer drugs. This study comprises a complete biophysical study along with their anti proliferative property and demonstrates aloe emodin as a potent c-KIT binding molecule.

Graphical Abstract

Communicated by Ramaswamy H. Sarma

Keywords:

• c-KIT quadruplex
• aloe active compounds
• biophysical study
• anti proliferative property

Entry for the table of contents

Aloe vera extracted natural anthraquninone such as aloe emodin, aloin and aloe emodin-8-glucoside have DNA binding ability more specifically G-quadruplex binding property. Biophysical investigation on binding of aloe compounds with c-KIT quadruplex has established aloe emodin as the most potent c-KIT binder among these three natural anthraquinone which is also correlated with their anti proliferative property.

Disclosure statement

There are no conflicts of interest to declare.

Authors contribution

A. Das has designed and carried out the research experiments. A. Das, J. Chakraborty and S. Banerjee have contributed to MTT and FACS study. S. Luikham and J. Bhattacharyya have done the molecular docking study. A. Das and S. Dutta. have contributed to writing of the manuscript.

Additional information

Funding

Authors acknowledge Department of Science and Technology for supporting this work by grants of DST Women Scientists Scheme WOS-A (file no. SR/WOS-A/CS-34/2017(G) and DST SERB (Grant no. EMR/2017/000659). We also acknowledge the Director, CSIR-IICB for laboratory facilities.