Anticancer Activity of Guggulsterone in Human Leukemic Cells
Date
2020-06Metadata
Show full item recordAbstract
Leukemia is a group of blood cancers that is characterized by the uncontrolled
proliferation of hematopoietic cells and their progressive accumulation within the bone
marrow (BM) and secondary lymphoid tissues. The main cause of leukemia remains
unclear, with a combination of genetic and environmental factors involved. Current
treatment options have several limitations with major side effects, mainly related to
high toxicity. In that respect, alternative forms of treatment are required to effectively
manage and treat leukemia patients. Natural products have been shown to effectively
treat several types of human cancers. These natural products include plants and other
natural substances. Once natural product that has shown promising anti-cancer
properties and has been found to possess cancer chemopreventive and therapeutic
potential in a number of cancer cell lines is the plant polyphenol Guggulsterone (GS),
which is extracted from the gum resin of the commiphora mukul tree. Nevertheless, to
date, few studies have investigated the effects of GS in the treatment of leukemia. In
this respect, this study focuses on the efficiency of GS in the treatment of leukemia. In
this study, we demonstrated that guggulsterone inhibited the viability of human
leukemia cells by inducing apoptosis through activation of the intrinsic mitochondrial
pathway. Anti-tumour activity of guggusterone has been found to be associated with
activation of caspase cascade, upregulation of the proapoptotic proteins (Bax and Bid)
and downregulation of the antiapoptotic proteins (Bcl-2, Bcl-xL, xIAP, cIAP-1, cIAP-
2 and survivin). Furthermore, guggulsterone was found to regulate STAT3 signalingpathway. Another specific objective of this study was to exploit the anticancer potential
of guggulsterone in combination with the existing chemotherapeutic approved platinum
drug cisplatin. Our results revealed that guggulsterone acts synergistically with
cisplatin to inhibit the viability of leukemia cells and improved the chemosensitivity of
cisplatin. Our results demonstrate that guggulsterone could serve as a potent natural
anti-cancer agent that may serve as a promising effective treatment option for leukemia
alone or in combination therapies. Our findings serve as a basis for investigating novel
regimens to prevent or delay the development of platinum resistance and overall
improve the treatment of leukemia.
DOI/handle
http://hdl.handle.net/10576/15222Collections
- Biomedical Sciences [64 items ]