Anticancer Activity of Guggulsterone in Human Leukemic Cells

Abstract

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.