BRM270 targets cancer stem cells and augments chemo-sensitivity in cancer

Abstract

Over the past decade, a number of studies have demonstrated the resistance of cancer cells to conventional drugs and have recognized this as a major challenge in cancer therapy. While attempting to understand the underlying mechanisms of chemoresistance, several studies have suggested that the presence of cancer stem cells (CSCs) in tumors is one of the major pathways contributing toward resistance. Chemoresistance leads to cancer treatment failure and worsens the prognosis of patients. Natural herbal compounds are gaining attention as an alternative treatment strategy for cancer. These compounds may be effective against chemoresistant cells either alone or synergistically alongside conventional drugs, sensitizing cancer cells and enhancing the therapeutic efficacy. BRM270 is a natural compound made from seven herbal plant (Saururus chinensis, Citrus unshiu Markovich, Aloe vera, Arnebia euchroma, Portulaca oleracea, Prunella vulgaris var. lilacina and Scutellaria bacicalensis) extracts used in Asian traditional medicine and has the potential to target CSCs. Several studies have demonstrated the positive effects of BRM270 against chemoresistant cancer and its synergy alongside existing cancer drugs, including paclitaxel and gefitinib. These effects have been observed against various cancer types, including resistant non-small cell lung cancer (NSCLC), glioblastoma, multi-drug resistant osteosarcoma, cervical cancer, pancreatic cancer and hepatocarcinoma. The present review discusses the effects of BRM270 treatment against CSC-associated chemoresistance in common types of cancer.

Keywords: BRM270; cancer stem cell; chemoresistance; multi-drug resistant; natural compound; non-small cell lung cancer.

Figure 1.

BRM270 consists of seven medicinal plant extracts. Saururus chinensis, Citrus unshiu Markovish, Aloe vera, Arnebia euchroma, Portulaca oleracea, Prunella vulgaris var. lilacina and Scutellaria baicalensis are the seven medicinal plants used in the BRM270 formulation.

Figure 2.

BRM270 acts against chemoresistance by inhibiting CSCs. BRM270 impacts gefitinib- and paclitaxel-resistant (A) NSCLC, (B) cervical cancer, (C) glioblastoma, (D) pancreatic cancer, and (E) multi-drug resistant osteosarcoma to overcome chemoresistance through the inhibition of CSC populations and stem-like characteristics. The CSC phenotype is one of the major underlying mechanisms in the chemoresistance of cancer cells. CSC, cancer stem cell; CC, cervical cancer; NSCLC, non-small cell lung cancer; VEGF, vascular endothelial growth factor; EMT, epithelial-mesenchymal transition; GBM, glioblastoma multiforme; CCRT, concurrent chemoradiotherapy; miR, microRNA; SOX2, SRY (sex determining region Y)-box 2.

Figure 3.

BRM270 suppresses inflammation-induced hepatocarcinogenesis by targeting the IL-6/STAT3/COX-2 axis. BRM270-induced PMA inhibits the phosphorylation of STAT3 at the tyrosine 705 site, thereby inhibiting IL-6 and COX-2 expression. IL-6 and COX-2 are essential for tumor growth and inflammation-induced hepatocarcinogenesis. BRM270 also inhibits cell metastasis via the suppression of COX-2 and the reduction of EMT and cell mobility. PMA, phorbal-12-myristate-13-acetate; EMT, epithelial-mesenchymal transition; IL-6, interleukin 6; E/N-Cad, E/N-cadherin; COX-2, cyclooxygenase-2; MMP-9, matrix metallopeptidase 9.