Demethoxycurcumin: A naturally occurring curcumin analogue with antitumor properties

Abstract

The eradication of cancer in a patient remains an elusive challenge despite advances in early detection and diagnosis, chemo- and immunotherapy, pinpoint radiation treatments, and expert surgical intervention. Although significant gains have been made in our understanding of cancer cell biology, a definite cure for most cancers does not exist at present. Thus, it is not surprising that the research and medical communities continue to explore the importance and therapeutic potential of natural products in their multimodality cancer treatment approach. Curcuminoids found in turmeric are one such class of natural products that have been extensively investigated for their potential to halt the progression of cancer cell proliferation and, more important, to stop metastasis from occurring. In this review, we examine one curcuminoid (demethoxycurcumin [DMC]) largely because of its increased stability and better aqueous solubility at physiological pH, unlike the more well-known curcuminoid (curcumin), which is largely unabsorbed after oral ingestion. The present review will focus on the signaling pathways that DMC utilizes to modulate the growth, invasion, and metastasis of cancer cells in an effort to provide enhanced mechanistic insight into DMC's action as it pertains to brain, ovarian, breast, lung, skin, and prostate cancer. Additionally, this review will attempt to provide an overview of DMC's mechanism of action by modulating apoptosis, cell cycle, angiogenesis, metastasis, and chemosensitivity. Lastly, it is hoped that increased understanding will be gained concerning DMC's interactive role with microRNA-551a, 5' adenosine monophosphate-activated protein kinase, nuclear factor-κB, Wnt inhibitory factor-1, and heat shock protein 70 to affect the progression of cancer.

The Curcumin Analogue, EF-24, Triggers p38 MAPK-Mediated Apoptotic Cell Death via Inducing PP2A-Modulated ERK Deactivation in Human Acute Myeloid Leukemia Cells

“…However, few of those clinical trials showed positive outcomes [7], mainly due to its low solubility and poor bioavailability (<1%) [8]. Demethoxycurcumin (DMC) and diphenyl difluoroketone (EF-24) are natural and synthetic CUR analogues, respectively, that display multiple potent bioactivities and increased bioavailability compared to CUR [9,10]. For example, EF-24 was reported to have higher oral bioavailability (60%) and to be much safer than a chemotherapeutic drug in mice [11,12].…”

“…In addition, EF-24 exhibited a 10~20-fold lower 50% growth inhibitory concentration (IC 50 ) than CUR in various solid tumor cells including ovarian, cervical, lung, breast, and prostate cancer cells [13][14][15][16]. Although these two CUR analogues, EF-24 and DMC, were reported to inhibit the proliferation of various solid tumor cells in in vitro and in vivo models [9,10], the precise impacts of these analogues on non-solid tumors, particularly AML, are still unclear.…”

Demethoxycurcumin: A naturally occurring curcumin analogue for treating non‐cancerous diseases

“…Therefore, it would appear appropriate to investigate the therapeutic potential of DMC for adjunctive treatment of various diseases (R. Li et al, ; Quitschke, ). We have recently reviewed the promising antitumor effects of DMC that are, in some cases, even greater than those of curcumin (Hatamipour et al, ). Here, our aim was to review the biological and pharmacological activity of DMC relevant to the treatment of noncancerous diseases.…”

Dual Targeting of the p38 MAPK-HO-1 Axis and cIAP1/XIAP by Demethoxycurcumin Triggers Caspase-Mediated Apoptotic Cell Death in Oral Squamous Cell Carcinoma Cells

“…In contrast, CUR was also reported to act as an iron chelator to interfere with ferritin expression and induce the apoptosis of prostate cancer cells [51]. Furthermore, the in vivo anticancer activities of DMC have been documented in a xenograft brain tumor-bearing mice model [26], suggesting the expression level of heme in brain tumors might not effectively abrogate the anticancer effect of DMC. These results suggest that the anticancer efficacy of DMC in various cancers in vivo might be dependent on the different proportions of heme-derived free iron and DMC in tumor tissues.…”

“…Due to the low oral bioavailability, the clinical use of CUR in cancer therapy is limited. Recently, accumulating evidence proved that the second most abundant active component of curcuminoids, DMC, is an more efficient and stable agent than CUR for cancer therapy [24][25][26]. Until now, the precise cellular mechanisms of DMC against OSCCs have not yet been fully clarified.…”