Curcumin―The Paradigm of a Multi-Target Natural Compound with Applications in Cancer Prevention and Treatment

Abstract

As cancer is a multifactor disease, it may require treatment with compounds able to target multiple intracellular components. We summarize here how curcumin is able to modulate many components of intracellular signaling pathways implicated in inflammation, cell proliferation and invasion and to induce genetic modulations eventually leading to tumor cell death. Clinical applications of this natural compound were initially limited by its low solubility and bioavailability in both plasma and tissues but combination with adjuvant and delivery vehicles was reported to largely improve bio-availability of curcumin. Moreover, curcumin was reported to act in synergism with several natural compounds or synthetic agents commonly used in chemotherapy. Based on this, curcumin could thus be considered as a good candidate for cancer prevention and treatment when used alone or in combination with other conventional treatments.

The Acetylenic Tricyclic Bis(cyano enone), TBE-31 Inhibits Non–Small Cell Lung Cancer Cell Migration through Direct Binding with Actin

“…The enormous biologic diversity of cancer has led to limited promise for therapies that target single signaling molecules. It has been suggested that strategic combinations of agents targeting against the most critical alterations in cancer will be needed, or simply the use of more unspecific agents that modulate several relevant targets simultaneously (46,47). Not surprisingly, drug discovery has moved toward investigating multitarget drugs in the last decade, in a large part due to the development of cancer therapeutics (48)(49)(50).…”

Carboplatin resistant human laryngeal carcinoma cells are cross resistant to curcumin due to reduced curcumin accumulation

“…Curcumin could be an excellent candidate to target a multifactorial disease like cancer because of its broad range of activities, based on its ability to affect multiple intracellular targets (Kunnumakkara et al, 2008;Lopez-Lazaro, 2008;Teiten et al, 2010).…”

“…Although curcumin has shown a wide range of beneficial pharmacological effects, its anticancer properties have attracted a great interest. It has been shown that curcumin can induce the death of cancer cells and inhibit the formation of tumors in animal models of carcinogenesis (Kunnumakkara et al, 2008;Lopez-Lazaro, 2008;Teiten et al, 2010). Since curcumin influences multiple components of intracellular signaling pathways and molecular targets involved in the development and progression of cancer (Lopez-Lazaro, 2008;Teiten et al, 2010), it is a promising drug for the treatment of cancer as a multifactorial disease.…”

“…It has been shown that curcumin can induce the death of cancer cells and inhibit the formation of tumors in animal models of carcinogenesis (Kunnumakkara et al, 2008;Lopez-Lazaro, 2008;Teiten et al, 2010). Since curcumin influences multiple components of intracellular signaling pathways and molecular targets involved in the development and progression of cancer (Lopez-Lazaro, 2008;Teiten et al, 2010), it is a promising drug for the treatment of cancer as a multifactorial disease. The ongoing clinical trials should determine the possible beneficial effect of curcumin in cancer treatment, when given alone or in combination with conventional anticancer drugs (Teiten et al, 2010).…”

Potential Herbal Therapy of HMGB1-Targeting Agent in Sepsis

“…(3) Herbal compounds could enter cells and interact with proinflammatory intracellular kinases or signaling pathways such as NF-κB, c-Jun N-terminal kinases (JNK1/2) or signal transducer and activator of transcription 3 (STAT3) and inflammatory intracellular molecules such as interleukin-6 (IL-6), IL-8, monocyte chemoattractant protein 1 (MCP-1), TNF-α, IL-1β or atrogin-1. For example, curcumin (from Curcuma longa), inhibited inflammatory signaling pathways such as NF-κB pathway, STAT and COX-2 signaling and it inhibited cell proliferation pathways such as phosphoinositide 3-kinase, protein kinase B and mammalian target of rapamycin [23]. Therefore, the potential molecular mechanisms for barrier protective effects against HMGB1 signaling might be mediated by inhibiting the interaction of HMGB1 to its receptors, inhibiting the inflammatory signaling pathway of HMGB1 or nuclear signaling pathways of HMGB1.…”