Molecular Mechanisms of Anti-metastatic Activity of Curcumin

Abstract

Abstract. Cancer is the leading cause of death worldwide. Although cancer occurs as a localized disease, its morbidity and mortality rates remain high due to the ability of cancer cells to break-off from the primary tumor and spread to distant organs. Currently, chemotherapy is the main treatment for cancer; however, the increase in proportion of drug-resistant cancer cells and unpleasant side-effects of chemotherapy are still the major challenges in cancer therapy. Curcumin is a natural polyphenol compound and the main bioactive constituent of Indian spice turmeric, widely used in Indian and Chinese medicines. Curcumin has well-known therapeutic actions, including antiinflammatory, anti-microbial, anti-oxidant and anti-cancer properties. Curcumin induces cancer cell apoptosis through regulating various signaling pathways and arresting tumor cell cycle. Curcumin's therapeutic/ preventative actions on metastatic cancers have not been yet fully understood and studied. The present review explores the potential anti-metastatic mechanisms of curcumin, including inhibition of transcription factors and their signaling pathways (e.g., inflammatory cytokines (e.g., CXCL1, CXCL2, multiple proteases (e.g., uPA, MMPs), multiple protein kinases (e.g., MAPKs, FAK), regulation of miRNAs (e.g., miR21, miR181b) and heat shock proteins (HLJ1). In addition, possible synergistic actions of combination therapy of curcumin with current chemotherapies are discussed in this review.Despite all recent advances in oncology, cancer is still one of the deadliest diseases around the world (1). Cancer occurs as a localized disease but can spread to distant organs through migration, invasion and metastasis (2). Metastatic cancer is one of the major causes of death in cancer patients. Metastasis is a complex process involving multiple steps: (i) local migration through degrading basement membrane and extracellular matrix (ECM), (ii) intravasation into blood and/or lymphatic vessels, (iii) circulating to the target organ site, (iv) extravasation into target organ tissue and, finally, (v) multiplication in the target organ (2, 3). These steps are mediated by various factors, including growth factors, proteolysis degradation of extracellular matrix, cell-cell adhesion, cytoskeleton remodeling and changes of genes' expressions (2, 3). Metastasis is a non-random process that means each metastatic cancer type has its own preferred site of metastasis. For example, breast cancer cells preferentially metastasize to regional lymph nodes, liver, lungs and bone (4). Nowadays, there are different therapeutic approaches available for patients with metastatic cancers, including surgery, radiotherapy and chemotherapy. Chemotherapy remains the main treatment modality for cancer patients because of its ability of preventing invasion and metastasis. However, the morbidity and mortality rates in patients with metastatic cancer still remain high since current chemotherapy agents fail to selectively and effectively kill cancer cells without destroying normal ce...

Curcuminoids Lower Plasma Leptin Concentrations: A Meta‐analysis

“…Curcumin is the main bioactive constituent of turmeric that has a long history of use both as a dietary spice and as a traditional medicine. Curcumin has antiinflammatory, anti-microbial, anti-oxidant, and anticancer properties (Deng et al, 2016;Perez-Perez et al, 2017). These actions appear to be due to the regulation of the expression of inflammatory cytokines, growth factors, adhesion molecules, and cell cycle proteins (Deng et al, 2016).…”

“…Curcumin (diferuloylmethane) is a naturally occurring polyphenol that is derived from turmeric (Curcuma longa L.) and a common ingredient in Eastern cuisine. Investigative clinical trials have suggested that curcumin has antioxidant (Panahi et al, 2016a;Sahebkar et al, 2015b), antiinflammatory (Panahi et al, 2012;Sahebkar, 2014a), and immunomodulatory (Ghandadi and Sahebkar, 2017;Karimian et al, 2017;Ganjali et al, 2014) properties and is effective in a wide number of diverse conditions including osteoarthritis and rheumatoid arthritis (Kurien et al, 2015;Panahi et al, 2014c;Sahebkar and Henrotin, 2016), metabolic syndrome (Inzaugarat et al, 2017;Panahi et al, 2015b;Panahi et al, 2014b;Sahebkar, 2013;Rahmani et al, 2016), cancer (Deng et al, 2016;Teymouri et al, 2017;Mirzaei et al, 2016;Momtazi et al, 2016), dyslipidemia (Panahi et al, 2016c;Sahebkar, 2014b;Ganjali et al, 2017), chronic obstructive pulmonary disease (Lelli et al, 2017;Panahi et al, 2014a), and anxiety and depression (Esmaily et al, 2015;Panahi et al, 2015a). Curcumin has a direct effect on adipokine release from adipocytes (Panahi et al, 2016b;Hajavi et al, 2017) with the suggestion that it may induce lipolysis and regulate leptin in animals (Song and Choi, 2016).…”

Turmeric (Curcuma longa) and its major constituent (curcumin) as nontoxic and safe substances: Review

“…It has preventive effects on tobacco smoke‐induced liver cancer (Liang et al, ). Recently, this agent has shown antimetastatic effect (de Campos et al, ; Deng, Verron, & Rohanizadeh, ). Curcumin also has cytotoxic effects on tumor cells (Khosropanah et al, ; Liu & Chen, ; Syng‐Ai, Kumari, & Khar, ).…”

An intratumoral injectable, electrostatic, cross-linkable curcumin depot and synergistic enhancement of anticancer activity

“…Cur degrades quickly at normal physiological condition. [14][15][16][31][32][33] In this work, the amount of Cur remaining in the tumor after intratumoral injection of the free Cur was only 5% at 1 day in tumor. This result was in accordance to previous reports where it has been observed that Cur decomposed above 90% within 1 day at physiological condition.…”

“…13 Although Cur has shown efficacy against numerous cancers, its therapeutic potential has been limited by poor bioavailability due to poor absorption, rapid metabolism and rapid systemic elimination. [14][15][16] Therefore, research has been focused on improving the limitations and drawbacks of the conventional delivery of Cur.…”