Inhibition of cancer antioxidant defense by natural compounds

Abstract

All classic, non-surgical anticancer approaches like chemotherapy, radiotherapy or photodynamic therapy kill cancer cells by inducing severe oxidative stress. Even tough chemo- and radiotherapy are still a gold standard in cancer treatment, the identification of non-toxic compounds that enhance their selectivity, would allow for lowering their doses, reduce side effects and risk of second cancers. Many natural products have the ability to sensitize cancer cells to oxidative stress induced by chemo- and radiotherapy by limiting antioxidant capacity of cancer cells. Blocking antioxidant defense in tumors decreases their ability to balance oxidative insult and results in cell death. Though one should bear in mind that the same natural compound often exerts both anti-oxidant and pro-oxidant properties, depending on concentration used, cell type, exposure time and environmental conditions. Here we present a comprehensive overview of natural products that inhibit major antioxidant defense mechanisms in cancer cells and discuss their potential in clinical application.

Antioxidants as a Double-Edged Sword in the Treatment of Cancer

“…Against, cancer cells boost their anti-apoptotic mechanisms like a nuclear factor kappa-light-chain-enhancer of activated B cell (NFĸB) pathway to escape cell death [9]. Disruption of redox balance in cells causes activation of the transcription factors like nuclear factor erythroid 2-related factor 2 (Nrf2), NFĸB, and activator protein 1 (AP-1) as redox-sensitive transcription factors [28]. Nrf2 transcription factor is the major driver of antioxidant expression that leads to protection against DNA damage, endogenous and exogenous hazards, and consequent cancer initiation [29,30].…”

Prospect of natural products in glioma: A novel avenue in glioma management

“…Curcumin, a well‐known constituent of turmeric, is being evaluated for its effectiveness against several cancers including brain cancer, breast cancer, lung cancer, and prostate cancer (Ravindran, Prasad, & Aggarwal, ). Several polyphenols have shown potent anticancer effect because of their antioxidant property (Banerjee & Mandal, ; Sznarkowska et al, ). Overall, natural compounds have superior efficacy and more importantly lesser toxicity when compared with synthetic chemotherapeutic agents (Sak, ; Yuan, Ma, Ye, & Piao, ).…”

“…Researchers also explored microbes and the marine organism as a source of natural compounds (Discovery, ). Nature‐derived compounds have various pharmacological activities including antiangiogenic (Sulaiman, Basavarajappa, & Corson, ), antiprotozoal (Jones, Grkovic, Sykes, & Avery, ; Singh, Mishra, Bajpai, Singh, & Tiwari, ), antiatherosclerotic (Orekhov, Sobenin, Revin, & Bobryshev, ), antimicrobial (Farha & Brown, ; Genilloud, ), anti‐obesity (Fu, Jiang, Guo, & Su, ), antioxidant (Fiedor & Burda, ), antidiabetic (Nazaruk & Borzym‐Kluczyk, ), hepatoprotective (Madrigal‐Santillán, ), anti‐inflammatory (Arulselvan et al, ), neuroprotective (Ebrahimi & Schluesener, ; Essa et al, ), and chemotherapeutic (Amin et al, ; Sznarkowska, Kostecka, Meller, & Bielawski, ; Yang et al, ) effects.…”

Advancing the Role of Gamma-Tocotrienol as Proteasomes Inhibitor: A Quantitative Proteomic Analysis of MDA-MB-231 Human Breast Cancer Cells

“…Studies have shown that tocotrienols were able to induce apoptosis in malignant cells, but not in non-malignant cells [8,9]. This selectivity could be largely due to the reduced antioxidant defense expressed by these malignant cells when compared to non-malignant cells [10] or might involve many other unknown factors. The selectivity of T3 for cancer cells might be dependent on the ability of the former to specifically target and downregulate proteins, which are abnormally upregulated in carcinogenic but not in normal cells.…”