Traditional chemotherapy is being considered due to hindrances caused by systemic toxicity. Currently, the administration of multiple chemotherapeutic drugs with different biochemical/molecular targets, known as combination chemotherapy, has attained numerous benefits like efficacy enhancement and amelioration of adverse effects that has been broadly applied to various cancer types. Additionally, seeking natural-based alternatives with less toxicity has become more important. Experimental evidence suggests that herbal extracts such as Solanum nigrum and Claviceps purpurea and isolated herbal compounds (e.g., curcumin, resveratrol, and matairesinol) combined with antitumoral drugs have the potential to attenuate resistance against cancer therapy and to exert chemoprotective actions. Plant products are not free of risks: Herb adverse effects, including herb-drug interactions, should be carefully considered. LINKED ARTICLES: This article is part of a themed section on The Pharmacology of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.6/issuetoc.

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bph.14816

Natural compounds as potential adjuvants to cancer therapy: preclinical evidence

Erastin was initially discovered as a small molecule compound that selectively kills tumor cells expressing ST and RASV12 and was later widely investigated as an inducer of ferroptosis. Ferroptosis is a recently discovered form of cell death caused by peroxidation induced by the accumulation of intracellular lipid reactive oxygen species (L-ROS) in an iron-dependent manner. Erastin can mediate ferroptosis through a variety of molecules including the cystine-glutamate transport receptor (system XC -), the voltage-dependent anion channel (VDAC), and p53. Erastin is able to enhance the sensitivity of chemotherapy and radiotherapy, suggesting a promising future in cancer therapy. We hope that this review will help to better understand the role of erastin in ferroptosis and lay the foundation for further research and the development of erastin-based cancer therapies in the future.

/pdf/the-role-of-erastin-in-ferroptosis-and-its-prospects-in-gkok2ikatg.pdf

The Role of Erastin in Ferroptosis and Its Prospects in Cancer Therapy.

Efforts to control costs and improve quality are working. Now Congress will determine how best to control future health care costs and extend care to the nation's uninsured.

Progress and promise.

Cytosolic calcium mediates RIP1/RIP3 complex-dependent necroptosis through JNK activation and mitochondrial ROS production in human colon cancer cells.

Cucurbit[7]uril (CB[7]), belonging to the cucurbit[n]uril family (CB[n], n = 5-8, 10, or 13-15), may form host-guest complexes with a variety of small molecules of biomedical interest. The physical and chemical properties of the complexed drugs are often improved as a result of this complexation, suggesting the potential application of CB[7] as a pharmaceutical excipient. This review has summarized the most recent research progress reported between 2011 and early 2017 regarding the biocompatibility of CB[7] and the influence of CB[7] on the stability, solubility, biouptake, and biological activities (including therapeutic efficacies and toxicities) of guest drug molecules. Through this systemic summary and analysis, we intend to stimulate further research efforts in this area and promote the use of CB[7] as an emerging pharmaceutical excipient to improve various properties of drug molecules (or active pharmaceutical ingredients).

Cucurbit[7]uril: an emerging candidate for pharmaceutical excipients

Chemotherapy is the standard internal medical treatment for cancer. However, the resistance of cancer cells to nearly all kinds of chemotherapeutic drugs and targeted drugs has become prevalent, and approximately 80-90% of deaths in cancer patients are directly or indirectly attributed to drug resistance. The progress of new drug research and development has also been impeded by the occurrence of drug resistance, which has emerged as a considerable challenge in cancer therapy. Fortunately, natural products with diverse chemical structures and pharmacological effects serve as effective substances against drug resistance. Since the discovery of a series of drug-resistant proteins, drug-efflux inhibition has been applied as the primary strategy to overcome drug resistance by maintaining the intracellular concentrations of chemotherapeutic drugs. Nonapoptotic cell death is considered an alternative strategy because most cases of drug resistance result in evasion and insensitivity to apoptosis. In this concise review, we summarize two strategies using natural products against drug resistance.

Natural products to prevent drug resistance in cancer chemotherapy: a review

Psoralidin induced reactive oxygen species (ROS)-dependent DNA damage and protective autophagy mediated by NOX4 in breast cancer cells.

Camptothecin (CPT), a natural antineoplastic agent that was originally isolated from the bark and stem of Camptotheca acuminata, targets a wide range of cancers by inhibition of topoisomerase I during DNA replication. In this study, we investigated the use of cucurbit[7]uril (CB[7]) for molecular encapsulation of CPT and the associated benefits of such encapsulation of CPT on its anti-cancer activity, and side effects have been systemically evaluated both in vitro and in vivo. The cytotoxicity of the free CPT and complexed CPT (CPT@CB[7]) was examined by MTT assay using both a healthy liver cell line (L02) and a liver cancer cell line (Bel-7402). Interestingly, both the free CPT and CPT@CB[7] demonstrated comparable anti-cancer efficacy in vitro on the cancer cell line Bel-7402, whereas CPT@CB[7] showed obviously lower toxicity on the healthy liver cell line L02, in comparison with the free CPT. The anti-cancer/anti-angiogenic activity and non-specific toxicity of both free CPT and CPT@CB[7] were further investigated in vivo with both transgenic and wild-type zebrafish models, showing again that CPT@CB[7] exhibited reduced non-specific toxicities with well-preserved anti-angiogenic activities, when compared with the free CPT. These results demonstrate that CB[7] may work as a functional excipient for alleviation of undesired side-effects of selected organic drugs.

/pdf/influence-of-supramolecular-encapsulation-of-camptothecin-by-5exw1gk7og.pdf

Influence of supramolecular encapsulation of camptothecin by cucurbit[7]uril: reduced toxicity and preserved anti-cancer activity

Cucurbitacin B (Cuc B), a natural product, induced both protective autophagy and DNA damage mediated by ROS while the detailed mechanisms remain unclear. This study explored the mechanism of Cuc B-induced DNA damage and autophagy. Cuc B decreased cell viability in concentration- and time-dependent manners. Cuc B caused long comet tails and increased expression of γ-H2AX, phosphorylation of ATM/ATR, and Chk1/Chk2. Cuc B induced autophagy as evidenced by monodansylcadaverine (MDC) staining, increased expression of LC3II, phosphorylated ULK1, and decreased expression of phosphorylated AKT, mTOR. Cuc B induced apoptosis mediated by Bcl-2 family proteins and caspase activation. Furthermore, Cuc B induced ROS formation, which was inhibited by N-acetyl-L-cysteine (NAC). NAC pretreatment dramatically reversed Cuc B-induced DNA damage, autophagy, and apoptosis. Cuc B-induced apoptosis was reversed by NAC but enhanced by 3-methyladenine (3-MA), chloroquine (CQ), and silencing phosphatase and tensin homolog (PTEN). 3-MA and CQ showed no effect on Cuc B-induced DNA damage. In addition, Cuc B increased PTEN phosphorylation and silence PTEN restored Cuc B-induced autophagic protein expressions without affecting DNA damage. In summary, Cuc B induced DNA damage, apoptosis, and protective autophagy mediated by ROS. PTEN activation in response to DNA damage bridged DNA damage and prosurvival autophagy.

https://downloads.hindawi.com/journals/omcl/2016/4313204.pdf

Yanan Niu

Papers

Natural products to prevent drug resistance in cancer chemotherapy: a review

Psoralidin induced reactive oxygen species (ROS)-dependent DNA damage and protective autophagy mediated by NOX4 in breast cancer cells.

Influence of supramolecular encapsulation of camptothecin by cucurbit[7]uril: reduced toxicity and preserved anti-cancer activity

PTEN Activation by DNA Damage Induces Protective Autophagy in Response to Cucurbitacin B in Hepatocellular Carcinoma Cells.

Alleviation of Hepatotoxicity of Arecoline (Areca Alkaloid) by a Synthetic Receptor