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.

Curcumin (diferuloylmethane), an orange‑yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of Curcuma longa. For centuries, curcumin has been used in medicinal preparations and as a food colorant. In recent years, extensive in vitro and in vivo studies have suggested that curcumin possesses activity against cancer, viral infection, arthritis, amyloid aggregation, oxidation and inflammation. Curcumin exerts anticancer effects primarily by activating apoptotic pathways in cancer cells and inhibiting pro‑cancer processes, including inflammation, angiogenesis and metastasis. Curcumin targets numerous signaling pathways associated with cancer therapy, including pathways mediated by p53, Ras, phosphatidylinositol‑3‑kinase, protein kinase B, Wnt‑β catenin and mammalian target of rapamycin. Clinical studies have demonstrated that curcumin alone or combined with other drugs exhibits promising anticancer activity in patients with breast cancer without adverse effects. In the present review, the chemistry and bioavailability of curcumin and its molecular targets in breast cancer are discussed. Future research directions are discussed to further understand this promising natural product.

/pdf/molecular-targets-of-curcumin-in-breast-cancer-review-2mi3pnkqgn.pdf

Molecular targets of curcumin in breast cancer (Review).

Current scenario of indole derivatives with potential anti-drug-resistant cancer activity.

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

Induction of programmed necrosis: A novel anti-cancer strategy for natural compounds.

Dihydronortanshinone, a natural product, alleviates LPS-induced inflammatory response through NF-κB, mitochondrial ROS, and MAPK pathways

Aims: Most chemotherapeutic agents exploit apoptotic signaling to trigger cancer cell death, which frequently results in drug resistance. Necroptosis, a nonapoptotic form of regulated cell death, offers an alternative strategy to eradicate apoptosis-resistant cancer cells. We previously reported a natural necroptosis inducer 2-methoxy-6-acetyl-7-methyljuglone (MAM) in A549 lung cancer cells. The current study is designed to investigate the detailed necroptotic signaling and its cytotoxicity on drug-resistant cancer cells. Furthermore, in vivo anticancer effects were also evaluated in nude mice model. Results: MAM directly targets receptor-interacting protein 1 (RIP1) kinase in A549 and H1299 cells, which is responsible for reactive oxygen species (ROS, mainly hydrogen peroxide) generation. A positive feedback loop between calcium (Ca2+) and c-Jun N-terminal kinase (JNK) occurred following ROS generation, leading to lysosomal membrane permeabilization and mitochondrial dysfunction. MAM showed similar cytotoxic potency toward cisplatin-resistant A549 (A549/Cis) cells by inducing necroptosis as confirmed by the protective effect of 7-Cl-O-Nec-1 (Nec-1s) and by the morphological characteristics obtained via transmission electron microscopy. Interestingly, tumor necrosis factor alpha (TNFα) was not involved in this process. Intraperitoneal injection of MAM significantly suppressed tumor growth in A549 tumor xenograft without significant body weight loss and multiorgan toxicities. Innovation and Conclusion: Our findings demonstrate that MAM induces necroptosis in A549 and H1299 lung cancer cells by targeting RIP1 kinase and ROS in a TNFα-independent manner. MAM kills A549/Cis cells with similar potency through induction of necroptosis. MAM shows anticancer effect in animal model. The present study raises the therapeutic possibility and strategy to combat cancer by the induction of necroptosis.

Ying Hou

Papers

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

Induction of programmed necrosis: A novel anti-cancer strategy for natural compounds.

Dihydronortanshinone, a natural product, alleviates LPS-induced inflammatory response through NF-κB, mitochondrial ROS, and MAPK pathways

Inhibition of Lung Cancer by 2-Methoxy-6-Acetyl-7-Methyljuglone Through Induction of Necroptosis by Targeting Receptor-Interacting Protein 1

Induction of an MLKL mediated non-canonical necroptosis through reactive oxygen species by tanshinol A in lung cancer cells.