Therapeutic Potential of the Natural Compound S-Adenosylmethionine as a Chemoprotective Synergistic Agent in Breast, and Head and Neck Cancer Treatment: Current Status of Research

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Abstract

The present review summarizes the most recent studies focusing on the synergistic antitumor effect of the physiological methyl donor S-adenosylmethionine (AdoMet) in association with the main drugs used against breast cancer and head and neck squamous cell carcinoma (HNSCC), two highly aggressive and metastatic malignancies. In these two tumors the chemotherapy approach is recommended as the first choice despite the numerous side effects and recurrence of metastasis, so better tolerated treatments are needed to overcome this problem. In this regard, combination therapy with natural compounds, such as AdoMet, a molecule with pleiotropic effects on multiple cellular processes, is emerging as a suitable strategy to achieve synergistic anticancer efficacy. In this context, the analysis of studies conducted in the literature highlighted AdoMet as one of the most effective and promising chemosensitizing agents to be taken into consideration for inclusion in emerging antitumor therapeutic modalities such as nanotechnologies.

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Cancer statistics, 2020

Rebecca Siegel, Kimberly D Miller, Ahmedin Jemal (2020)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2016) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2017) were collected by the National Center for Health Statistics. In 2020, 1,806,590 new cancer cases and 606,520 cancer deaths are projected to occur in the United States. The cancer death rate rose until 1991, then fell continuously through 2017, resulting in an overall decline of 29% that translates into an estimated 2.9 million fewer cancer deaths than would have occurred if peak rates had persisted. This progress is driven by long-term declines in death rates for the 4 leading cancers (lung, colorectal, breast, prostate); however, over the past decade (2008-2017), reductions slowed for female breast and colorectal cancers, and halted for prostate cancer. In contrast, declines accelerated for lung cancer, from 3% annually during 2008 through 2013 to 5% during 2013 through 2017 in men and from 2% to almost 4% in women, spurring the largest ever single-year drop in overall cancer mortality of 2.2% from 2016 to 2017. Yet lung cancer still caused more deaths in 2017 than breast, prostate, colorectal, and brain cancers combined. Recent mortality declines were also dramatic for melanoma of the skin in the wake of US Food and Drug Administration approval of new therapies for metastatic disease, escalating to 7% annually during 2013 through 2017 from 1% during 2006 through 2010 in men and women aged 50 to 64 years and from 2% to 3% in those aged 20 to 49 years; annual declines of 5% to 6% in individuals aged 65 years and older are particularly striking because rates in this age group were increasing prior to 2013. It is also notable that long-term rapid increases in liver cancer mortality have attenuated in women and stabilized in men. In summary, slowing momentum for some cancers amenable to early detection is juxtaposed with notable gains for other common cancers.

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Cisplatin in cancer therapy: molecular mechanisms of action.

Shaloam R Dasari, Paul Bernard Tchounwou (2014)

Cisplatin, cisplatinum, or cis-diamminedichloroplatinum (II), is a well-known chemotherapeutic drug. It has been used for treatment of numerous human cancers including bladder, head and neck, lung, ovarian, and testicular cancers. It is effective against various types of cancers, including carcinomas, germ cell tumors, lymphomas, and sarcomas. Its mode of action has been linked to its ability to crosslink with the purine bases on the DNA; interfering with DNA repair mechanisms, causing DNA damage, and subsequently inducing apoptosis in cancer cells. However, because of drug resistance and numerous undesirable side effects such as severe kidney problems, allergic reactions, decrease immunity to infections, gastrointestinal disorders, hemorrhage, and hearing loss especially in younger patients, other platinum-containing anti-cancer drugs such as carboplatin, oxaliplatin and others, have also been used. Furthermore, combination therapies of cisplatin with other drugs have been highly considered to overcome drug-resistance and reduce toxicity. This comprehensive review highlights the physicochemical properties of cisplatin and related platinum-based drugs, and discusses its uses (either alone or in combination with other drugs) for the treatment of various human cancers. A special attention is paid to its molecular mechanisms of action, and its undesirable side effects. Copyright © 2014 Elsevier B.V. All rights reserved.

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Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems.

Oktay Tacar, Pornsak Sriamornsak, Crispin R Dass (2013)

The frontline drug doxorubicin has been used for treating cancer for over 30 years. While providing a cure in select cases, doxorubicin causes toxicity to most major organs, especially life-threatening cardiotoxicity, which forces the treatment to become dose-limiting. Doxorubicin is known to bind to DNA-associated enzymes, intercalate with DNA base pairs, and target multiple molecular targets to produce a range of cytotoxic effects. For instance, it causes the activation of various molecular signals from AMPK (AMP-activated protein kinase inducing apoptosis) to influence the Bcl-2/Bax apoptosis pathway. By altering the Bcl-2/Bax ratio, downstream activation of different caspases can occur resulting in apoptosis. Doxorubicin also induces apoptosis and necrosis in healthy tissue causing toxicity in the brain, liver, kidney and heart. Over the years, many studies have been conducted to devise a drug delivery system that would eliminate these adverse affects including liposomes, hydrogel and nanoparticulate systems, and we highlight the pros and cons of these drug delivery systems. Overall the future for the continued use of doxorubicin clinically against cancer looks set to be prolonged, provided certain enhancements as listed above are made to its chemistry, delivery and toxicity. Increased efficacy depends on these three aims being met satisfactorily as discussed in turn in this review. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

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Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 13 November 2020

Publication date Collection: November 2020

Volume: 21

Issue: 22

Electronic Location Identifier: 8547

Article

Publisher ID: ijms-21-08547

DOI: 10.3390/ijms21228547

PMC ID: 7697526

PubMed ID: 33202711

SO-VID: f50e341c-e1dc-4a0a-bd13-5463b421013b

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Therapeutic Potential of the Natural Compound S-Adenosylmethionine as a Chemoprotective Synergistic Agent in Breast, and Head and Neck Cancer Treatment: Current Status of Research

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Most cited references 101

Cancer statistics, 2020

Cisplatin in cancer therapy: molecular mechanisms of action.

Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems.

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