Розмарин и рак Rosmarinus officinalis & cancer Научные исследования
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1. IntroductionNatural compounds have been used extensively in the treatment of many diseases and are of interest to researchers both in their natural forms and as templates for synthetic modification. Natural compounds currently used in medicine exhibit a very wide chemical diversity, and together with their analogues and several other natural products, they demonstrate the importance of compounds from natural sources in modern drug discovery efforts. Sample sources and molecular mechanisms are highly important in the development of novel, clinically useful anticancer agents [1]. Interest in natural compounds has grown in recent years because of concerns about drug costs and safety. For example, glioblastoma kills almost everyone who gets it, usually in a little over a year. In effect, the $1.3 billion spent by a pharmaceutical company on a new glioblastoma drug discovery had the limited impact of improving patients’ lives for about one year. This illustrates the need for new sources for drug discovery, and natural sources provide valuable information for research in this area. During the past decade, tremendous progress has been made toward understanding the cellular and molecular mechanisms underlying the process of carcinogenesis, leading to the development of potential cancer prevention options termed chemoprevention [2]. The goal of chemoprevention is to use noncytotoxic natural agents to inhibit or reverse the development and progression of precancerous cells [3]. Cancer is a complicated disease that may develop in humans over a number of years (Figure 1). Development of a tumor starts with a normal cell that is transformed through the activation of proto-oncogenes and the suppression of tumor suppressor genes such as p53. The transformed cell no longer behaves like a normal cell but begins to exhibit the properties of a cancer cell. Such transformation in the cells makes them self-sufficient in growth signals and resistant to antigrowth signals, resulting in uncontainable proliferation. In addition, these cells are able to avoid apoptosis, resulting in tumor growth. This whole process of transformation may take 10–20 years. The growth of the tumor is aided by angiogenesis, which not only provides nutrition to the tumor but also enables its invasion to surrounding tissues, and its metastasis to distant tissues; the latter is usually lethal. Roles of the NF-κB-mediated inflammatory pathway in cellular transformation and in cancer cell survival, proliferation, invasion, angiogenesis, and metastasis. Inflammation, which occurs as a response to cancer, has two stages, acute and chronic. Acute inflammation, the initial stage of inflammation, represents innate immunity; it is mediated through the activation of the immune system, lasts for a short period and generally is regarded as therapeutic inflammation. If the inflammation persists for a long period of time, however, the second stage, chronic inflammation, sets in [4]. Chronic inflammation has been linked with most chronic illnesses, including cancer, cardiovascular disease, diabetes, obesity, pulmonary disease, and neurologic disease [5], the current review focuses on the role of triterpenoids in targeting inflammatory pathways for prevention and treatment of cancer. Evidence from tissue culture, animal, and clinical studies suggests that more than 20,000 triterpenoid-rich fruits are found in nature and have the potential ability to limit the development and severity of certain cancers and inflammatory diseases [6]. These triterpenoids, along with their close chemical relatives the steroids, are members of a larger family of related structures called cyclosqualenoids. Triterpenoids, synthesized in many plants by the cyclization of squalene [7], are widely used in Asian medicine. More than 100 prescribed drugs in the United States are obtained from natural sources and represent one fourth of the total drugs used. Apart from these drugs that originate from natural sources, other phytochemicals also serve as potential drugs after structural modification [8]. Scientific studies have shown triterpenoids to be potential anti-inflammatory and anticancer agents. This review covers the anti-inflammatory and anticancer property of triterpenoids originating from plants such as onion, ginseng, brahmi, azuma ichirinsou, shallaki, salai guggal, lei gong teng, licorice, mango, olive, bearberry, Chinese bellflower, sickle-leaf, tulsi, ashwagandha, and others (Figure 2 and Table 1) that target one or more of the various phases of tumorigenesis. As more than 20,000 triterpenoids are available in nature and it is difficult to describe them all, this review summarizes what we know of a few triterpenoids with structural similarity, including avicin, erythrodiol, madecassic acid, maslinic acid, momordin, saikosaponins, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) and its methyl ester CDDO-Me, platycodon D, withanolide, diosgenin, betulinic acid, boswellic acids, pristimerin, and celastrol (Figure 3); their active moieties for anti-inflammatory and anticancer activity Table 1Common medicinally active triterpenoid obtained from plants.
The review also focuses on targets for inflammation, proliferation, apoptosis, invasion, metastasis and angiogenesis. Because a large portion of these nutraceuticals show great potential for targeting cancer through various mechanisms—such as the downregulation of transcription factors (e.g., nuclear factor-kappaB [NF-κB]), anti-apoptotic proteins (e.g., bcl-2, bcl-xL), promoters of cell proliferation (e.g., cyclooxygenase-2 [COX-2], cyclin D1, c-myc), invasive and metastatic genes (e.g., matrix metalloproteinases [MMPs], intracellular adhesion molecule-1 (ICAM-1), and angiogenic protein (vascular endothelial growth factor (VEGF)) (Table 2); and other uses of these triterpenoids are shown in Table 3. This review summarizes the sources and structures of triterpenoids and provides insight into the underlying molecular targets for cancer prevention and therapy. Table 3Other uses of triterpenoid in treatment of chronic diseases.
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