Abstract
Cisplatin and other platinum-based drugs, such as carboplatin, ormaplatin, and oxaliplatin, have been widely used to treat a multitude of human cancers. However, a considerable proportion of patients often relapse due to drug resistance and/or toxicity to multiple organs including the liver, kidneys, gastrointestinal tract, and the cardiovascular, hematologic, and nervous systems. In this study, we sought to provide a comprehensive review of the current state of the science highlighting the use of cisplatin in cancer therapy, with a special emphasis on its molecular mechanisms of action, and treatment modalities including the combination therapy with natural products. Hence, we searched the literature using various scientific databases., such as MEDLINE, PubMed, Google Scholar, and relevant sources, to collect and review relevant publications on cisplatin, natural products, combination therapy, uses in cancer treatment, modes of action, and therapeutic strategies. Our search results revealed that new strategic approaches for cancer treatment, including the combination therapy of cisplatin and natural products, have been evaluated with some degree of success. Scientific evidence from both in vitro and in vivo studies demonstrates that many medicinal plants contain bioactive compounds that are promising candidates for the treatment of human diseases, and therefore represent an excellent source for drug discovery. In preclinical studies, it has been demonstrated that natural products not only enhance the therapeutic activity of cisplatin but also attenuate its chemotherapy-induced toxicity. Many experimental studies have also reported that natural products exert their therapeutic action by triggering apoptosis through modulation of mitogen-activated protein kinase (MAPK) and p53 signal transduction pathways and enhancement of cisplatin chemosensitivity. Furthermore, natural products protect against cisplatin-induced organ toxicity by modulating several gene transcription factors and inducing cell death through apoptosis and/or necrosis. In addition, formulations of cisplatin with polymeric, lipid, inorganic, and carbon-based nano-drug delivery systems have been found to delay drug release, prolong half-life, and reduce systemic toxicity while other formulations, such as nanocapsules, nanogels, and hydrogels, have been reported to enhance cell penetration, target cancer cells, and inhibit tumor progression.
Highlights
In 2020, the burden of cancer in the U.S was estimated to be 1.8 million new diagnosed cases of cancer, among which 43% accounted for prostate, lung, and colorectal cancer in men and 50% accounted for breast, lung, and colorectal cancer in women
We demonstrated in our research laboratory that Vernonia amygdalina inhibited the proliferation of breast cancer (MCF-7) cells [139], Vernonia amygdalina Delile inhibited the growth of prostate cancer (PC-3) cells [128], and Vernonia calvonia caused growth arrest of ovarian cancer (OVCAR-3) cells [127]
Its mode of action involves covalent binding to deoxyribonucleic acid (DNA), forming adducts and thereby triggering apoptosis and/or necrosis through a series of biochemical mechanisms that involve oxidative stress, DNA damage, and interference in various signal transduction pathways
Summary
In 2020, the burden of cancer in the U.S was estimated to be 1.8 million new diagnosed cases of cancer, among which 43% accounted for prostate, lung, and colorectal cancer in men and 50% accounted for breast, lung, and colorectal cancer in women. Research has shown that certain risk factors are associated with the development of cancer, causing substantial morbidity and mortality rates. After the Second World War, Sydney Farber administered antifolates to children with acute lymphoblastic leukemia to suppress proliferation of malignant cells and restore normal bone marrow function. He observed that blocking the function of folate-requiring enzymes successfully induced remission. George Hitchings and Gertrude Elion developed 6-mercaptopurine as an anticancer agent, which inhibits ribonucleic acid (RNA) and DNA synthesis [9] This is a summary of the humble beginnings of modern chemotherapy. Sci. 2022, 23, 1532 its molecular mechanisms of action and treatment modalities including the combination therapy with natural products
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