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Received: 2024/01/25 | Accepted: 2024/08/17 | Published: 2024/09/20
Received: 2024/01/25 | Accepted: 2024/08/17 | Published: 2024/09/20
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Akhtar K, Baloch A, Kakar M. Phytochemicals as Safe Agents for the Prevention of Cancer. GMJM 2024; 3 (3) :107-111
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1- Livestock and Dairy Development Department Balochistan, Quetta, Pakistan
2- Director Planning and Development, L&DD Department, Spinny Road Quetta, Balochistan, Pakistan
2- Director Planning and Development, L&DD Department, Spinny Road Quetta, Balochistan, Pakistan
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Introduction
Cancer has been known as one of the genetic disorders [1] and also as the second cause of death in developed countries and/or even in developing countries [2]. The estimations have shown that cancer is almost the reason for 13% of total deaths, and its global distribution is variable in the different populations due to aging and the growth of the world population [3, 4]. It has been known by 100 types of cancer and classified by their cells [5]. It has been reported that 14.1 million new patients with cancer, except those with skin cancer other than melanoma [6]. It has been estimated to be 26 million new cases of cancer and 17 million cancer deaths yearly [7]. Despite significant progress, cancer has been yet known as an aggressive killer worldwide. Surgery, chemotherapy, and radiotherapy are common procedures for cancer treatment [8]. Such treatments have limitations such as side effects including fatigue, pain, diarrhea, nausea, vomiting, and hair loss [9] and could also cause gradual resistance of cancer cells against treatment [10]. It has been shown that half of cancer enduring in the United States exploits components derived from the various parts of plants or nutrients, singly and as adjuvant treatment alongside chemotherapy and/or radiation therapy [11-13]. From long years ago, natural herbal medicines have been applied in order to prevent and/or treat different diseases [14]. Phytochemicals make them appropriate for food consumers [15-17]. Studies have approved anticancer activities of phytochemicals [18-22]. Natural compounds of plants belonging to different groups, including alkaloids, diterpenes, diterpene quinone, purine-based compounds, lactonic sesquiterpene, peptides, cyclic depsipeptide, proteins, macrocyclic polyethers, etc. [23]. Some phytochemicals have been known to have anticancer activity, and on the other hand, modern medicine lacks effective drugs against certain types of cancers, including metastatic pancreatic adenocarcinoma and castration-resistant prostate cancer [23].
In this review article, we describe the use of phytochemicals for cancer prevention, review the previously published studies and present implications for this use.
A brief of phytochemicals
The Greek term “phyto” in phytochemicals originated from plants [24, 25]. Phytochemicals have been defined as bioactive, non-nutrient, and naturally present in plant compounds, which are found especially in fruits, vegetables, and whole grains. It has been estimated that there are 5000 special phytochemicals in grains, fruits, and vegetables, but many are not yet known and must be known before understanding the health advantages of whole foods [26]. Phytochemicals present in plant substances have increased interest among researchers in food production, the pharmaceutical industry, and/or their use in the prevention of human health. They are divided into different groups, including polyphenols, organosulfur compounds, carotenoids, alkaloids, and nitrogen-containing compounds [27]. Some phytochemicals have also been known as effectors of biological processes and can influence disease risk through complementary and overlapping mechanisms [27]. Phytochemicals can penetrate and delay the promotion of multistep carcinogenesis [28] and postpone precancerous cells' progression into malignant ones [29, 30].
Phenolics
The phenolics as secondary metabolites are broadly found in plants, especially fruits [31]. They are known to have 1, 2, and/or more aromatic rings [32]. They have antioxidant properties and prevent against cancers. Their profitability could be attributed to their regular consumption and bioavailability [33]. They are precursors for flavonoids and tannins [34, 35]. Hydroxycinnamic acids and their derivatives in fruits and vegetables are derived from p-coumaric acid (PCA), caffeic acid (CA), and ferulic acid (FA) [36]. Flavonoids are the main class of phenolic structures with antioxidant activity [37]. Such phytochemicals are connected to decreasing the risk of main chronic diseases and are largely identified in fruits, vegetables, and other plant foods [38]. They are divided into flavonols, flavones, flavanols (catechins), flavanones, anthocyanidins, and isoflavonoids with one heterocyclic C ring [39]. The chemical structure of flavonoids relies on their functional group, rate of hydroxylation, other substitutions and conjugations, and rate of polymerization [40]. Functional hydroxyl groups in flavonoids act in antioxidant activity through scavenging free radicals and/or chelating metal ions [41, 42]. Flavonoids are placed in the nucleus of mesophyll cells and inside the centers of the reactive oxygen species group. Some possible mechanisms have been suggested for the effect of flavonoids in the initiation and encourage the stages of the carcinogenicity, such as effects on development and hormonal activities, including (1) Downregulation of mutant p53 protein, (2) Stopping cell cycle arrest, (3) Prevention of tyrosine kinase activity, heat shock proteins and expression of Ras proteins [43]. Organosulfur structures are known as organic structures that could be identified by their sulfur having functional groups [44]. Daily consumption of organosulfur components could improve bioactive characteristics, particularly in relation to cardiovascular health [26]. Some organosulfur components were evaluated based on their ability to prevent carcinogenesis promoted through N-nitroso diethylamine, and the best was observed in diallyl disulfide [45]. Some organosulfur structures in the Allium genus have been shown to have anti-cancer activity [46].
Carotenoids
Carotenoids are known as natural pigments which have received attention. More than 600 different carotenoids have been recognized in nature. They may be originated from plants, microorganisms, and/or animals. They have a skeleton of isoprene units containing 40-carbon [47]. Carotenoids can react with free radicals and produce radicals [48]. The α-carotene has been known to have strong protective factors. The β-carotene present in green leafy vegetables acts as an antioxidant, but it has prooxidant effects in high levels and particularly in high oxygen tension [2]. The antioxidant activity of carotenoids could be attributed to antioxidant activity.
Alkaloids
Alkaloids are a known class of ring compounds nitrogen with organic compounds with various anticancer properties [49]. Such structures have the activity of preventing cancer by inhibiting enzymes from topoisomerase activity that is involved in DNA imitation, induction of apoptosis, and gene expression of the p53 gene [50, 51]. Alkaloids have similar structures and neurotransmitters in the central nervous system of human beings. With regards to alkaloids and research in relation to their role in the treatment of wild propagation of cells, they have been used as an efficient chemo-preventive substance [52, 53]. Amaryllidaceae alkaloids, betalain alkaloids, diterpenoid alkaloids, indole alkaloids, isoquinoline alkaloids, lycopodium alkaloids, monoterpene and sesquiterpene alkaloids, peptide alkaloids, pyrrolidine and piperidine alkaloids, pyrrolizidine alkaloids, quinoline alkaloids, quinolizidine alkaloids, steroidal alkaloids, tropane alkaloids, and miscellaneous alkaloids have been known as the major class of Alkaloids [46]. Catharanthus alkaloids have been used as adjuvant treatment for chemotherapy in the treatment of breast cancer, ovarian cancer, non-small cell lung cancer, and soft tissue sarcoma (orphan). Catharanthus alkaloids have also been used for therapy of acute lymphocytic leukemia, malignant lymphomas such as Hodgkin’s lymphoma and non-Hodgkin’s lymphoma, multiple myeloma, idiopathic thrombocytopenic purpura, solid tumors, such as metastatic testicular cancer, Ewing’s sarcoma, fetal rhabdomyosarcoma, primary neuroectodermal tumors Wilms’ tumor, and retinoblastoma [23].
Mechanisms of phytochemicals for the prevention and treatment of cancer
Cancer has been known as one of several mechanism carcinogenesis processes, including several steps such as mutagenic, cell death, and epigenetic by associated stages: initiation, promotion, and progression [54, 55]. Cells in humans and other organisms are broadly found in a range of oxidizing agents that are essential for life in several cases [56, 57]. Carcinogenic substances, such as environmental pollutants, dietary mutagens, and radiation, will produce ROS and/or reactive nitrogen species (RNS) that react with cellular molecules such as proteins, lipids, and DNA for the promotion of carcinogenesis. Regular consumption of phytochemicals directly alleviates ROS/RNS levels and removes carcinogenic reactive intermediates through dietary phytochemicals intake not only scavenges ROS/RNS directly but also eliminates carcinogenic reactive intermediates indirectly transcription factor Nrf2 [nuclear factor erythroid2 p45 (NF-E2)-related factor 2] by involving with the antioxidant system. It has been accepted that if Nrf2 is to be released from Kelch-like ECH related to protein 1 (Keap1) and transferred into the nucleus, Nrf2 is associated with antioxidant responsive elements (AREs) in the promoter/enhancer site of step II detoxification and antioxidant enzyme genes with the Maf protein. On the other hand, the reactivation of Nrf2 could be corrected through the supplementation of phytochemicals through epigenetic modifications, including DNA methylation and histone correction.
Conclusion
Although cancer is very complex and certainly cannot be treated by nutrient interventions, the use of safe compounds such as phytochemicals can help to some extent in the treatment and prevention of cancer. Regular consumption of phytochemicals can prevent and decrease costs. We recommend daily use of phytochemicals for cancer prevention and treatment.
Acknowledgments: None declared by the authors.
Ethical Permission: None declared by the authors.
Conflicts of Interests: None declared by the authors.
Funding/Support: This research did not receive a specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Cancer has been known as one of the genetic disorders [1] and also as the second cause of death in developed countries and/or even in developing countries [2]. The estimations have shown that cancer is almost the reason for 13% of total deaths, and its global distribution is variable in the different populations due to aging and the growth of the world population [3, 4]. It has been known by 100 types of cancer and classified by their cells [5]. It has been reported that 14.1 million new patients with cancer, except those with skin cancer other than melanoma [6]. It has been estimated to be 26 million new cases of cancer and 17 million cancer deaths yearly [7]. Despite significant progress, cancer has been yet known as an aggressive killer worldwide. Surgery, chemotherapy, and radiotherapy are common procedures for cancer treatment [8]. Such treatments have limitations such as side effects including fatigue, pain, diarrhea, nausea, vomiting, and hair loss [9] and could also cause gradual resistance of cancer cells against treatment [10]. It has been shown that half of cancer enduring in the United States exploits components derived from the various parts of plants or nutrients, singly and as adjuvant treatment alongside chemotherapy and/or radiation therapy [11-13]. From long years ago, natural herbal medicines have been applied in order to prevent and/or treat different diseases [14]. Phytochemicals make them appropriate for food consumers [15-17]. Studies have approved anticancer activities of phytochemicals [18-22]. Natural compounds of plants belonging to different groups, including alkaloids, diterpenes, diterpene quinone, purine-based compounds, lactonic sesquiterpene, peptides, cyclic depsipeptide, proteins, macrocyclic polyethers, etc. [23]. Some phytochemicals have been known to have anticancer activity, and on the other hand, modern medicine lacks effective drugs against certain types of cancers, including metastatic pancreatic adenocarcinoma and castration-resistant prostate cancer [23].
In this review article, we describe the use of phytochemicals for cancer prevention, review the previously published studies and present implications for this use.
A brief of phytochemicals
The Greek term “phyto” in phytochemicals originated from plants [24, 25]. Phytochemicals have been defined as bioactive, non-nutrient, and naturally present in plant compounds, which are found especially in fruits, vegetables, and whole grains. It has been estimated that there are 5000 special phytochemicals in grains, fruits, and vegetables, but many are not yet known and must be known before understanding the health advantages of whole foods [26]. Phytochemicals present in plant substances have increased interest among researchers in food production, the pharmaceutical industry, and/or their use in the prevention of human health. They are divided into different groups, including polyphenols, organosulfur compounds, carotenoids, alkaloids, and nitrogen-containing compounds [27]. Some phytochemicals have also been known as effectors of biological processes and can influence disease risk through complementary and overlapping mechanisms [27]. Phytochemicals can penetrate and delay the promotion of multistep carcinogenesis [28] and postpone precancerous cells' progression into malignant ones [29, 30].
Phenolics
The phenolics as secondary metabolites are broadly found in plants, especially fruits [31]. They are known to have 1, 2, and/or more aromatic rings [32]. They have antioxidant properties and prevent against cancers. Their profitability could be attributed to their regular consumption and bioavailability [33]. They are precursors for flavonoids and tannins [34, 35]. Hydroxycinnamic acids and their derivatives in fruits and vegetables are derived from p-coumaric acid (PCA), caffeic acid (CA), and ferulic acid (FA) [36]. Flavonoids are the main class of phenolic structures with antioxidant activity [37]. Such phytochemicals are connected to decreasing the risk of main chronic diseases and are largely identified in fruits, vegetables, and other plant foods [38]. They are divided into flavonols, flavones, flavanols (catechins), flavanones, anthocyanidins, and isoflavonoids with one heterocyclic C ring [39]. The chemical structure of flavonoids relies on their functional group, rate of hydroxylation, other substitutions and conjugations, and rate of polymerization [40]. Functional hydroxyl groups in flavonoids act in antioxidant activity through scavenging free radicals and/or chelating metal ions [41, 42]. Flavonoids are placed in the nucleus of mesophyll cells and inside the centers of the reactive oxygen species group. Some possible mechanisms have been suggested for the effect of flavonoids in the initiation and encourage the stages of the carcinogenicity, such as effects on development and hormonal activities, including (1) Downregulation of mutant p53 protein, (2) Stopping cell cycle arrest, (3) Prevention of tyrosine kinase activity, heat shock proteins and expression of Ras proteins [43]. Organosulfur structures are known as organic structures that could be identified by their sulfur having functional groups [44]. Daily consumption of organosulfur components could improve bioactive characteristics, particularly in relation to cardiovascular health [26]. Some organosulfur components were evaluated based on their ability to prevent carcinogenesis promoted through N-nitroso diethylamine, and the best was observed in diallyl disulfide [45]. Some organosulfur structures in the Allium genus have been shown to have anti-cancer activity [46].
Carotenoids
Carotenoids are known as natural pigments which have received attention. More than 600 different carotenoids have been recognized in nature. They may be originated from plants, microorganisms, and/or animals. They have a skeleton of isoprene units containing 40-carbon [47]. Carotenoids can react with free radicals and produce radicals [48]. The α-carotene has been known to have strong protective factors. The β-carotene present in green leafy vegetables acts as an antioxidant, but it has prooxidant effects in high levels and particularly in high oxygen tension [2]. The antioxidant activity of carotenoids could be attributed to antioxidant activity.
Alkaloids
Alkaloids are a known class of ring compounds nitrogen with organic compounds with various anticancer properties [49]. Such structures have the activity of preventing cancer by inhibiting enzymes from topoisomerase activity that is involved in DNA imitation, induction of apoptosis, and gene expression of the p53 gene [50, 51]. Alkaloids have similar structures and neurotransmitters in the central nervous system of human beings. With regards to alkaloids and research in relation to their role in the treatment of wild propagation of cells, they have been used as an efficient chemo-preventive substance [52, 53]. Amaryllidaceae alkaloids, betalain alkaloids, diterpenoid alkaloids, indole alkaloids, isoquinoline alkaloids, lycopodium alkaloids, monoterpene and sesquiterpene alkaloids, peptide alkaloids, pyrrolidine and piperidine alkaloids, pyrrolizidine alkaloids, quinoline alkaloids, quinolizidine alkaloids, steroidal alkaloids, tropane alkaloids, and miscellaneous alkaloids have been known as the major class of Alkaloids [46]. Catharanthus alkaloids have been used as adjuvant treatment for chemotherapy in the treatment of breast cancer, ovarian cancer, non-small cell lung cancer, and soft tissue sarcoma (orphan). Catharanthus alkaloids have also been used for therapy of acute lymphocytic leukemia, malignant lymphomas such as Hodgkin’s lymphoma and non-Hodgkin’s lymphoma, multiple myeloma, idiopathic thrombocytopenic purpura, solid tumors, such as metastatic testicular cancer, Ewing’s sarcoma, fetal rhabdomyosarcoma, primary neuroectodermal tumors Wilms’ tumor, and retinoblastoma [23].
Mechanisms of phytochemicals for the prevention and treatment of cancer
Cancer has been known as one of several mechanism carcinogenesis processes, including several steps such as mutagenic, cell death, and epigenetic by associated stages: initiation, promotion, and progression [54, 55]. Cells in humans and other organisms are broadly found in a range of oxidizing agents that are essential for life in several cases [56, 57]. Carcinogenic substances, such as environmental pollutants, dietary mutagens, and radiation, will produce ROS and/or reactive nitrogen species (RNS) that react with cellular molecules such as proteins, lipids, and DNA for the promotion of carcinogenesis. Regular consumption of phytochemicals directly alleviates ROS/RNS levels and removes carcinogenic reactive intermediates through dietary phytochemicals intake not only scavenges ROS/RNS directly but also eliminates carcinogenic reactive intermediates indirectly transcription factor Nrf2 [nuclear factor erythroid2 p45 (NF-E2)-related factor 2] by involving with the antioxidant system. It has been accepted that if Nrf2 is to be released from Kelch-like ECH related to protein 1 (Keap1) and transferred into the nucleus, Nrf2 is associated with antioxidant responsive elements (AREs) in the promoter/enhancer site of step II detoxification and antioxidant enzyme genes with the Maf protein. On the other hand, the reactivation of Nrf2 could be corrected through the supplementation of phytochemicals through epigenetic modifications, including DNA methylation and histone correction.
Conclusion
Although cancer is very complex and certainly cannot be treated by nutrient interventions, the use of safe compounds such as phytochemicals can help to some extent in the treatment and prevention of cancer. Regular consumption of phytochemicals can prevent and decrease costs. We recommend daily use of phytochemicals for cancer prevention and treatment.
Acknowledgments: None declared by the authors.
Ethical Permission: None declared by the authors.
Conflicts of Interests: None declared by the authors.
Funding/Support: This research did not receive a specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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