Natural Isolated Compound Used for Treatment of Colorectal Cancer

NATURAL ISOLATED COMPOUND USED FOR TREATMENT OF COLORECTAL CANCER. Author’s – Prajakta Gaikwad1st*, Vaishali S. Payghan2nd, Lalita Dahiwade3rd, Suraj Jadhav4th, Santosh A. Payghan5th. Student1st, Asst. Professor2nd Professor3nd, Professor4nd, Professor5nd Department of Pharmaceutics Vasantidevi Patil Institute of Pharmacy, Kodoli Tal- Panhala, Dist – Kolhapur (MH) 416114 Abstract:

We describe here the main natural ingredients used for cancer treatment and prevention, the historical features of their application and pharmacognosy. Two major applications of these compounds are described: such as cancer treatment and chemotherapy. Both natural and synthetic compounds, either derived from plants or animals or produced by antibiotics, and synthetic compounds, derived from natural extracts, are used. Other current critical aspects of cancer chemistry are also being discussed, focusing on genes and genes, as well as the latest cancer-changing concept: aneuploidy as the premium movens of cancer.

Keyword - Colorectal Cancer, Alkaloid, Chitin, Polysaccharide.

Introduction: play an important role in cancer treatment Evidence of cancer has been found in today with the large number of anticancer ancient fossils and in medical literature agents used clinically natural or found in from antiquity, from the time of Pharaoh in natural products from a variety of sources ancient Egypt to the ancient world. such as plants, animals and micro- Although it is difficult to interpret the organisms (also from the sea) (Fig. 1). diagnosis of doctors who live hundreds of Major cancer drug detection programs and years ago, we can assume that many of screening programs such as those promoted their explanations are related to cancer by the National Cancer Institute (NCI) have cases. Ancient medical literature reports played an important role in the that surgery was performed but doctors also development of natural cancer-causing recommended the use of certain natural chemicals. Over the past few years, the products, especially plant products, which availability of natural product drugs has represent an interesting comparison point increased with new technologies, such as with current knowledge. Natural products combination and advanced testing, as well IJCRT2103574 International Journal of Creative Research Thoughts (IJCRT) www.ijcrt.org 4991 www.ijcrt.org © 2021 IJCRT | Volume 9, Issue 3 March 2021 | ISSN: 2320-2882 as their compatible methods. Vincristine, Alkaloids are a class of basic chemicals, irinotecan, etoposide and paclitaxel are naturally occurring to contain at least one ancient examples of genes associated with nitrogen atom. The group also included plants; actinomycin D, mitomycin C, other neutral-related factors [2] and weak bleomycin, doxorubicin and l-asparaginase structures. [3] Other synthetic compounds are drugs derived from bacterial sources, of the same structure can also be called and citarabine is the first drug from a alkaloids. marine source. To date, new generations of Classifications: taxis, anthracyclines, Vinca alkaloids, The nicotine molecule contains both camptothecins, and the novel category of pyridine (left) and pyrrolidine rings. epothilones have been developed. Some of Compared to other natural chemical them are used for clinical use, others are compounds, alkaloids are characterized by used for clinical trials. Other agents from excellent structural diversity. There is no marine resources (both plants and animals) parallelism. Initially, when genetic (e.g. trabectedin-ET-743, bryostatin-1, knowledge was in short supply, plant neovastat) also participated in clinical trials. extracts were relied upon. This category is All of these drugs are characterized by a now considered obsolete.Recent categories variety of mechanisms, including have been based on the similarity of carbon microtubules, inhibition of topoisomerases sequestration (e.g., however, they need to I or II, DNA alkylation, and impaired signal be relaxed in boundary cases; can be transplantation. This review describes the assigned to both classes. Alkaloids are key natural compounds used in cancer usually classified into the following major treatment and prevention. These factors groups: have been synthesized and updated with a 1. “True alkaloids” contain nitrogen in the focus on the latest information on cellular heterocycle and are derived communication factors and their cellular amino acids. Their human examples are targets, from DNA to microtubules. Other atropine, nicotine, and current critical aspects of cancer cancer morphine. This group also includes chemistry are also highlighted, as well as alkaloids other than the nitrogen these more recent cancer mutations: where heterocycle that contain terpene (e.g., not genetic cancer mutations but genetics Evonine). or peptide fragments (e.g. and / or aneuploidy are the onset of cancer. ergotamine). The piperidine alkaloids A natural product that acts as a drug against coniine and coniceine may be regarded as the CRC in a clinical setting: true alkaloids (rather than pseudoalkaloids: Alkaloid: see below) although they do not originate from amino acids. 2. "Protoalkaloids", which contain nitrogen (but not the nitrogen heterocycle) and also originate from amino acids.Examples include mescaline, adrenaline and ephedrine. 3. Polyamine alkaloids - derived from putrescine, spermidine, and spermine. 4. The alkaloids of Peptide and cyclopeptide.

5. Pseudoalkaloids - alkaloid-like chemicals quinine sulfate. Many alkaloids have a that do not come from amino acids. This bitter or toxic taste when ingested. Alkaloid group includes alkaloids such as terpene production in plants appears to have shifted and steroids, as well as purine alkaloids to a nutrient response by such as caffeine, theobromine, theacrine predators; however, some animals have and theophylline. Some authors classify it shifted their ability to release toxins from as pseudoalkaloids chemical compounds alkaloids. Some alkaloids can produce such as ephedrine and cathinone. Those are developmental defects in predatory animals derived from the amino acid phenylalanine, but cannot detoxify alkaloids. One example but derive a nitrogen atom not from an is the alkaloid cyclopamine, which is amino acid but by conversion. Some produced from maize leaves. In the 1950's, alkaloids do not have carbon up to 25% of lambs born from lambs that the skeletal aspect of their group. had been fed corn on the cob had serious Therefore, galanthamine and facial features. These ranged from homoaporphines do not contain traces of paralyzed jaws to cyclopia. After decades isoquinoline, but, more commonly, are of research, in the 1980's, the company caused by isoquinoline alkaloids. responsible for this disability was identified Features: as alkaloid 11 deoxyjervine, later called Many alkaloids contain oxygen in their cyclopamine. cellular structures; those compounds Applications: usually contain colorless crystals in the In medicine The use of alkaloid-containing existing conditions. Oxygen-free alkaloids, plants has a long history, so, when the first such as nicotine or coniine, are usually alkaloids were isolated in the 19th century, liquid, colorless, and oily. A head of a they quickly found the use of alternative sheep born from a sheep that ate the leaves therapies. are designed to enhance or of the corn lily plant. Cyclopia is caused by reverse the main effect of a drug and to the cyclopamine present in the plant. minimize unwanted side effects. [208] For colored alkaloids, such as berberine example, naloxone, an opioid receptor (yellow) and sanguinarine (orange). antagonist, is based on thebaine present in Many alkaloids are weak foundations, but opium. some, such as theobromine and 2. Polysaccharide: theophylline, are amphoteric. Many Polysaccharides polycarhydrate, the most alkaloids are soluble in water but are easily abundant carbohydrate found in food. They soluble in natural solvents, such as diethyl are many polymeric carbohydrates ether, chloroform or 1,2-dichloroethane. composed of monosaccharide units Caffeine, cocaine, [163] codeine and composed of glycosidic bonds. This nicotine are soluble in water (with ≥1g / L carbohydrate can react with water solubility), and (hydrolysis) using amylase enzymes such others, including morphine and yohimbine as catalyst, which produces sugar are very small amounts of water (0.1-1 g / (monosaccharides, or oligosaccharides). L). Alkaloids and acids form salts of They vary in structure from row to large various strengths. These salts are usually branches. Examples include starch soluble in water and ethanol and are polysaccharides, starch, glycogen and insoluble in most solvents. Variations galactogen and structural polysaccharides include scopolamine hydrobromide, soluble such as cellulose and chitin. in organic solvents, and wateroluble IJCRT2103574 International Journal of Creative Research Thoughts (IJCRT) www.ijcrt.org 4993 www.ijcrt.org © 2021 IJCRT | Volume 9, Issue 3 March 2021 | ISSN: 2320-2882

Function: dissolve in water. They can be digested by Nutrient polysaccharides are common breaking down alpha connections sources of energy. Many organic matter can (glycosidic bonds). Both humans and easily digest starch into sugar; however, animals have amylases, so they can digest many organisms cannot use cellulose or starch. Potatoes, rice, wheat, and corn are other polysaccharides such as chitin and the main sources of starch in the human arabinoxylans. These types of diet. The composition of starch is the way carbohydrates may be synthesized by plants store sugar. certain bacteria and protists. Ruminants and Glycogen: termites, for example, use microorganisms Glycogen acts as a second long-term energy to process cellulose. Although these storage in animal and fungal polysaccharides are very complex, they cells, which have the main energy stores provide essential nutrients for humans. captured by adipose tissue. Glycogen is Called dietary fiber, these carbohydrates mainly produced by the liver and muscles, increase digestion among other benefits. but can also be produced by glycogenesis The main action of dietary fiber is to alter within the brain and stomach. Glycogen is the contents of the intestinal tract, and to similar to starch, a polymer glucose in change the way other nutrients and plants, and is sometimes called animal chemicals are absorbed. Soluble fiber binds starch, which has the same structure as to bile acids in the small intestine, making amylopectin but has more branches and them less likely to enter the body; this in compounds than starch. Glycogen is a turn lowers blood cholesterol levels. polymer α (1 → 4) glycosidic bonded, with Soluble fiber also reduces sugar absorption, α-connected branches (1 → 6). Glycogen is reduces postprandial sugar response, makes found in the form of granules in the cytosol normal blood lipid levels and, once mature / cytoplasm in many cell types, and plays in the colon, produces low-chain acids such an important role as organic products (discussion below). glucose cycle. Glycogen forms energy Although uncontrolled fiber is associated storage that can be used immediately with a reduced risk of diabetes, the to meet the unexpected demand for glucose, mechanism by which this occurs is but less common and more readily available unknown. It has not yet been officially as energy storage than triglycerides (lipids). recognized as an important macronutrient In the hepatocyte of the liver, glycogen can (since 2005), dietary fiber is considered an absorb up to 8 percent (100-120 grams in important dietary supplement, with adult) of new weight immediately after a regulatory authorities in many developed meal. Only glycogen stored in the liver can countries recommending increased dietary be made available to other organs. In fiber intake. Storage of polysaccharides muscle, glycogen is found in less than one Starch. units bound by alpha connection. It to two percent muscle filter. The amount of is made with a mixture of amylose (15- glycogen stored in the body - especially 20%) and amylopectin (80-85%). Amylose within the muscles, liver, and red blood contains the corresponding series of several cells varies with exercise, basal metabolic hundred glucose molecules, and rate, and eating habits such as periodic Amylopectin is a branched particle made up fasting. A small amount of glycogen is of several thousand units of sugar (the found in the kidneys, as well as small whole series of 24-30 units of glucose is amounts in certain glial cells in the brain one unit of Amylopectin). Starch does not and in white blood cells. The uterus also IJCRT2103574 International Journal of Creative Research Thoughts (IJCRT) www.ijcrt.org 4994 www.ijcrt.org © 2021 IJCRT | Volume 9, Issue 3 March 2021 | ISSN: 2320-2882 retains glycogen during pregnancy, feeding containing bacteria in their gut. Cellulose is the fetus.Glycogen is made up of a series of waterless. It does not change color when branches of glucose residues. It is stored in mixed with iodine. In hydrolysis, it the liver and muscles. produces glucose. The most abundant • It is an energy reserve for animals. carbohydrate in nature. • It is the main source of carbohydrate Chitin: stored in the animal's body. Chitin is one of the most naturally • It does not dissolve in water. Turns occurring polymers. It forms part of the reddish brown when mixed with iodine. structure of many animals, such as • It also produces glucose in hydrolysis exoskeletons. Over time the environment Galactogen: diminishes. Its breakdown may be caused Galactogen is a galactose polysaccharide by enzymes, which are secreted by that acts as a storage energy for pulmonate microorganisms such as bacteria and fungi snails and other Caenogastropods. This and are produced by other plants. Some of polysaccharide is only for production and is these tiny insects have simple sugar only found in the albumen gland from the receptors from chitin decay. When chitin is reproductive system of the female snail and detected, they then produce enzymes that the perivitelline egg yolk. Galactogen acts break it down by removing glycosidic as an energy storage device for the bonds to convert it into light sugars and development of embryos and nodules, ammonia. Chemically, chitin is closely which are later replaced by glycogen in related to chitosan (based on water-soluble children and adults. chitin). It is also closely related to cellulose Insulin: because it is a long offline option for Galactogen is a galactose polysaccharide glucose products. that acts as a storage energy for pulmonate 3.Polyphenol: snails and other Caenogastropods. This The term polyphenol is not well defined, polysaccharide is only for production and is but it is generally agreed that it is natural only found in the albumen gland from the products "with a polyphenol structure (e.g., reproductive system of the female snail and many hydroxyl groups in perfumed rings" the perivitelline egg yolk. Galactogen acts include four main classes: "phenolic acid, as an energy storage device for the flavonoids stilbenes, and lignans" development of embryos and nodules, Flavonoids include flavones, flavonols, which are later replaced by glycogen in flavanols, flavanones, isoflavones, children and adults. proanthocyanidins, and anthocyanins. The Cellulose: most common flavanoids in the diet are The nutrients in plants are made mainly catechin (tea, fruit), hesperetin (citrus from cellulose. Wood fruits), cyanidin (red fruits and berries), especially cellulose and lignin, while paper daidzein (soy), proanthocyanidins (apple, and cotton are almost pure cellulose. grapes. , cocoa) and quercetin (onions, tea, Cellulose is a polymer made up of repeated apples). glucose units that are glued together with Phenolic acid contains caffeic acid betalinkages. Most people and animals do Lignans polyphenols derived from not have the enzyme that breaks down beta phenylalanine are found in flax seeds and interactions, so they do not digest cellulose. other grains. Certain animals, such as termites, can digest cellulose, since they have enzyme- IJCRT2103574 International Journal of Creative Research Thoughts (IJCRT) www.ijcrt.org 4995 www.ijcrt.org © 2021 IJCRT | Volume 9, Issue 3 March 2021 | ISSN: 2320-2882 Structure and biosynthesis: Mechanism underlying the action of Structural features: potential natural product based Polyphenols are usually large molecules drugs against CRC: (macromolecules). Their molecular weight 1 proliferation based regulation limit is about 800 Daltons, allowing them to 2 migration and invasion based regulation spread rapidly throughout the cell 3 apoptosis based regulation membrane so that they can access sites of 4 autophagy based regulation intracellular activity or remain as pigs once 5 angiogenesis based regulation the cell cells are still in the cells. Therefore, many polyphenols are large 1. Proliferation based regulation in-situ biosynthesized from small polyphenols to non-hydrolyzable tannins a) Nuclear proliferation: and remains unavailable in plant matrix. The proliferation of nuclear weapons is the Most polyphenols contain phenolic proliferation of nuclear weapons, inputs, compounds of phenolic moitions of and nuclear technology used in weapons in pyrocatechol, resorcinol, pyrogallol, and countries known as the "Nuclear Weapon phloroglucinol linked to esters (non- States" by the Treaty on the Non- hydrolyzable tannins) or stable CC bonds Proliferation of Nuclear Weapons, also (tannins containing non-hydrolyzable known as the Non-Proliferation Treaty or condensed). Proanthocyanidins are mainly NPT. The increase has been opposed by units of catechin and epicatechin. many nations with and without nuclear Polyphenols tend to have more active weapons, as governments fear that more groups than hydroxyl groups. Ether ester nuclear powers will increase the risk of interactions are common, as are carboxylic nuclear war (up to the so-called acids. countervalue targeting of civilians with Chemical properties: nuclear weapons), de-stabilize international Polyphenols are reactive species toward or regional relations, or violate them. world oxidation, hence their description as empire. antioxidants in vitro. Dual use technology: Uses: Double-use technology refers to the Some polyphenols are traditionally used as possible military use of public-sector dyes. For example, in India power. Many of the technologies and on the continent, pomegranate peel, which materials associated with the development is high in tannins and other polyphenols, or of the Dual use technology system for juice, employed in the dyeing of unused nuclear power have double power, because fabrics. Polyphenols, especially tannins, are several phases of the nuclear fuel cycle traditionally used to tan the skin and even allow for the separation of nuclear material. today and as precursors of raw chemistry When this happens the nuclear power specifically to produce plastics or fractions system can be the path that leads to the by applying polymerization with or without atomic bomb or the public annex to a secret the use of formaldehyde or adhesive bomb system. The crisis in Iran's nuclear particleboards. Targets usually use plant activities is an example of this. residues from grapes, olives (called pomaces) or pecan shells left over after processing. Pyrogallol and pyrocatechin are among the oldest photo developers. IJCRT2103574 International Journal of Creative Research Thoughts (IJCRT) www.ijcrt.org 4996 www.ijcrt.org © 2021 IJCRT | Volume 9, Issue 3 March 2021 | ISSN: 2320-2882 b) Cell proliferation: cell growth during the process of cell Cell proliferation is the process by which a proliferation, when a cell, known as a cell grows and divides to produce two "mother cell", grows and divides to produce daughter cells. Cell proliferation leads to a two "daughter cells". cell growth and cell clear growth of cell numbers and is division can also occur independently of therefore the fastest way to grow tissue. each other. During early embryonic Cell proliferation requires that cell growth development (the division of the zygote to and cell division take place simultaneously, form a morula and blastoderm), cell as cell proliferation remains constant in division occurs more frequently without humans. Cell division is possible without cell growth. cell growth, producing more slow-moving 2. migration and invasion based cells (such as in zygote purification, while regulation: cell growth can occur without cell division Human migration Migration involves the to produce one larger cell (such as growth) movement of people from one place to senses). Therefore, cell proliferation is not another for the purpose of settling, the same as cell growth or cell growth permanently or temporarily, in a new place Separation, except that these words are (local region). Movement usually occurs sometimes used interchangeably. over long distances and from one country to Stem cells experience cell proliferation to another, but internal migration (in one produce increasing “growth” country) is also possible; indeed, this is an daughter cells later divide to form tissue outstanding form of global migration. during normal growth and tissue growth, Migration is often associated with better during tissue regeneration after injury, or in human structure at individual and home cancer. The total number of cells in humans levels, as well as better access to migration is determined by the rate of cell networks. Age is also very important for proliferation minus the number of cell job migration and unemployment. People deaths. Cell size depends on cell growth can move as individuals, in groups of and cell division, with an unequal increase families or in large groups. There are four in the rate of cell growth leading to mass main types of migration: invasion, cell production and an unequal increase in conquest, colonization and emigration. cell division that leads to mass production. Immigrants are traditionally defined as small cells. Cell proliferation usually people who change the country they live in involves the moderate growth of cells and for common reasons and purposes. These the levels of cell division that maintain a objectives may include a search for better stable cell size in increasing cell numbers. job opportunities or health needs. This term c) Cell growth: is the one most often interpreted as anyone Cell growth means an increase in the total who permanently changes his place can be weight of a cell, including the cytoplasmic, considered an immigrant. nuclear and organelle volumes. Cell growth 3. Apoptosis Based Regulation: occurs when the overall level of cellular Apoptosis is a form of programmed cell biosynthesis (biomolecule production or death thatoccurs in multicellular anabolism) is greater than the total rate of organisms.Biochemical events lead to cellular decline (destruction of biomolecule characteristic cell changes (morphology) by proteasome, lysosome or autophagy, or and death.These changes include blebbing, catabolism). by cell division or cell cycle, cell shrinkage, nuclear fragmentation, which is a different process possible and chromatin condensation, chromosomal IJCRT2103574 International Journal of Creative Research Thoughts (IJCRT) www.ijcrt.org 4997 www.ijcrt.org © 2021 IJCRT | Volume 9, Issue 3 March 2021 | ISSN: 2320-2882

DNA fragmentation, and global mRNA used in clinical practice.Nature is still today decay. The average adult human loses a rich source of effective mechanisms that between 50 and 70 billion cells each day fight cancer cells. Natural chemicals due to apoptosis. For an average human contain old cytotoxic categories targeting child between the ages of 8 and 14, different and specific macromolecules approximately 20–30 billion cells die per identified by cancer cells and to a lesser day.Activation mechanisms.The initiation extent by normal growing cells (e.g. DNA, of apoptosis is tightly regulated by enzymes, microtubules) or new chemicals activation mechanisms, because once targeting macromolecules eg another apoptosis has begun, it inevitably leads to appropriate field for the use of natural the death of the cell. The two best- chemicals is cancer chemoprevention understood activation mechanisms are the because these compounds can inhibit intrinsic pathway (also called the certain processes involved in mitochondrial pathway) and the extrinsic cancerogenesis.Even a popular press often pathway.The intrinsic pathway is activated publishes articles on chemoprevention by intracellular signals generated when cancer and its potential benefits and cells are stressed and depends on the regularly reports on newly available natural release of proteins from the intermembrane exotic chemicals. However, although there space of mitochondria. The extrinsic is a strong molecular basis for this strategy, pathway is activated by extracellular the preoperative data and clinics in this ligands binding to cell-surface death field are still limited and no controlled receptors, which leads to the formation of clinical research has been published the deathinducing signaling complex showing the benefits in are suitable for (DISC). clinical practice. It is important to emphasize that only intensive pre-surgery 4 Autophagy: and clinical studies and an accurate Autophagy (or autophagocytosis) (from the understanding of the new chemical Greek autóphagos, meaning "devouring" chemistry can ensure the selection of an and κύτος kýtos, meaning "vain") is a effective and safe anticancer and natural, controlled process of a cell that chemopreventive drugs, including natural removes unwanted or inactive substances. compounds. Allows for systematic damage and cell renewal. 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IJCRT2103574 International Journal of Creative Research Thoughts (IJCRT) www.ijcrt.org 4999 www.ijcrt.org © 2021 IJCRT | Volume 9, Issue 3 March 2021 | ISSN: 2320-2882 proteins (MAPs) is due to increase in 2001;7:1181–97. frequency of rescue in dynamic instability: 25] Yun-San Yip A, Yuen-Yuen Ong E, shortening length decreases with binding of Chow LW. Vinflunine: clinical MAPs onto microtubules. perspectives Cell Struct Funct 1994;19:279–90. of an emerging anticancer agent. Expert 24] Fahy J. Modifications in the “upper” Opin Investig Drugs 2008;17:583–91, velbenamine part of the Vinca alkaloids doi:10.1517/13543784.17.4.583. have major implications for tubulin interacting activities. Curr Pharm Des

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