A Review on the Potential Application of Medicinal Species from Asteraceae Family in Cancer

Globally cancer is one of the most prevalent life-threatening diseases that have a significant impact on humans. The uncontrolled division of cells is a sign of the disease. Modern cancer therapies have several side effects on healthy cells. The problem of increasing tumour resistance to existing drug treatments is a serious concern. As a result, there is a critical need for more effective medicine to combat this condition. New ways to avoid this illness are in high need. Humans' pursuit of health is a never-ending drive for a healthier, longer life. Despite this, sickness and pain are still a part of his battle for survival. Natural products have a significant role in the battle against cancer and can be used to test novel therapeutic agents. Plants are natural remedies for a variety of illnesses. It is important to identify a variety of therapeutic plants which are useful for human being. Herbal therapies are a viable alternative to conventional cancer treatments. This article looks at plants from the Asteraceae family that have anticancer properties. Plants of the Asteraceae family play an important role in combating malignancies of the stomach, breast, colon, and lung, according to a thorough examination of research papers. The results of the study indicated a spectacular outcome in the prevention of cancer. Review Article Baile et al.; JPRI, 33(38A): 75-88, 2021; Article no.JPRI.70920 76


INTRODUCTION
Cancer is a terminal illness. There are indeed several illnesses. One of the issues is this. Several beginnings cause, cofactors and promoters, and types of cellular harm done on the body's cells are all present. Cancer is caused by cells in the body that were once healthy. These altered cells continue to divide in an uncontrollable rate. They vary from the cells in the regular tissue from whence they develop just slightly at first. As a result, cancer cells's biochemistry and molecular regulatory systems are comparable to those of the body's cells.
In a bacterial infection, an invading Staphylococcus recognises itself as a foreign organism, whereas cancer does not. It this true that, the body may develop a partial immune response against cancer cells, but these immune systems responses become suppressed and ineffective as the disease develops. Lymphocytic leukaemia, Hodgkin's disease, Burkitt's lymphoma, bone cancer, kidney cancer, muscle tissue cancer, testicular cancer,4. specific ovarian cancer and oestrogenic sarcoma are among the four forms of cancer. Every year, about one million people in India are diagnosed with cancer. Each year in India more than one million people are diagnosed with cancer. Each year, over 500,000 individuals succumb to cancer. The sickness will affect as many households as possible. Aside from the individual physical and mental toll, there is a significant financial toll on both the family and the country [1].

CANCER BIOLOGY
Cancer is caused by a multistep process in which cells accumulate genetic abnormalities, especially in oncogenes and tumour suppressor genes that lead to uncontrolled growth. These anomalies bring several development advantages. During the shift from normal cells to tumour cells, mutations in the cell genome are widespread. According to Harahan and Weinberg, six major alterations occur during the transition from a normal cell to a tumour cell, and these characteristics are referred to as cancer hallmarks [2].

Fig. 1. Sustained proliferative signaling [3]
Proliferation is a crucial aspect of cancer growth and progression. Cell cycle-related proteins' expression or activity are changed as a result of this. The stimulation of multiple signal transduction pathways on a continuous basis also promotes cell development. Early stages of tumor formation are linked to a fibro genic response and the establishment of a hypoxic environment that favours cancer stem cell survival and multiplication. Changes in cell metabolism may be part of cancer stem cells' survival strategy. Overproduction of relevant hormones, increasing angiogenesis, and undergoing epithelial to mesenchyme transition may encourage tumor development and spread once they occur. [4].
The TP53 gene produces the p53 tumour suppressor protein in humans. P53 suppresses abnormal growth in normal cells in part by interacting with the proapoptotic protein Bax, while mutations in the TP53 gene cause tumour suppression, loss of interaction with Bax, and apoptosis inhibition in cancer cells. Apoptosis, also known as programmed cell death, is a defensive process that prevents normal cells from being damaged or collecting mutations [4].
Telomerase activity is generally elevated in cancer cells. This allows them to become immortal, meaning they may divide eternally as long as their nutritional and oxygen needs are supplied. Proper cells divide for a finite number of replications and have normal telomere lengths [7].
To fuel their development, cancer cells need to consume more energy. Tumour cells primarily employ glycolysis rather than mitochondrial oxidative phosphorylation, therefore they must consume more glucose than normal cells. Furthermore, hypoxic circumstances and Ras expression upregulate glycolysis by increasing the expression of HIF1 and HIF2. HIF1 and HIF2 also stimulate the production of growth and angiogenic factors [9].
Changes in tumor-suppressing signalling proteins, such as p53, cause tumour cells to proliferate indefinitely. Another method that drives tumour cell proliferation is the escape from growth-suppressing signalling. In cancer cells, mutations in tumour suppressor genes are common: for example, p53 is often altered and affects the cell cycle in tumour cells [11].

Asteraceae Family
In the battle against illnesses, natural commodities play a crucial role. Even with recent advances in drug discovery methods like highthroughput screening, combinatorial chemistry, and rational drug design, these products were and continue to be a key source of early medicines. Natural materials are recognised as significant sources of lead compounds and new drug development potential since bench top chemical methods cannot achieve the molecular and structural variability of natural products. Sesquiterpene, found in the Asteraceae family, have a variety of biological effects, including cytotoxicity. [11] Plants in the Asteraceae family are considered good sources of chemopreventive agents because they contain a wide range of antioxidant molecules [12].
With over 23,000 species found on every continent except Antarctica, Asteraceae is one of the largest plant families. The capitulum, or flower heads, is a highly compressed inflorescence branch system in which all the flowers are attached to a receptacle covered by involucral bracts and is the most distinctive feature of the Asteraceae family. As seen in Fig.  6 for gerbera and sunflower, the capitulum produces a pseudanthium, which resembles a single massive bloom. Two other characteristics that are diagnostic for the family are anthers united in a tube and inferior ovary placement. Pappus bristles are produced from the outer floral whorl [14]. Some of the interested medicinal plants having potential anticancer activity belongs to Asteraceae family are mentioned in Table 1.

Anticancer Plants
 Achillea species Achillea millefolium has been used to treat haemorrhoids, cancer, vertigos, anaemia, anorexia, dyspepsia, gastralgia, haemorrhage, and Achillea bibersteinii has been collected from East Azerbaijan of Iran [15].and assayed on six cancerous cell lines, AGS human Caucasian gastric adenocarcinoma, SKLC6 human breast ductal carcinoma, SW741 human colorectal adenocarcinoma, SkLC6 human carcinoma, A375 human melanoma cancer cell and human liver hepatoma. In addition, complementary tests were used to confirm the selectivity of herbal extracts. In comparison to their cytotoxicity effects on many carcinogenic cells, herbal extracts have a lower haemolytic capacity and antifungal test results, which might indicate that they have effects in producing cytotoxicity in human carcinogenic cells [16].

 Achyrocline bogotensis
The family Asteraceae and the genus Gnaphalium are responsible for these plants [17]. These annuals or perennials reach a height of 1.5 metres and grow between 2000 and 3200 metres above sea level. They are readily mistaken with species belonging to different 78 were used to confirm the selectivity of herbal extracts. In comparison to their cytotoxicity effects on many carcinogenic cells, herbal extracts have a lower haemolytic capacity and antifungal test results, which might indicate that they have effects in producing cytotoxicity in The family Asteraceae and the genus Gnaphalium are responsible for these plants [17]. These annuals or perennials reach a height of 1.5 metres and grow between 2000 and 3200 metres above sea level. They are readily en with species belonging to different genera because of their physical features. These genera are widely utilised for therapeutic purposes in many areas of the world [18]. As a result, several Achyrocline species are used in poultices to treat wounds, act as a haemostatic, combat infections, and reduce inflammation. It is suggested in the Andean areas for cancer treatment. He described the cytotoxic effects of two flavone isomers on human cancer cells from the breast (MCF7, SK-BR-3), colon (Caco HCT116), and pancreatic (MCF7, SK (MIAPaCa, Pan28). The differentiation state and tumorigenic potential of these cells vary. These Asteraceae, namely the Achyrocline genus, are thought to have anticancer characteristics [19].

Fig. 3. Replicative immortality [6]
; Article no.JPRI.70920 genera because of their physical features. These genera are widely utilised for therapeutic purposes in many areas of the world [18]. As a result, several Achyrocline species are used in as a haemostatic, combat infections, and reduce inflammation. It is suggested in the Andean areas for cancer treatment. He described the cytotoxic effects of two flavone isomers on human cancer cells from 3), colon (Caco-2, , and pancreatic (MCF7, SK-BR-3) (MIAPaCa, Pan28). The differentiation state and tumorigenic potential of these cells vary. These Asteraceae, namely the Achyrocline genus, are thought to have anticancer characteristics [19].

Fig. 6. Flower heads in Gerbera hybrid and Helianthus annu  Ageratum conyzoides
The family Asteraceae includes Ageratum screen Conyzoides. It's common in Central America, the Caribbean, the United States, and Southeast Asia, including India [20,21]. It's known as "ufu opioko" [22]. It has anticancer properties and is used colds, rheumatism, headaches, and wounds [23,24]. Plant-based natural products might also be a good place to look for anticancer and antioxidant compounds.

 Ambrosia peruviana
Although the genus Plagiochila hundreds of species there have been no previous pharmacological or phytochemical findings on this species to our knowledge. Ambrosia peruviana is a South American plant whose extract is the subject of two patents, one of which refers to its appli

Flower heads in Gerbera hybrid and Helianthus annu [13]
The family Asteraceae includes Ageratum screen Conyzoides. It's common in Central America, the Caribbean, the United States, and Southeast Asia, including India [20,21]. It's known as "ufu opioko" [22]. It has anticancer properties and is used to treat colds, rheumatism, headaches, and wounds based natural products might also be a good place to look for anticancer and antioxidant compounds. The sulphorhodamine B (SRB) assay was used to test the in vitro activity of ethanol and troleum ether extracts of Ageratum in cancer cell lines. Human non--549), human -29), human 251), human breast 231), and human prostate carcinoma are some of the cell lines that 145) [25].
Plagiochila contains hundreds of species there have been no previous pharmacological or phytochemical findings on this species to our knowledge.
is a South American plant whose extract is the subject of two patents, one of which refers to its application in the treatment of skin and phaneres. The other concerning its potential as a source of anticancer or anti-inflammatory medicines [26]. Pharmacological screening of the ethanol extracts and fractions of two Peruvian medicinal plants, disticha and Ambrosia peruviana the isolation and characterization of three ent-2,3-secoaromadendrane-type sesquiterpenoid, plagiochiline, as well as two pseudoguaianolides, damsin(4) and confertin (5)

 Blumea balsamifera
It's a wild terrestrial plant that may reach altitudes of 2200-3500 metres in wet to dry climates. It goes by a variety of names in different nations, including Ainaxiang and Dafeng China. Local names in Indonesia include sembung gantung, Langu (Java), Kamadhin (Madura), Capo (Sumatra), and Madikapu (Madikapu) (Eastern Indonesia) [44]. Because of its high essential oil concentration, it is often used as incense. In Thailand, the dried leaves of this plant may be used as a cigarette to treat sinusitis, colic pain, and cough, and can also be combined with other plants as a bath component for new mothers [45]. People in the Philippines are more familiar with the term Sembung, a traditional medication used to treat kidney stones, the common cold, and as a diuretic [46]. Sembung is also used as an Ayurvedic medicine in other Asian nations, such as Malaysia and India [47].

 Blumea lacera
India, China, Malaya, and tropical Africa are the most common locations of this plant [48]. Kukusunga is the native name for an herbaceous weed. The herb has been used as an anthelmintic, astringent, diuretic, and antibacterial for thousands of years [49]. It is said to be effective in the treatment of bronchitis and blood disorders. The antileukemic activity of a hot extract of B. lacera against anti-K562, L1210, and U937 leukaemia cells has been observed [50]. Raushanara Aktar described the isolation and characterization of a novel steroidal glycoalkaloid as well as the identification, characterization, and cytotoxic action of this plant. Its cytotoxic activity, apoptotic potential, and cell cycle impact are all being assessed [51].

 Blumea eriantha
It's a tiny annual plant that grows up to 1 ml in height and has a camphor-like odour. It's often found in tropical areas, and the juice is used as a carminative. Antibacterial, antifungal, and insecticidal activities are found in the essential oil taken from the leaves and stem [52]. Traditionally, this herb has been used as a diuretic and to cure Cholera [53]. MTT assays on HeLa and B16F10 cell lines were used to assess the cytotoxic and antiproliferative properties of B. eriantha methanolic extract of leaves in vitro [54].

 Calendula officinalis
It's sold throughout Central and Southern Europe, Western Asia, and the United States of America [55]. Pot marigold is the English name, while Zergul is the Hindi name [56,57]. It's a biennial or annually flowering plant. The flowers and leaves are the main therapeutic components of the plant. Flowers were also utilized medicinally for their essential oil, which grew to be 30-60 cm tall. 10-20 cm ling, lower spatulate leaves Flower heads yellow to orange, corolla oblong spatulate, and stem angular, hairy, and solid. Saponins and triterpenes, for example, were among the chemical components. Antibacterial, antifungal, anthelmintic, antiviral, antioxidant, and hepatoprotective are some of the therapeutic benefits [58].

 Tagetes erecta
It is a beautiful plant that is frequently used to treat bronchitis, rheumatoid arthritis, colds, and respiratory illness, as well as a stimulant and muscle relaxant. In the Amazonia area, the essential oil of T. erecta leaves has schistosomicidal effects and is used as an anthelminthic. The essential oils of Tagetes erecta were tested for their cytotoxicity action. It was tested on tumour cell lines such as human colon carcinoma (HT29), human breast adenocarcinoma (MCF-7), human cervical adenocarcinoma (HeLa), and human hepatocellular liver cancer (HepG2). The cytotoxic activity was evaluated using the XTT assay [59].

CONSENT
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ETHICAL APPROVAL
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COMPETING INTERESTS
Authors have declared that no competing interests exist.