Analysis of Some Phytochemicals as Potential Anticancer Agents Targeting the Receptor Protein Associated With Cancer


 Cancerous growth is characterized as the uncontrolled multiplication and spread of the body's particular cells causing infection and addresses one of the greatest medical care issues for humanity and requests a proactive procedure for fix. Sensitization of cancer cells to conventional drugs using multi-target agents that block survival and oncogenic pathways, alone or in combination, is an emerging strategy to overcome drug resistance. Plants are natural reservoirs of novel compounds and provide a promising therapeutic approach for treatment of cancer. Phytochemicals are viewed as appropriate possibility for anticancer medication advancements due to their pleiotropic activities on track occasions with numerous habits. These phytochemicals frequently act by means of regulating molecular pathways which are embroiled in development and dissemination of cancer. The particular strategies in cancer prevention involves tracking of anti-carcinogenic agents, carcinogen inactivation, repressing proliferation, induction of cell cycle capture and apoptosis; and regulating the immune system. Presently, research is in progress for search of novel phytochemicals having anti cancerous properties with minimum or zero side effects. Numerous phytochemicals and their determined analogs have been recognized as possible contender for anticancer treatment and the present review article sheds light on few of these phytocompounds.


Introduction
Cancer is characterized as the uncontrolled multiplication and spread of the body's particular cells. Cell division is a simple cycle from the earliest starting point of life in the universe. Symmetric cell division prompts multiplication and asymmetric cell division is an enlightening advance for differentiation. It has been accounted that unusual symmetric cell division is the central point for causing cancerous growth. These phytochemicals have been tried against cancer viability at both in vitro and in vivo levels. They have complementary mechanisms to hinder the carcinogenic process by searching free radicals, inhibiting survival and multiplication of malignant cells, as well as reducing invasiveness and angiogenesis of tumors. They present wide and complex scope of activities on various molecular targets and signal transduction pathways including receptors, kinases, downstream tumor-activator or suppressor proteins, transcriptional factors, microRNAs (miRNAs), cyclins, and caspases (Choudhary et al., 2020).

Currently Available Drugs For Cancer Treatment And Their Limitations
Cancer treatment includes physical removal of tumor, radiotherapy and chemotherapy. Treatment strategy relies on the stage and location of tumor. Chemotherapy includes cytotoxic and cytostatic medications and end up being extremely e cient when utilized in blend with different treatments. Legitimate chemotherapeutics include alkylating molecules, topoisomerase inhibitors, tubulin acting agents and antimetabolites. Alkylating agents bind covalently with DNA, crosslink them and produce strand breaks. Carboplatin, cisplatin, oxaliplatin, cyclophosphamide, and melphalan are model alkylating agents which work by causing such damage to DNA. Doxorubicin and irinotecan are topoisomerase inhibitors and block DNA replication. Tubulin acting agents hinder mitotic spindles and arrest mitosis. Paclitaxel, docetaxel, vinblastine and vincristine follow up on tubulins. Paclitaxel (C47H51NO14) has been demonstrated as a potent anticancer medication against the vast majority of the cancer types. It was extracted in 1967 from the endophytic fungi found in Taxus brevifolia bark (Carsuso et al., 2000). Paclitaxel targets tubulin and blocks microtubules separation from the centrosomes. The previously mentioned drugs are acceptionally successful against a wide range of cancer, however these medications also have some limitation, during the course of treatment and healthy cells are also targeted and get destroyed like cancerous cells. Sometimes adverse effects of chemotherapy or radiation can lead to drastic changes in the internal cellular environment which might lead to death. There are cells in our body which increase rapidly in number under typical physiological conditions like hair follicle cells, bone marrow cells and digestive tract cells and so forth. The present anticancer medications focus on quick isolation of ordinary cells which is a major challenge, subsequently; give rise to adverse side effects.
Because of these results there is decrease in blood formation, GIT aggravation, balding, immunosuppression, heart illnesses and nerve problems may emerge. Another limit is that these cancer cells resist these medications as they go through changes. For instances Drug resistant genes (ABCA4 and ABCA12) were found to be over expressed in human MCF-7 breast cancer cells when docetaxel was applied. In another case, when phytochemical curcumin was applied with docetaxel down regulation of the drug resistant genes (Aung et al., 2017) is observed. Consequently, treating diseased cells by utilizing mono-target chemical agent is certainly not an effective method. In view of wide discoveries, phytochemicals and their analogs have most promising choice for better and less toxic cancer treatment (Singh et al., 2016). One of the major impediments in modern chemotherapeutics is multidrug resistance (MDR). The mutation or gene malfunctioning ought to probably result in MDR. Recurrence of chemotherapy can also additionally result in MDR and reduce e ux chemotherapeutic agent outside cell or antiapoptotic mechanism. The MDR proteins reduce the drug e cacy in selected tumor types, showing variable drug penetration rate.
The alternative therapeutic approach became identity of biomarkers earlier than or throughout therapy. The biosensing or diagnostics is an emerging science dealing with identity of biomarkers for MDR tumor types. But time and cost concerned in development are very high (Robey et al, 2018).
The conventional combination therapy wasn't suitable for all malignant MDR tumors either. The conventional therapy did not have selectivity or target ability and fails to provide most appropriate healing response. The selectivity towards most cancers cell is that the major drawback of conventional cancer therapy (Khatoon et al, 2020). Free doxorubicin (DOX, one of the most widely used chemotherapeutic agents for the treatment of cancer) generally has a high resistance factor (RF) value, which is considered to be a signi cant value.To solve this problem, a kind of silicon nanowire (SiNW)based drug nanocarrier (SiNWDOX) that exhibits high e ciency in the treatment of drug-resistant cancer cells is being reviewed. In general, drug-resistant cancer cells (such as MCF7/ADR cells) are greatly inhibited by SiNW-based nanocarriers, but it is also a very costly and time-consuming step (Peng et al, 2014).

Phytochemicals In Cancer Therapy
Plants and their bioactive mixtures are in therapeutic practices since long time. Several plant species and their phytochemical derivatives inhibit the development and progress of cancer cells (Aung et al., 2017). It has been explored that plant kingdom comprises roughly 250 000 plant species and just around 10% have been studied for treatment of various diseases. Phytochemicals and their analogues are found in various parts of the plant, e.g., owers, ower stigma, pericarp, sprouts, organic products, seeds, roots, rhizomes, stem, leaf, bark and play several pharmacological roles. A few plant items like alkaloids, avonoids, lignans, saponins, terpenes, taxanes, nutrients, minerals, glycosides, gums, oils, biomolecules and other essential and optional metabolites assume critical parts in either repressing disease cell initiating proteins, catalysts and signaling pathways [Cdc2, CDK2 and CDK4 kinases, topoisomerase chemical, cycloxigenase and COX-2 (Cycloxigenase), Bcl-2, cytokines, PI3K, Akt, MAPK/ERK, MMP, TNK,mechanistic target of rapamycin (mTOR) (  Colchicine upregulates dual speci city phosphatase 1 (DUSP1) quality in gastric cancer. It also suppresses the development of hepatocellular carcinoma cells through upregulation of A-kinase anchoring protein 12(AKAP12) and transforming growth factor beta-2(TGF-b2) proteins (Kuo et al., 2015).

Molecular Targets And Mechanism Of Action Of Anticancer Phytochemicals
Podophyllotoxin blocks the development of MCF-7 breast cancer cells by modifying checkpoint kinase 2 (Chk-2) signaling pathway. Podophyllotoxin likewise advances apoptosis in lung carcinoma cells through ER stress, autophagy and cell cycle capture (Choi et al., 2012).
Oroxylin A may be a conceivable iso avone extracted from Scutellariae radix that down-regulates COX2 and iNOS gene expression, blocks NFkB, and suppresses LPS-induced NFkB activation. Oroxylin A with 5-FU is additionally accustomed treat colorectal cancers, showing twofold activity with COX-2 reduction and expanded ROS production (Iqbal et al., 2017).
Taxanes show promising anticancer properties that act by binding to microtubules and has key part in cellular division. Paclitaxel (taxol) was rst removed from the bark and leaf of Taxus baccata and T. canadensis, Corylus avellana and is used to mend a large scope of cancer growths including ovarian, breast and therefore the lungs. Binding of paclitaxel with β-tubulin within the lumen of microtubules prompts decline in microtubule dynamics and stop cell cycle at M stage while docetaxel, a semi synthetic subsidiary from T. baccata is basically utilized in breast, pancreas, prostate and lung cancer treatments. (Iqbal et al., 2017) Resveratrol is a naturally occurring polyphenol and has been distinguished in mulberries, peanuts, grapes, bilberries and blueberries. Resveratrol plays important part in relieving a large scope of cancer including breast, colorectal, liver, pancreatic, prostate and lung carcinoma by up-regulating p53 and Bcl-2 related X proteins and down-regulating NF-kB, MMPs, Bcl-2, A P-1, cyclins, cyclin dependent kinases, cytokines, and COX-2 proteins. Resveratrol is thought to hinder angiogenesis, suppressing VEGF protein activity by decreasing MAP kinase phosphorylation (Patel et al., 2010).

Future Perspectives And Concluding Remarks
It has been observed that phytochemicals ll in as promising and compelling exploration region with splendid future in cancer treatment.

Competing Interest
No con ict of interest among the authors.

Author Contributions
All authors contributed to the study conception and design. The idea and topic were suggested by Dr.Subarna Ghosh. Literature search and data review were performed by Anindita Datta and the manuscript was critically revised and put together by Rishabh Sen. All authors read and approved the nal manuscript.

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