A phytomolecule can inhibit the development of pre- neoplastic cell carcinomas, and interfere with the metabolic transformation of pro-carcinogen. Likewise, they can regulate cell and signaling events engaged with development, invasion and metastasis of cancer cell.
Flavanones, isoflavones and lignans restrict the estrogen to the cancer cells and reduce their multiplication. Decrease of inflammation processes through concealment of nuclear factor-kappa B (NF-kB) family transcription factors is a separate mechanism. Curcumin, bilberries anthocyanins, EGCG, caffeic
acid and derivatives and quercetin act through NF-kB signalling pathway.
Luteolin hinders epithelial mesenchymal transition. Other than these mechanisms, anticancer phytomolecules focuses on a few other signalling molecules or pathways additionally to diminish the development and metastasis of cancer cells (Iqbal et al., 2017).
Apigenin, a flavone contained in parsley, celery and chamomile, promotes the apoptosis of lung adenocarcinoma cells by targeting the leptin/leptin receptor pathway. It induces caspase-dependent extrinsic apoptosis in human epidermal growth factor receptor 2 (HER2) through the expression of BT474 breast cancer cells by restriction of the signal transducer and stimulant. STAT3 (Seo et al., 2015). It was revealed that apigenin inhibits the PI3K / AKT / mTOR pathway and induces apoptosis and autophagy in hepatic carcinoma cells (Yang et al, 2018).
Curcumin, the polyphenol of Curcuma longa hinders the development of human glioblastoma cells by modulating several molecular segments. It up regulates p21, p16, p53, early growth response protein 1 (Egr-1), extracellular signal regulated kinase (Erk), c-Jun-N-terminal kinase (JNK), ElK-1, Bcl-2 associated X protein (Bax) and Caspase-3, 8, 9 proteins; and down regulates the degrees of B-cell lymphoma 2 (Bcl-2), mechanistic target of rapamycin (mTOR), p65, B-cell lymphoma extra-enormous protein (Bcl-xL), protein kinase B(Akt), epidermal growth factor receptor (EGFR), NF-kB, cell division cycle protein 2 (cdc-2), retinoblastoma protein (pRB), cyclin-D1 proteins and cell myelocytomatosis oncogenes(c-myc) (Vallianou et al., 2015).
Crocetin, the carotenoid present in Crocus sativus and Gardenia jasminoides follow up on GATA binding protein 4 and MEK-ERK1/2 pathway and prevents cardiac hypertrophy.
Cyanidin glycosides from red berries execute antioxidants and anticancer capacities through different process. In colon cancer cells, they smother the statements of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) genes and hinder mitogen induced metabolic pathways (Cai et al., 2009; Serra et al., 2013).
EGCG, the catechin polyphenol of tea shows anticancer effects through different mechanisms. It blocks NF-kB initiation, Bcl-2 and COX-2 expresion in prostate carcinoma cells and induces apoptosis. In bladder and lung carcinoma cells, it restrains matrix metallopeptidase-9 (MMP-9) expression. In head and neck carcinoma cells it suppresses the development of vascular endothelial development factor (VEGF). In fibrosarcoma cells it suppresses the Erk phosphorylation and action of MMP-2 and 9. Furthermore, in gastric carcinoma cells it blocks the Erk, JNK, and MMP-9 expression (Singh et al., 2011).
Fisetin and hesperetin cause cell cycle capture in human acute promyelocytic leukemia HL-60 cells by modifying a few signaling pathways, viz. mitogen initiated protein kinases (MAPK), NF-kB, JAK/STAT, PI3K/Akt, Wnt, and mTOR pathways. It shows double inhibition of PI3K/Akt signaling pathways in the lungs cancer (Adan et al., 2015).
Genistein, the isoflavone of soybean shows its anticancer impacts through inhibition of NF-kB and Akt signaling pathways and Gingerol focuses on the Erk1/2/JNK/AP-1 signaling and promotes caspase-dependent apoptosis in colon cancer (Radhakrishnan et al., 2014; Joo et al., 2016).
Lycopene targets the PI3K/Akt pathway in pancreatic cancer. It blocks gastric carcinogenesis by hindering Erk and Bcl-2 signaling. It initiates cell antioxidant enzymes (e.g., GST, GSH, and GPx) in the cancerous cells and eliminates oxidative malfunctions created by the carcinogens (Kim et al., 2015).
Rosmarinic acid decreases the activity of COX-2 and Erk phosphorylation in colon cancer cells. In breast cancer, rosmarinic acid lessens the action of DNA methyl transferase and interfere RANKL/RANK/OPG networks. Additionally, it targets PKA/CREB/MITF pathway and NF-kB enactment in melanoma and leukemia U938 cells (Hossan et al., 2014).
Calcitriol restrains prostaglandins, COX-2, NF-kB, and VEGF signalling and prevents angiogenesis of cancer cells. Tocotrienols and g-tocopherol prevent PI3K/Akt and Erk/MAPK pathways (Sylvester et al., 2013).
Colchicine upregulates dual specificity 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).
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 isoflavone 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 first 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).
Chrysin [5,7-dihydroxyflavone], is a successful anticancer compound showed less adverse effects and have solid antitumor consequences for various cancer growth cell lines (DU145 and PC-3). This flavone has also initiated apoptosis in SW480 colorectal disease, capture cell cycle at G2/M stage, brings about DNA cleavage and apoptosis, expanding ROS production and lipid peroxidation, suppresses the S6, AKT, PI3K, P90RSK and P70S6K, proteins, induces MAPK and ERK1/2 and P38 proteins within the prostate cancer cells (Iqbal, et al., 2017).
Chyricin induces prostate cancer cell death by inducing reactive oxygen species (ROS) and endoplasmic reticulum stress through inhibition of PI3K/AKT signaling (Ryu et al., 2017). Chrysin has also been shown to reinforce the sensitivity of tumour cells to doxorubicin by suppressing the cascade of PI3K/AKT (Issinger et al., 2021).
β-elemene a sesquiterpene, is moreover a promising anticancer expert with a large extent of its effect against drug resistant tumors and has been extracted from Curcuma wenyujin. β-elemene controls different kinds of cancer, advances apoptosis and cell death, hinder the expression of VEGF, downregulates Akt phosphorylation and CD34 suppression, hindering PI3K/Akt/mTOR, MAPK and pathway, tightening angiogenesis and upregulates the Cbl-b and c-Cbl and E3 ubiquitin ligases in human gastric cancer (Iqbal et al., 2017).
Thymoquinone (2-isopropyl-5-methyl-1, 4-benzo-quinone, TQ) is the strong constituent of black cumin (Nigella sativa) seed oil. In a BALB/c a thymic naked mice, thymoquinone decreased tumor weight and size by advancing apoptosis and subduing STAT3 phosphorylation in human gastric cancer cells. The downregulation of STAT3 activation in relationship with a decrease in JAK2 and c-Src activity. In another examination in BALB/c mice migrated with mouse epithelia breast cancer EMT6/P cell line, TQ and melatonin combination fundamentally reduced the tumor size, induced tumor cell death, lessened VEGF expression, and enacted anticancer immune response by extending INF-γ level (Zhao et al., 2016).
Ursolic acid (UA) is a natural terpene compound found in number of plants. The in vitro assessment suggested that treatment of CRC cells with UA and oxaliplatin essentially decreased cell duplication, extended apoptosis and ROS development, and prevented the expression of drug resistant gene (Zhang et al., 2018). The UA nanoparticles lessened tumor size by focusing on caspases and p53 with downregulation of Bcl-2 and cIAP, starting apoptosis and inciting cervical cancer cell demise (Wang et al., 2018).
These phytomolecules follow up on epigenetic components also. DNA methylation, histone modifications and miRNA expression are significant epigenetic measures which include in cancer growth initiation and growth. Phytomolecules decrease the functions and expressions of DNA methyl transferases (DNMTs), histone deacetylases (HDACs) and histone methyl transferases (HMTs) and increases promoter demethylation in different cancer models (Thakur et al., 2014).