0Tashkent Medical Academy Integration of Science, Education and Practice in Modern Psychology,
Pedagogy: a Problem and Solutions
Toshkent tibbiyot akademiyasi Zamonaviy psixologiya, pedagogikada fan, ta'lim va amaliyot integratsiyasi:
muammo va yechimlar
THERAPEUTIC POTENTIAL OF TRADITIONAL MEDICINAL PLANTS
ON BREAST CANCER
Ranjit Kumar, Bendang AO and Pranay Punj Pankaj
Department of Zoology, Nagaland University, Lumami Nagaland - 798627, India.
Email: ranjitzool17@gmail.com
ABSTRACT
Globally breast cancer is a disease which severely effects the human population. It is leading cause of death in female worldwide. The disease is characterized by cells in the human body continually multiplying with the inability to be controlled or stopped. Consequently, forming tumors of malignant cells with the potential to be metastatic. Current treatments include chemotherapy, radiotherapy and chemically derived drugs. Treatments such as chemotherapy can put patients under a lot of strain and further damage their health. Therefore, there is a focus on using alternative treatments and therapies against cancer. Scientific and research interest is drawing its attention towards naturally-derived compounds as they are considered to have less toxic side effects compared to current treatments such as chemotherapy. The Plant Kingdom produces naturally occurring secondary metabolites which are being investigated for their anticancer activities leading to the development of new clinical drugs. Many plants acts on microtubule assembly, few acts on suppression of cell cycle and few activate tumor suppressor genes. Its combined effect may be used in development of new cancer therapy in future. It must reduce toxic effect of modern chemotherapeutic drugs as well as it economizes cancer treatment. These traditional medicines must be used for cancer treatment regimen for effective cancer therapy.
Keywords: Chemotherapy, radiotherapy, medicinal plants, therapy
INTRODUCTION
Breast cancer is one of the leading cancer responsible for very high number of mortality among women worldwide, still treatment outcomes are very poor due to diagnosis in late stage and it is major global public health issue. Treatment of breast cancer is easy if reported in early stage but if diagnosed in latter stage treatment outcomes is very poor. According to the most recent worldwide cancer burden estimates, 2.26 million cases of breast cancer are diagnosed [1] and 6,85 000 fatalities were reported worldwide in 2020[2].Out of36 cancers in 185 countries breast cancer
33
April 26, 2024
rank one in women; it has overhaul lung cancer as the most often diagnosed cancer in women [3]. Age standardized rate per 1, 00,000 population shows 47.8% incidence rate and 13.6% mortality rate worldwide. In India, incidence rate of breast cancer is 13.5%, mortality is 10.6% and five year prevalence rate is 69.28 thus breast cancer stand at rank 1 position among all other cancers in India. [2]. It is a cancer that begins in the cells of the breast and has the propensity to outspread to apart organs such the bone, liver, lung and brain [3]. Breast cancer can be classified into several categories, each of which develops when cancerous cells and tissues spread throughout the body. Non-invasive and invasive breast cancers are two broadly categorized types of breast cancer. Non invasive breast cancer cells are the cells that are restricted to the ducts and do not penetrate the breast's connective tissues and fatty tissues and have not migrated beyond the lymph nodes or to the breast tissues. Lobular carcinoma and Ductal carcinoma comes under the category of non-invasive breast cancer [4]. Invasive breast cancer occurs when aberrant cells from the milk ducts or lobules branch off into the close proximity to breast tissue [5]. Medullary carcinoma, adenocystic carcinoma, papillary carcinoma, Tubular carcinoma and Mucinous carcinoma are included in invasive breast cancer [5].
Molecular mechanism of breast cancer
There are numerous aspects which may acts as risk factors for breast cancer, out of which multiple genetic cascade balance is needed for maintaining normal breast homeostasis. Alteration in these genetic pathways is always associated with genomic anomalies which may lead to apoptosis or carcinogenesis. Heterogeneity caused by genomic instability is common in breast cancer and it includes chromosomal structural rearrangements, mutations, copy number changes, DNA replication, mitotic chromosomal segregation, transcription and telomere preservation are all involved in instability in genome. Breast cancer susceptibility genes have been discovered using a variety of methods and mutations in these genes confers the possibility of breast cancer [6]. Genes like BRCA1,BRCA2,p53 ,CHEK2,ATM,PALB2,RAD50,PARP2,CDH-1,Cyclin D, PTEN and BRIP1 accounts for the susceptibility. A single gene mutation may be corrected by genomic machinery or goes to oncogenic transformation; however, it does arise when mutations occur in critical genes that fall into three categories: DNA repair genes, tumour suppressor genes and proto-oncogenes (Figure - 1). The cell cycle is in charge of controlling cell growth and proliferation[7]. Several factors, including ageing, sex, hormone use, gene mutations, family history, alcohol consumption and an unhealthy lifestyle might elevate the probability of getting breast cancer[8].
34
April 26, 2024
Figure 1- Showing gene cascade leading to breast cancer. It may involve cell cycle genes and different pathways of apoptosis. Genes such as BAD, PUMA, NOXA, PTEN, C-MYC are responsible for apoptosis and it's irregular expression. CDK1, CDK2, CDK4 ,CDK6 and Cyclins play important role in regulating cell cycle its alteration may lead to breast cancer. Cancer cells proliferation is frequently associated with alterations in Cell cycle checkpoints mainly CDK's and cyclins imbalances.
Medicinal Plants for cancer therapy
Plant-derived drugs are desired for anticancer treatment as they are natural and readily available. They can be readily administered orally as part of patient's dietary intake. Since it was naturally derived compounds from plants, it showed more tolerence and non-toxic to normal human cells. However, there are exceptions such as cyanogenetic glycosides, lectins, saponins, lignans, lectins and some taxanes. If plant-derived drugs can demonstrate selectivity in research, are non-toxic to normal cell lines and show cytotoxicity in cancer cell lines, these drugs can lead to clinical trials for future. Herbal medicines are still used in developing countries as the primary source of medical treatment for many years. Plants have been used in medicine for their natural antiseptic properties [9]. Thus, researches are required to investigate the potential properties and uses of terrestrial plants extracts for the preparation of potential nanomaterial based drugs for diseases including cancer. Many plant species are already being used to treat or prevent cancer development. Multiple researchers have identified species of plants that have demonstrated
35
April 26, 2024
anticancer properties with a lot of focus on those that have been used in herbal medicine in developing countries.
Compounds which are characteristic to the plant kingdom are necessary for plant survival and "housekeeping" of the organism. These plants being investigated for their ability to inhibit growth and initiate apoptosis in cancerous cells. Medicinal plants have been used for thousands of years in folk medicines in Asian and African populations and many plants are consumed for their health benefits in developed nations. According to the World Health Organisation (WHO) some nations still reply of plant-based treatment as their main source of medicine and developing nations are utilizing the benefits of naturally sourced compounds for therapeutic purposes[10]. Compounds which have been identified and extracted from terrestrial plants for their anticancer properties include polyphenols, brassinosteroids and taxols.
Polyphenolic compounds include flavonoids, tannins, curcumin, resveratrol and gallacatechins are all considered to be anticancer compounds. Resveratrol can be found in foods including peanuts and grapes and red wine. Polyphenols are thought to have apoptosis inducing properties showing anticancer properties which can be utilized. The mechanism in which polyphenols are thought to carry out apoptosis initiation is through regulating the mobilization of copper ions which are bound to chromatin inducing DNA fragmentation. In the presence of Cu (II), resveratrol was seen to be capable of DNA degradation. Cancer agents may be altered through the polyphenol regulating acetylation, methylation or phosphorylation by direct bonding. For example, curcumin treated cancer cells in various cells lines have shown suppression of the Tumour Necrosis Factor (TNF) expression through interaction with various stimuli. polyphenols can inhibit or alter the regulation of proteins and other agents which may be contributing to the survival of cancer cells[11].
Flavonoids are the polyphenolic compounds and constitute a large family of plant secondary metabolites with 10,000 known structures. They are physiologically active agents in plants and becoming of high interest scientifically for their health benefits [12]. Flavonoid shows cytotoxicity on cancer cells and to have high free radical scavenging activity. Purified flavonoids have also shown anticancer activities against other human cancers including; hepatoma (Hep-G2), cervical carcinoma (Hela) and breast cancer (MCF-7) [13].
Brassinosteroids (BRs) are naturally occurring compounds found in plants which play roles in hormone signalling to regulate growth and differentiation of cells, elongation of stem and root cells and other roles such as resistance and tolerance against disease and stress [14]. BRs are used for regulation of plant senescence. They
36
April 26, 2024
are essential for plant growth and development. BRs are other naturally occurring compounds which have demonstrated therapeutic significance against cancer. A characteristic of cancer cells is that they do not naturally undergo apoptosis and proliferate indefinitely[15]. BRs can induce responses necessary for growth inhibition and induce apoptosis by interacting with the cell cycle. BRs have been used in investigations to treat a range of cancer cell lines which include; T-lymphoblastic leukaemia CEM, multiple myeloma RPMI 8226, cervical carcinoma HeLa, lung carcinoma A-549 and osteosarcoma HOS cell lines
CONCLUSION
Deregulations in apoptosis and cell cycle progression, gain in the expressions of oncogenes and loss of expression in tumor suppressor genes leads to high susceptibility of breast cancer. Genes such as c-myc, p53, BAD, PUMA, NOXA, c-fos, PTEN leads to apoptotic pathway, in case of loss of these genes or any deregulation leads to breast cancer. CDK1, CDK2, CDK4, CDK6 and Cyclin play important role in synchronizing cell cycle. Cancer cells proliferation is frequently associated with alterations in Cell cycle checkpoints like CDK's and Cyclin. Few plant extracts has tendency to bind the tubulin subunit of microtubules and stabilizes the microtubule to normal assembly play key role in cancer therapy. Few plant extract has ability to control cell divisions must be useful for cancer treatment. Discovery of anticancer cancer agents which show specificity towards breast cancer cells and can induce cell death and inhibit growth of tumors may be considered for clinical trials in future for cancer treatment. Many plants possesses high antioxidant property are used for cancer therapy. The drug developed through medicinal plants does not show any deleterious health impact on non targeted cells as well as it would be very economical for breast cancer patients. Acknowledgement
Authors are thankful to Nagaland University for providing all support during this research work.
REFERENCES:
1.M. Akram, M. Iqbal, M. Daniyal, and A. U. Khan, (2017)"Awareness and current knowledge of breast cancer," Biol. Res., vol. 50, no. 1, pp. 1-23, doi: 0.1186/s40659-
017-0140-9.
2. S. Asia, S. Asia, and H. Hdi,(2020) "Source: Globocan 2020," vol. 419, pp. 1-2,.
3. Y. S. Sun et al.,( 2017)"Risk factors and preventions of breast cancer," Int. J. Biol.
37
April 26, 2024
Sci., vol. 13, no. 11, pp. 1387-1397, doi: 10.7150/ijbs.21635.
4. G. N. Sharma, R. Dave, J. Sanadya, P. Sharma, and K.K.Sharma, (2010)"March 2010 Revised: 19," J. Adv. Pharm. Technol. Res., vol. 1, no. 2, pp. 109-126.
5. Y. Feng et al.(2018) "Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis," Genes Dis., vol. 5, no. 2, pp. 77-106, doi: 10.1016/j.gendis.2018.05.001.
6.C. Wendt and S. Margolin, (2019)"Identifying breast cancer susceptibility genes-a review of the genetic background in familial breast cancer," Acta Oncol. (Madr)., vol. 58, no. 2, pp. 135-146, doi: 10.1080/0284186X.2018.1529428.
7.B. S. Meligy, S. Kamal, and S. A. El Sherbim,(2016) "Electronic Physician ( ISSN : 2008-5842 )," Electron. Physician, vol. 8, no. 10, pp. 3057-3061.
8. S. E. Singletary,(2003)"Rating the Risk Factors for Breast Cancer," vol. 237, no. 4, pp. 474-482.
9.Taneja SC, Qazi GN. In: Bioactive Molecues in Medicinal Plants: A perspective in their therapeutic action, in Drug discovery and development. Chorghade MS, editor. John Wiley and Sons, Inc; 2007. pp. 1-50
10. A.L. Parker, M. Kavallaris, J.A. McCarroll, Microtubules and their role in cellular stress in cancer Frontiers in Oncology, 4 (2014), p. 153
11. B. Guerra, O.G. Issinger, Natural Compounds and Derivatives as Ser/Thr Protein Kinase Modulators and Inhibitors Pharmaceuticals (Basel, Switzerland), 12 (1) (2019), p. 4
12.. Ngamkitidechakul, K. Jaijoy, P. Hansakul, N. Soonthornchareonnon, S. Sireerata wong Antitumour effects of Phyllanthus emblica L.: Induction of cancer cell apoptosis and inhibition of in vivo tumour promotion and in vitro invasion of human cancer cells Phytotherapy Research, 24 (2010), pp. 1405-1413
13. T. Pooja, Plants with Anticancer properties: A Review on traditional plants and herbs are used to evaluation for their anticancer potential, Journal of Pharmacy Research, 11 (s) (2017), pp. 547-553
14.G. Antonio and T. Giuseppina, Curcumin and Cancer, Nutrients, 11 (2376) (2019), pp. 2-19,
15. A.A.N. Rumana, M.A.K. Srivastava, Evaluation of in vitro anticancer activity of stem of Tinospora cordifolia against human breast cancer and Vero cell lines, Journal of Medicinal Plants Studies, 3 (4) (2015), pp. 33-37
38
April 26, 2024
