NTCC PPT.pptx

anticancer phytoconstituents

1. PHYTOCONSTITUENTS AND THEIR CHEMOPREVENTIVE ROLE IN BREAST CANCER Student name: Nandita Rajoteaya Programme: M.Pharmacy (Pharmaceutical chemistry) Enrollment No. : A1065522003 Name of Faculty Guide: Dr. Ramanpreet Walia AMITY INSTITUTE OF PHARMACY, NOIDA AMITY UNIVERSITY, SECTOR-125 NOIDA (UTTAR PRADESH) INDIA 2022-2024 1

2. ABSTRACT Breast cancer is a severe health problem majorly in females worldwide and is the leading cause of death in the world nowadays. Treatments provided such as chemotherapies, radiation therapies, hormonal therapies, and more targeted approaches like inhibition of aromatase or anti- estrogen drugs, inhibiting progesterone, etc. are still not effective and the patient is left with various side effects as well. Resistance, relapse, and metastasis are still common and are the leading cause of mortality in breast cancer patients. Researchers have gained knowledge of molecular mechanisms underlying cancer progression, which led to the synthesis of many anticancer drugs. Traditional medicines have shown remarkable and promising effects in the treatment of cancer as well as improving the efficiency of certain anticancer drugs. Traditional medicines included phytoconstituents and their derivatives which are used along with chemically synthesized drugs or independently for curing certain diseases. Moreover, phytoconstituents and their derivatives show synergism against breast cancer when integrated with any kind of therapy. This article primarily focuses on the ongoing research and clinical and preclinical studies of some of the most potent phytoconstituents used in breast cancer treatment. Phytoconstituents and their derivatives from terpenoids , alkaloids, steroids, polyphenols, glycosides, and quinones that help in the treatment of breast cancer and their mechanism of action such as inhibiting proliferation, cell cycle arrest, carcinogen inactivation, and apoptosis are included in this presentation. 2

3. TABLE OF CONTENT S. No. TITLE 1. Introduction 2. Goals of cancer treatment 3. Molecular profile classification of breast cancer 4. Gene mutations in breast cancer 5. Where breast cancer starts? 6. Development of cancer and Phytochemical Pathway Actions 7. List of Phytoconstituents as therapeutics 8. Conclusion 3

4. INTRODUCTION Breast cancer is the second leading cause of cancer deaths in women in 2016 with 246,660 new cases and 40,450 deaths in the United States. A total of 4 stages of cancer are there. The earliest cancers are assigned stage 0 (intraepithelial carcinoma) and are stages I through IV. The most aggressive is stage 4 of the disease. A higher stage means more advanced metastatic cancer. Some stages are further divided into sub-stages A, B, and C. If detected early ( eg stage 1, focal breast cancer), the 5-year survival rate is 100%. Cancer usually spreads to other organs. Breast cancer usually spreads to the lungs, bones, liver, or brain. 4

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7. MOLECULAR PROFILE CLASSIFICATION OF BREAST CANCER Hormone receptor positive [ estrogen receptor-positive] Hormone receptor-positive is a subtype of breast cancer in which ER is expressed. Human epidermal growth factor receptor (EGFR) 2 (HER2)-positive HER2-positive is a subtype of breast cancer that includes HER2, a member of the EGFR family. Triple-negative tumors Triple-negative breast cancer is a subtype of breast cancer that lacks three typical receptors, specifically ER, progesterone receptor (PR), and HER2. 7

8. GENE MUTATIONS IN BREAST CANCER Proto-oncogenes, which are found in normal cells, assist regulate when the cells grow, divide to generate new cells or stay alive. A proto-oncogene can develop into an oncogene by undergoing specific mutations. These mutant oncogenes can cause cancer in cells. Additionally, tumour suppressor genes exist in normal cells, which help regulate the frequency of cell division, the ability to correct DNA errors, and the timing of cell death. A cell can develop into cancer if a tumour suppressor gene has been altered. Gene mutation can be a result of: Inherited gene mutation Acquired gene changes 8

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10. WHERE BREAST CANCER STARTS? 10 Ducts : transportation of milk from lobules to nipples (ductal malignancies) Lobules : produce milk (lobular malignancies) Nipples : The ducts that join together and expand to form bigger ducts at the nipple of the breast allow milk to flow out of the breast . (Paget’s disease) Stroma : fat and connective tissue that surround lobules and ducts and maintain their position. ( phyllodes tumour) Lymphatic and blood arteries: provides blood flow to the breast (angiosarcoma) Tissues other than breast : sarcomas and lymphomas develop and are typically considered as breast cancer only

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12. DEVELOPMENT OF CANCER AND PHYTOCHEMICAL PATHWAY Carcinogenesis is a multi-step process with three primary phases: origin, promotion, and progression. A carcinogen often undergoes detoxification once it enters the body. It could, however, be triggered by several metabolic pathways. Carcinogenic substances cause oxidative stress, damage DNA, and start carcinogenesis. During the promotion phase, started cells begin to proliferate, resulting in preneoplastic cell buildup . The third and final phase, known as the advancement phase, is when these preneoplastic cells start to invade and spread throughout the body. The progression phase cannot be stopped and is irreversible. 12

13. Chemo-preventive drugs are often divided into two main groups both of which are mostly derived from plant phytochemicals. 1. BLOCKING AGENTS Prevent carcinogenic agents from interacting with the biomolecule and decrease carcinogen activation along the metabolic pathway . 2. SUPPRESSIVE AGENTS suppressive chemicals operate differently and stop the growth or spread of malignant cells . The majority of the time, chemo-preventive drugs control certain enzyme activities and cell cycles or have an anti-proliferative and anti-oxidant impact. These substances also control signal transduction pathways and stop the development of cancer. 13

14. LIST OF PHYTOCONSTITUENTS AS THERAPEUTICS IN BREAST CANCER TREATMENT S.No . PHYTOCHEMICAL MAJOR SOURCE FAMILY PHYTOCONSTITUENT CATEGORY 1. 10-gingeral Zingiber officinale Zingiberaceae beta- hydroxy ketone (phenol) 2. Actein Actaea racemosa Ranunculaceae Triterpenoid 3. Allicin Allium sativum L. Amaryllidaceae Alkaloid 4. Artemisinin Artemisia annua Asteraceae Sesquiterpene alkaloid 5. Asiatic acid Centella Asiatica Umbelliferae Pentacyclic triterpenoid 6. Berberine Berberis sp. Berberidaceae Benzyl-tetra isoquinoline alkaloid 7. Biochanin A Trifolium pratense Fabaceae Isoflavone 8. Cabazitaxel Taxus baccata Taxaceae Taxane 9. Calcaelin Calvatia caelata Agaricaceae - 10. Cannabinoid Cannabis sativa Cannabaceae - 14

15. 11. Chicoric acid Echinacea angestifolia Asteraceae phenylpropanoid 12. Curcumin Curcuma longa Zingiberaceae Phytopolyphenol 13. Daidzein Glycine max Fabaceae Isoflavones 14. Emodin Rheum rhabarbarum Polygonaceae Anthraquinone 15. Epigallocatechin gallate Camellia sinensis Theaceae Phenolic antioxidant 16. Etoposide Mandragora officinarum Solanaceae Alkaloid 17. Genistein Glycine max Fabaceae Polyphenolic isoflavones 18. Gossypol Gossypium hirsutum Malvaceae Phenolic aldehyde 19. Harmine Peganum harmala Nitrariaceae beta-carboline and a harmala alkaloid 20. Ipriflavone Derived from daidzein Fabaceae Isoflavone 21. Kaempferol galactoside Bauhinia variegata Leguminosae Flavonol glucoside 22. Lappaol F Arctium lappa Asteraceae 2-arylbenzofuran flavonoids 15

16. 23. Larotaxel Taxus baccata Taxaceae Taxane 24. Lycopene Solanum lycopersicum Solanaceae Tetra triterpene 25. Nab-paclitaxel Taxus brevifolia Taxaceae Taxane 26. Paclitaxel Taxus brevifolia Taxaceae Taxane 27. Plumbagin Plumbago zeylanica Plumbaginaceae Toxin and dye 28. Podophyllotoxin Podophyllum peltatum Podophyllum emodi Berberidaceae Podophyllotoxin 29. Pomiferin Maclura pomifera; Dereeis Malaccensis Moraceae Isoflavonoid 30. Quercetin Nasturtium officianale Brassicaceae Flavonoid 31. Resveratrol Polygonum cuspidatum Polygonaceae Stilbenoid (polyphenolic phytoalexin) 32. Solamargine Solanum nigrum Solanaceae Glycoalkaloid 33. Shikonin Lithospermum erythrorhizon Boraginaceae Naphthoquinone 16

17.   34. Sulforaphane Brassica oleracea Brassicaceae Dietary isothiocyanate   35. Thymoquinone Nigella sativa Ranunculaceaen Essential oil   36. Tylophorin Tylophora indica Apocynaceae Phenanthraindolizidine alkaloid   37. Vindesin Catharanthus roseus Apocynaceae Vinca alkaloid   38. Vinorelbine Catharanthus roseus Apocynaceae Vinca alkaloid   39. Vitexin Vitex Agnus-castu Lamiaceae Apigenin flavone glycoside   40. Wedelolactone Eclipta alba Asteraceae Polyphenol   41. Withaferin A Withania somnifera Solanaceae Phytosterol   42. Withanolide D Withania somnifera Solanaceae Phytosterol 17

18. CONCLUSION Cancer chemoprevention using herbal compounds has become a preferred approach in cancer treatment. The study of new chemopreventive plant compounds has become a central goal of cancer research and also helps in the search for new therapeutic targets . Chemopreventive agents enhance the efficacy of chemotherapy and radiotherapy through multiple signaling pathways. As oxidative stress plays an important role in the pathogenesis of many cancers, the antioxidant effects of dietary phenolic compounds may represent a promising strategy for cancer prevention. Dietary antioxidant phytochemicals are abundant in plants and represent diverse classes of compounds that exert diverse mechanisms of action against tumors . Therefore, chemoprevention with a diet rich in plant-based antioxidants shows great potential to reduce risk factors associated with cancer progression. 18

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