A Review on Anti-Breast Cancer Activity of Selected Medicinal Plants

Asian Journal of Pharmaceutic s • Oct-Dec 2024 • 18 (4) | 1166 A Review on Anti-Breast Cancer Activity of Selected Medicinal Plants Harshitha Kancharla 1 , Prasanthi Samathoti 2 1 Department of Pharmaceutical Analysis, MB School of Pharmaceutical Sciences (Erstwhile Sree Vidyanikethan College of Pharmacy) Mohan Babu University, Tirupati, Andhra Pradesh, India, 2 Department of Pharmaceutics, MB School of Pharmaceutical Sciences (Erstwhile Sree Vidyanikethan College of Pharmacy), Mohan Babu University, Tirupati, Andhra Pradesh, India Abstract To review and identify medicinal plants and bioactive substances with potential anti-breast cancer activity and provide a complete overview for future research. A comprehensive analysis of all scientific studies, phytochemical screening, ethnobotanical surveys, plant medicinal applications, and anti-breast cancer activities of medicinal plants was conducted. These data were gathered by searching for relevant articles in databases such as PubMed, Scopus, Google Scholar, and Web of Science. Relevant studies included those published in peer-reviewed journals and reports from respective conservation agencies. The reviewed medicinal plants and their bioactive components demonstrated promising anti-breast cancer activities, including antiproliferative, apoptotic, anti-angiogenic, and antioxidant activities. This study emphasizes the potential of medicinal plants and their bioactive chemicals for the treatment of breast cancer. This is a significant resource for future research and the development of effective plantbased medicines. Herbal medications are promising alternatives to traditional chemotherapy, with fewer side effects and greater tolerability. Further research is required to fully understand the anti-breast cancer capabilities of these medicinal plants and their bioactive components Keywords: Breast cancer activity, breast cancer, medicinal plants, phytochemical constituents Address for correspondence: Dr. Prasanthi Samathoti, Department of Pharmaceutics, MB School of Pharmaceutical Sciences (Erstwhile SreeVidyanikethan College of Pharmacy), Mohan Babu University, Tirupati-517102, Andhra Pradesh, India. Phone: +91-09703372550/08329596247. E-mail: prasanthiram 84@gmail.com Received: 11-11-2024 Revised: 23-12-2024 Accepted: 31-12-2024 INTRODUCTION B reast cancer is a medical condition in which abnormal breast cells grow out of control and turn into tumors [1] In 2022, 2.3 million women received a diagnosis of breast cancer worldwide, accounting for 670,000 deaths from the disease [2] Breast cancer affects women globally, with 99% of cases occurring in women, whereas men only experience it in 0.5–1%. Factors such as aging, obesity, alcohol abuse, radiation exposure, family history, reproductive history, smoking, and post-menopausal hormone therapy increase the risk of breast cancer [3,4] Breast cancer symptoms include breast thickening or lumping, changes in breast size, shape, appearance, skin abnormalities such as dimpling, redness, pitting, or pitting, and alterations in the nipple or surrounding skin due to abnormal or bloody nipple fluid [5,6] According to the World Health Organization (WHO) estimates, in the absence of immediate action, the number of cancerrelated deaths will increase by almost 80% by 2030, with most of these fatalities taking place in countries with low and moderate incomes [7] Breast chemoprevention uses pharmaceuticals or natural substances to block the progression of pre-malignant cells with DNA damage, preventing the initiation of invasive breast cancer. However, due to severe side effects, it has not significantly reduced morbidity or death rates. As there is no viable treatment for advanced illnesses, the cancer is highly resistant to chemotherapy [8] The anti-tumor and anti-cancer effects of natural plant substances have shown promising results [9,10] The WHO recommends traditional medicines due to their effectiveness and safety, but some people still opt for herbal drugs for various reasons, such as health promotion, disease prevention, exhaustion of conventional therapies, dissatisfaction with efficacy, significant side REVIEW AR TICLE

Kancharla and Samathoti: Medicinal plants with anti-breast cancer potential Asian Journal of Pharmaceutic s • Oct-Dec 2024 • 18 (4) | 1167 effects, belief in herbal products, personal involvement in decision-making, and cultural or spiritual preferences [11] The National Cancer Institute has identified 3,000 medicinal herbs with consistent anticancer efficacy, based on their secondary metabolites, including isocatechins, catechins, lignans, coumarins, flavonoids, and flavones, from nearly 35,000 plant species [12] Hormonal issues often lead to cancer outcomes, which can be addressed by bioactive chemicals such as isoflavonoids and phytoestrogens. Plant flavonoids have been shown to have chemopreventive, estrogenic, and anti-estrogenic properties. Other medicinal compounds found in plants, such as taxol, camptothecin, vincristine, vinblastine, vinorelbine, vindesine, and vinflunine, have shown significant therapeutic value in various cancer treatments [13,14] Thus, this review aims to integrate information about medicinal herbs with anti-breast cancer activity. Figure 1 depicts a medicinal plant that contains various phytochemicals with anti-breast cancer activity. The phytochemicals present in various therapeutic plants that have anti-breast cancer properties are shown in Figure 2 DESCRIPTION OF MEDICINAL HERBS WITH ANTI-BREAST CANCER PROPERTIES Caesalpinia pulcherrima Barbados pride or peacock flower, or C. pulcherrima , is a herb used to treat menoxenia, pyrexia, wheezing, and bronchitis. Its effects include antiviral, purgative, emmenagogue, tonic, stimulant, and cathartic. Out of the herb’s 61 active ingredients, 29 have been linked to breast cancer. Gallic acid, catechin, rutin, elalic acid, quercetin, α -pinene, β -pinene, limonene, E-Verbenol, α -terpineol, α -copaene, and E-Caryophyllene are among the phytochemicals found in the flower that is used to cure breast cancer [15] C. pulcherrima is shown in Figure 3 Glycyrrhiza glabra Liquorice, or G. glabra , is a major species in the genus Glycyrrhiza that has medicinal qualities [16,17] The growth of MDA-MB-231 tumor cells is inhibited by its ethanolic root extract, contingent on dosage [18] The presence of triterpenoid saponin glycyrrhizin in the root extract is linked to its sweet flavor. The most abundant and primary phytochemical (10– 25%) in the root extract is glycyrrhizin [16] Strong antioxidant properties have been discovered in liquorice, which is abundant in phenolic compounds such as methylated isoflavones, chalcones, coumarins, and flavonoids [17,18] These substances are ascribed to the fruit’s extracted polysaccharides, chalcones, and saponins [19] These substances have promise for the development of novel anticancer drugs because they may possess strong antioxidant qualities that inhibit the growth of cancer. Glabridin, one of the flavonoids in licorice, can aid in the battle against cancer by starting the mitochondrial apoptotic pathway and caspase cascade, which kills cancer cells [20] G. glabra is shown in Figure 4 Securidaca longipedunculata The plant S. longipedunculata Fresen, also known as a violet tree in Northern Nigeria, is considered the mother of all remedies and is used by traditional medicine practitioners in African nations to treat various illnesses, including cancer [21] The phytochemical screening of S. longipedunculata root bark extract revealed flavonoids, cardiac glycosides, phenols, alkaloids, saponins, and reducing sugar as compounds with anti-oxidant and anti-cancer properties [22] S. longipedunculata is shown in Figure 5 Perilla frutescens A member of the Labiaceae family, P. frutescens is a perennial plant shown in Figure 6 . China, Korea, Japan, Vietnam, and other countries widely grow this popular traditional herb. It comes from the same origins as food and medicine [23] We can further classify it as a medicinal plant into Perilla plant material, Perilla leaves, and Perilla branches [23,24] P. frutescens contains various active compounds including tocopherols, phytosterols, fatty acids, terpenoids, [25] polyphenols, flavonoids, [26] anthocyanins, coumarins, carotenoids, neolignans, [27] glucosides, peptides, and related compounds. We used Perilla seed species for the triterpenoid camelliol C [28] Researchers found that additional pentacyclic triterpenes, such as ursolic acidic Figure 1: Types of phytochemicals from plants

Kancharla and Samathoti: Medicinal plants with anti-breast cancer potential Asian Journal of Pharmaceutic s • Oct-Dec 2024 • 18 (4) | 1168 Figure 2: Phytochemicals present in various plants with anti-breast cancer properties substances, oleanolic acid, corosolic acid, and marlinic acid, possess anti-tumor effects. Two common polyphenols, caffeic acid and Ros A, are antibacterial, [29] anxiety relievers, anti-depressive, liver-protective, [30] and have anticancer properties Catharanthus roseus C. roseus , another name for Vincarosea, shown in Figure 7 is an evergreen herb belonging to the Apocynaceae dogbane family. Since ancient times, it has been used to cure a wide Figure 3: Caesalpinia pulcherrima Figure 5: Securidaca longipedunculata Figure 4: Glycyrrhiza glabra Figure 6: Perilla frutescens

Kancharla and Samathoti: Medicinal plants with anti-breast cancer potential Asian Journal of Pharmaceutic s • Oct-Dec 2024 • 18 (4) | 1169 range of illnesses, such as rheumatism, diabetes, cancer, menstruation problems, dyspepsia, and indigestion. The plant possesses a broad range of pharmacological properties and is abundant in bioactive chemicals. It is frequently cultivated for its anticancer alkaloids, which include vincristine and vinblastine, two of the more than 130 varieties used to treat cancer. Amalicine, reserpine, and serpentine are among the 70 chemical compounds found in the plant’s leaves [31] Bauhinia variegata The flowering plant species B. variegata belongs to the Fabaceae family of legumes. We commonly refer to it as the orchid tree. The orchid tree possesses excellent anticancer and antioxidant properties. Researchers have examined its potential to prevent breast cancer [32] Numerous phytochemical compounds in B. variegata exhibit anticancer properties, particularly against breast cancer [33] Several compounds found in B. variegata have potent antitumor properties [34] These include three particular flavonoids that can stop the growth of cancer cells and trigger apoptosis: quercetin, kaempferol, and rutin [35] The plant B. variegata contains phytosterols, terpenoids, and phenolic acids that have been shown to be useful in promoting the death of cancer cells and lowering oxidative stress. Certain acids, such as gallic and ellagic acids, have been shown to be cytotoxic to cancer cells, resulting in cell death and halting growth [36] Terpenoids such as beta-sitosterol and phytosterols such as stigmasterol in B. variegata have been found to be cytotoxic to cancer cells, causing apoptosis and stopping cell proliferation [37] Furthermore, it has been demonstrated that the stem and root extracts inhibit the development of human breast cancer cells, with IC 50 values ranging from 12.10 to 14.20 µ g/mL. B. variegata is shown in Figure 8 Ephedra foeminea Non-flowering seed plants in the genus Ephedra are found throughout dry and semi-arid climates, especially in North Africa, Asia, America, and Europe [38] The ecological, commercial, and medicinal qualities of these plants make them valuable. According to a report, E. foeminea is used in herbal treatments for breast cancer in 68% of Palestinian women [39] According to earlier studies that examined E. foeminea ’ s phytochemical composition, it included 0.68% phenolic compounds, 0.01% alkaloids, and 0.06% flavonoids [40] Ephedrine is not a chemotype of E. foeminea , in contrast to other Ephedra species [41] Because it does not contain ephedrine, its pharmacological characteristics are different from those of other species. 18 distinct flavonoids, phenolics, 32 terpenes, organic acids, vitamins, and citric acid are all present in E. foeminea ’ s aqueous extract [42,43] E. foeminea is shown in Figure 9 Taxus brevifolia The North American plant T. Brevifolia is shown in Figure 10 . Sometimes referred to as Pacific yew or mountain mahogany, it grows along the coast from Alaska to California. Taxanes and diterpene alkaloids, such as Paclitaxel, Docetaxel, and 10-deacetylbaccatin III, which are important active principles in the taxane family, are its primary chemical constituents [44] Figure 7: Catharanthus roseus Figure 9: Ephedra foeminea Figure 8: Bauhinia variegata Figure 10: Taxus brevifolia

Kancharla and Samathoti: Medicinal plants with anti-breast cancer potential Asian Journal of Pharmaceutic s • Oct-Dec 2024 • 18 (4) | 1170 Paclitaxel was extracted from Yew tree bark extracts in 1964 and 1965 [45] Initially, the drug was sold under the name “Taxol.” In 1984, the FDA approved paclitaxel for use in chemotherapy and as a treatment for ovarian and breast cancer in 1992 [46] The USDA released paclitaxel, which was derived from T. brevifolia , in 1992. It has been demonstrated to have anticancer and antiangiogenic qualities in a variety of cancer cell lines, including those from the liver, prostate, lung, pancreas, and breast [47] Various medicinal plants and their phytochemical constituents are presented in Table 1 This article provides an overview of several plants along with information on their phytochemical composition. According to existing research on plants, all of these herbal plants contain phytochemical constituents such as myricetin, vincristine and vinblastine, glycyrrhizin, chalcones, tetrahydrocannabinol, saponins (avicins and Fo 35), quercetin, gallic acid, and withanolides. Which have already had their anticancer and antioxidant properties demonstrated. For this reason, it is expected that these plant materials will be useful in the treatment of breast cancer CONCLUSION This study investigates the potential of medicinal plants and their phytochemical components to prevent breast cancer. Conventional cancer treatments such as radiation therapy and chemotherapy have negative health effects, necessitating the use of complementary and alternative medicine. Medicinal plants contain novel anti-cancer agents, and traditional practitioners in countries such as Malaysia also use them. Table 1: Various medicinal plants and their phytochemical constituents S. No. Plant name Local name Family Phytochemical constituents 1. Caesalpinia pulcherrima Peacock flower Fabaceae Myricetin, flavonoids, homoflavonoids, β -Sitosterol, gallic acid, quercetin, rutin, lupeol, and elagic acid [15] 2 Glycyrrhiza glabra Liquorice Fabaceae Glycyrrhizin, chalcones, coumarins, flavonoids, isoflavones, and methylated isoflavones [17,18] 3 Securidaca longipedunculata Violet tree Polygalaceae Flavonoids, cardiac glycosides, phenols, alkaloids, saponins, and reducing sugar [21] 4 Perilla frutescens Beefsteak plant Lamiaceae Fatty acids, phenylpropane, terpenoids, polyphenols, [25] flavonoids, [26] anthocyanins, carotenoids, neolignans [27] 5 Catharanthus roseus Madagascar periwinkle Apocynaceae Vincristine and vinblastine [31] 6 Bauhinia variegata Orchid tree Fabaceae Quercetin, kaempferol, and rutin [35] 7 Ephedra foeminea Joint-pine, Brigham tea Ephedraceae Kaempferol, quercetin, catechin, limonene, stearic acid, vitamins, and citric acid [41] 8 Taxus brevifolia pacific yew Taxaceae Taxanes and paclitaxel [45] 9 Withania somnifera Indian Ginseng, Ashwagandha Solanaceae Withanolides, alkaloids, sitoindosides, and withaferin [48] 10 Andrographis paniculata Kalmegh Acanthaceae Andrographolide [49] 11 Cytisus villosus Hairybroom Leguminosae Epigallocatechin, quercetin derivatives, and kaempferol derivatives [50] 12. Hemidesmus indicus Sarasaparilla Apocynaceae Two-hydroxy-4-methoxybenzoic acid, three-hydroxy-4-methoxybenzaldehyde, and two-hydroxy-4-methoxybenzaldehyde [51] 13 Acacia victoriae Bardi bush Fabaceae Saponins (avicins and Fo 35) [52] 14 Vachellia tortilis Umbrella thron acacia Fabaceae Gallic acid, and epicatechingalloyled [53] 15 Annona muricata Raviola, Soursop, Sauersak Annonaceae Annonacin, [54] alkaloids, and flavonoids 16 Rhoicissus tridentata Bushman’s grape Vitaceae Alkaloids, terpenoids, flavonoids, and gallic acid [55] 17 Cannabis sativa Marihuana, and marijuana Cannabaceae Cannabinoids, tetrahydrocannabinol (THC), and cannabidiol (CBD) [56,57] 18 Linum usitatissimum Flax Linaceae Gallic acid, phenylpropanoids, and Linseed carotenoids [58]

Kancharla and Samathoti: Medicinal plants with anti-breast cancer potential Asian Journal of Pharmaceutic s • Oct-Dec 2024 • 18 (4) | 1171 A large number of secondary metabolites found in medicinal plants may be beneficial in treating breast cancer-causing chemicals by inhibiting their action. Therefore, this review lists various plants with anticancer properties and discusses each plant’s ability to prevent breast cancer. Researchers will use this information as a starting point for further research on these plants with anti-breast cancer action SUMMARY This review explores the potential of medicinal plants and bioactive substances in treating breast cancer. Breast cancer is a prevalent disease affecting millions of women worldwide. At present, chemotherapy is the most common treatment, but it has side effects. Thus, this review highlights the potential of herbal plants with bioactive compounds as potential anti-breast cancer treatments. This information could help beginners identify herbs with anti-breast cancer activity, paving the way for future research AUTHORS CONTRIBUTION Both authors have made an equal contribution AVAILABILITY OF DATA ACCESS The datasets of this study are available from the corresponding author on reasonable request ETHICS APPROVAL AND CONSENT TO PARTICIPATE Not applicable REFERENCES 1. Watkins EJ. Overview of breast cancer. JAAPA 2019;32:13-7 2. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209-49 3. PDQ Pediatric Treatment Editorial Board. Childhood acute lymphoblastic leukemia treatment (PDQ®). In: PDQ Cancer Information Summaries. Bethesda, MD: National Cancer Institute (US); 2024 4. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin 2021;71:7-33 5. Yousef AJ. Male breast cancer: Epidemiology and risk factors. Semin Oncol 2017;44:267-72 6. Kashyap D, Pal D, Sharma R, Garg VK, Goel N, Koundal D, et al . Global increase in breast cancer incidence: Risk factors and preventive measures. Biomed Res Int 2022;2022:9605439 7. Barbhuiya PA, Arman S, Paul H, Sen S, Dey BK, Pathak MP. An updated review on the early detection and drug development targeting breast cancer. Curr Womens Health Rev 2024;20:96-109 8. Khazir J, Mir BA, Pilcher L, Riley DL. Role of plants in anticancer drug discovery. Phytochem Lett 2014;7:173-81 9. Bonofiglio D, Giordano C, De Amicis F, Lanzino M, Ando S. Natural products as promising antitumoral agents in breast cancer: Mechanisms of action and molecular targets. Mini Rev Med Chem 2016;16:596-604 10. Kumar A, Jaitak V. Natural products as multidrug resistance modulators in cancer. Eur J Med Chem 2019;176:268-91 11. Greenwell M, Rahman PK. Medicinal plants: Their use in anticancer treatment. Int J Pharm Sci Res 2015;6:4103-12 12. Baraya YU, Wong KK, Yaacob NS. The immunomodulatory potential of selected bioactive plantbased compounds in breast cancer: A review. Anticancer Agents Med Chem 2017;17:770-83 13. Křížová L, Dadáková K, Kašparovská J, Kašparovský T. Isoflavones. Molecules 2019;24:1076 14. Dietz BM, Hajirahimkhan A, Dunlap TL, Bolton JL. Botanicals and their bioactive phytochemicals for women’s health. Pharmacol Rev 2016;68:1026-73 15. Sakle NS, More SA, Mokale SN. A network pharmacology-based approach to explore potential targets of Caesalpinia pulcherrima : An updated prototype in drug discovery. Sci Rep 2020;10:17217 16. Pastorino G, Cornara L, Soares S, Rodrigues F, Oliveira MB. Liquorice ( Glycyrrhiza glabra ): A phytochemical and pharmacological review. Phytother Res 2018;32:2323-39 17. Sharifi-Rad J, Quispe C, Herrera-Bravo J, Belén LH, Kaur R, Kregiel D, et al . Glycyrrhiza Genus: Enlightening phytochemical components for pharmacological and health-promoting abilities. Oxid Med Cell Longev 2021;2021:7571132 18. Hamad G, Elaziz A, Hassan S, Shalaby M, Mohdaly AA. Chemical composition, antioxidant, antimicrobial and anticancer activities of licorice ( Glycyrrhiza glabra L.) root and its application in functional yoghurt. J Food Nutr Res 2020;8:707-15 19. Jasim HA, Nahar L, Jasim MA, Moore SA, Ritchie KJ, Sarker SD. Chalcones: Synthetic chemistry follows where nature leads. Biomolecules 2021;11:1203 20. Alagawany M, Elnesr SS, Farag MR, Abd El-Hack ME, Khafaga AF, Taha AE, et al . Use of licorice ( Glycyrrhiza glabra ) herb as a feed additive in poultry: Current knowledge and prospects. Animals (Basel) 2019;9:536 21. Nizioł-Łukaszewska Z, Bujak T. Saponins as natural raw materials for increasing the safety of bodywash cosmetic

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