Cytotoxic Effect and Mechanisms from Some Plant-Derived Compounds in Breast Cancer

Abstract

Breast cancer (BrC) is a major health problem in women all around the world. A growing knowledge about these alterations and their associated molecular signaling pathways offers opportunities for therapeutic strategies; chemotherapy is one of the most utilized treatments; however, because of the adverse side effects and multidrug resistance that patients may present, there has been great advancement in search of new alternatives as the use of plant-derived natural compounds. This review describes information on the progress and development of cytotoxic compounds against BrC belonging to the families of flavonoids, terpenes, and alkaloids that through in vitro and in vivo studies have demonstrated to induce cellular death mainly through apoptosis, activating the intrinsic pathway. The in vitro IC 50 and the in vivo EC 50 dose-response relationship can vary depending on various factors, including the choice of cell line and/or the model used. Also, the association of some of these compounds with nanoparticles or paclitaxel with antibodies has clearly shown a potential improvement in its effect. The clinical studies that are being conducted with some of them show promising results; however, it is necessary to continue with the effort to develop new and more effective drugs against different types of BrC.Cytotoxic Effect and Mechanisms from Some In vivo models for studying plant-derived compounds in breast cancerWide varieties of animal model systems are now available to investigate plantderived compounds in different stages, such as cancer initiation, promotion progression, invasion, and metastasis. These models are also used to comprehend therapeutic response, which represents an essential step between in vitro systems and clinical studies [8,13]. The in vivo models are also used to investigate the capability of plant formulation to induce an anti-BrC effect where it is sought to optimize dose, bioavailability, administration routes, and selective delivery and reduce toxic effects, among others [8,14]. The two animal species that will be mentioned in this review are those involving mice and rats [14]; however, BrC mouse models are used in a variety of preclinical studies [13].There are different types of in vivo models of BrC, such as cell line-derived xenografts (MDA-MB-231 line) that are implanted into immunocompromised animals (cell-derived xenografts, CDX). CDX models represent a relatively homogenous mass of transformed breast epithelial cells, and depending on where the cells are inoculated, they are classified as ectopic CDX (models advanced disease only, subcutaneous injection of human tumor cells), orthotopic CDX (in mammary gland/fat pad), metastatic CDX (following tail vein or intra-cardiac injection in specific sites, i.e., bone or lung), syngeneic (mouse tissue implanted to strainmatched host) or metastasis with syngeneic model (usually fast-growing tumors and microenvironment derive from the same species, i.e., 4T1 cells), and genetically engineered mouse models (GEMMs) to address early events of tu...

Evaluation of Chemical Composition, Antibacterial, Antifungal, and Cytotoxic Activity of Laurus nobilis L Grown in Saudi Arabia

“…Plant derived compounds have different modes of action; however, most of them induce apoptosis without cytotoxic effect on normal cells 54 . Recently it was reported that in phenols, the number of substitutes in the OH-ring, increases its anti-proliferative and cytotoxic activities 55 . Similarly, terpenes, terpenoids, alkaloids and flavonoids induce cytotoxicity of breast cancer cells by activating the intrinsic pathway resulting in apoptosis 55 .…”

“…Recently it was reported that in phenols, the number of substitutes in the OH-ring, increases its anti-proliferative and cytotoxic activities 55 . Similarly, terpenes, terpenoids, alkaloids and flavonoids induce cytotoxicity of breast cancer cells by activating the intrinsic pathway resulting in apoptosis 55 . Significant cytotoxic and antitumor activity of methanol and aqueous extracts of L. nobilis leaves towards a number of cancer cell lines, like NCI-H460-lung cancer cells, cervical carcinoma, HCT15-colon carcinoma, breast adenocarcinoma and HepG2 -hepatocellular carcinoma have been reported earlier.…”

α-Mangostin Nanoparticles Cytotoxicity and Cell Death Modalities in Breast Cancer Cell Lines

“…Over 200 novel chemical compounds have been licensed for use in the battle against cancer in the last 50 years, with about 50% being molecules of unaltered natural products [ 21 ]. Small organic molecules of secondary metabolites have played an essential role in inhibiting proliferation-induced apoptosis or other modifiable mechanisms [ 22 , 23 , 24 ].…”

Potential Treatment of Breast and Lung Cancer Using Dicoma anomala, an African Medicinal Plant

“…The mechanism of action of plant-derived bioactive compounds involves inhibition of various cellular activities, and the potency of plant-derived chemical agents is dependent on the dosage [ 30 ]. Figure 2 illustrates various steps involved in tumor development and its fate.…”