Current status and contemporary approaches to the discovery of antitumor agents from higher plants

Abstract

Higher plant constituents have afforded clinically available anticancer drugs. These include both chemically unmodified small molecules and their synthetic derivatives currently used or those in clinical trials as antineoplastic agents, and an updated summary is provided. In addition, botanical dietary supplements, exemplified by mangosteen and noni constituents, are also covered as potential cancer chemotherapeutic agents. Approaches to metabolite purification, rapid dereplication, and biological evaluation including analytical hyphenated techniques, molecular networking, and advanced cellular and animal models are discussed. Further, enhanced and targeted drug delivery systems for phytochemicals, including micelles, nanoparticles and antibody drug conjugates (ADCs) are described herein.

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

“…Therapeutic drugs derived from natural compounds have become of great interest since more than 75% of anticancer drugs were designed and developed from plant-derived natural ingredients which have been proven to have anticancer properties with novel mechanisms [6]. In the last 50 years, nearly 200 new chemical compounds have been approved to fight cancer, of which around 50% are molecules of unmodified natural products and their semisynthetic or synthetic derivatives that are safe and profitable [7,8]. Small organic molecules such as terpenes, flavonoids, alkaloids, lignans, saponins, vitamins, minerals, glycosides, oils, and other secondary metabolites play a significant role in either the inhibition of proliferation, induction of apoptosis, or other mechanisms that may be altered [9,10].…”

“…The biological models used for the development of new drugs include in vitro models using BrC cell lines and are divided into estrogen receptor positive (ER+, T47, MCF-7) and ER negative (ER-, MDA-MB-231, MDA-MB-453, SKBR3). MDA-MB-231 or triple-negative breast cancer cell (TNBC) line, estrogen negative (ER-) and progesterone negative (PR-), and HER-are known to be models for metastasis, which are more aggressive, containing a high potential to metastasize, and are unresponsive to antiestrogens [5,8]. TNBC line is used to investigate the mechanism underlying migration and invasion.…”

“…TNBC line is used to investigate the mechanism underlying migration and invasion. It is important to find cancer therapeutic compounds which possess multi-targeted and multifunctional potential with anti-metastasis activity [8,11]. MCF-7 is the most used cell line with a great number of publications due to the presence of ER+ [9].…”

“…">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].…”

“…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).…”