Repurposing of plant alkaloids for cancer therapy: Pharmacology and toxicology.

Abstract

Drug repurposing (or repositioning) is an emerging concept to use old drugs for new treatment indications. Phytochemicals isolated from medicinal plants have been largely neglected in this context, although their pharmacological activities have been well investigated in the past, and they may have considerable potentials for repositioning. A grand number of plant alkaloids inhibit syngeneic or xenograft tumor growth in vivo. Molecular modes of action in cancer cells include induction of cell cycle arrest, intrinsic and extrinsic apoptosis, autophagy, inhibition of angiogenesis and glycolysis, stress and anti-inflammatory responses, regulation of immune functions, cellular differentiation, and inhibition of invasion and metastasis. Numerous underlying signaling processes are affected by plant alkaloids. Furthermore, plant alkaloids suppress carcinogenesis, indicating chemopreventive properties. Some plant alkaloids reveal toxicities such as hepato-, nephro- or genotoxicity, which disqualifies them for repositioning purposes. Others even protect from hepatotoxicity or cardiotoxicity of xenobiotics and established anticancer drugs. The present survey of the published literature clearly demonstrates that plant alkaloids have the potential for repositioning in cancer therapy. Exploitation of the chemical diversity of natural alkaloids may enrich the candidate pool of compounds for cancer chemotherapy and -prevention. Their further preclinical and clinical development should follow the same stringent rules as for any other synthetic drug as well. Prospective randomized, placebo-controlled clinical phase I and II trials should be initiated to unravel the full potential of plant alkaloids for drug repositioning.

• Authors: Thomas Efferth, Franz Oesch
• Journal: Seminars in cancer biology (Semin Cancer Biol) Vol. 68 Pg. 143-163 (01 2021) ISSN: 1096-3650 [Electronic] England
• PMID: 31883912 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• Alkaloids
• Antineoplastic Agents
• Phytochemicals

Topics

• Alkaloids (pharmacology, toxicity)
• Animals
• Antineoplastic Agents (pharmacology)
• Drug Discovery
• Drug Repositioning (methods)
• Humans
• Neoplasms (drug therapy)
• Phytochemicals (pharmacology, toxicity)
• Toxicity Tests