An updated pharmacological insight into calotropin as a potential therapeutic agent in cancer

Abstract

Calotropin is a pharmacologically active compound isolated from milkweed plants like Calotropis procera, Calotropis gigantea, and Asclepias currasavica that belong to the Asclepiadaceae family. All of these plants are recognised as medical traditional plants used in Asian countries. Calotropin is identified as a highly potent cardenolide that has a similar chemical structure to cardiac glycosides (such as digoxin and digitoxin). During the last few years, cytotoxic and antitumor effects of cardenolides glycosides have been reported more frequently. Among cardenolides, calotropin is identified as the most promising agent. In this updated and comprehensive review, we aimed to analyze and discuss the specific mechanisms and molecular targets of calotropin in cancer treatment to open new perspectives for the adjuvant treatment of different types of cancer. The effects of calotropin on cancer have been extensively studied in preclinical pharmacological studies in vitro using cancer cell lines and in vivo in experimental animal models that have targeted antitumor mechanisms and anticancer signaling pathways. The analyzed information from the specialized literature was obtained from scientific databases until December 2022, mainly from PubMed/MedLine, Google Scholar, Scopus, Web of Science, and Science Direct databases using specific MeSH search terms. The results of our analysis demonstrate that calotropin can be a potential chemotherapeutic/chemopreventive adjunctive agent in cancer pharmacotherapeutic management.

Combination of ethyl acetate fraction from Calotropis gigantea stem bark and sorafenib induces apoptosis in HepG2 cells

“…Since 2010, there has been considerable focus on studying the anticancer effects of C. gigantea extracts in many cancer models [25,26,[38][39][40][41]. However, biological activities involving C. gigantea stem bark extracts have rarely been conducted.…”

Unveiling the anti-cancer mechanisms of calotropin: Insights into cell growth inhibition, cell cycle arrest, and metabolic regulation in human oral squamous carcinoma cells (HSC-3)

“…1 × 10 5 HSC-3 cells were sown in each well of 96-well plates, and grown for 24 h and treated for 24 and 48 h. The glucose uptake test colorimetric kit was used in accordance with the directions provided by the manufacturer to measure glucose uptake. A pre-treatment with 5 mM and 10 mM d -glucose (2-DG) was given to HSC-3 cells at a population of 1 × 10 5 cells for 6 h before the intended drug treatment.…”

“…Plant-based natural remedies have the potential to provide therapies with fewer adverse reactions and equivalent or greater efficacy. 4 , 5 Medicinal plants have long been used in treating various diseases, including cancer, and they remain an essential resource for finding new drugs. 6 Despite their potential, many plants have yet to be thoroughly investigated for their anti-cancer activity specifically against oral squamous cell carcinoma.…”

Calotropin: Natural Phytomolecules for Cutting-edge Features

“…[58] Calotropin's IC 50 value on the human hepatocarcinoma cell line (HepG 2 ) and Raji cells (human B lymphoblastoid cell line) was revealed in a study, and values were reported as 0.04 µM and 0.02 µM, respectively; this validated the drug's cytotoxic action on tumor cell lines. [11,[59][60][61]…”

“…Calotropin is a highly potent cardenolide with a chemical composition equivalent to cardiac glycosides (such as digoxin and digitoxin). [9][10][11][12][13] Both species are widespread. However, Calotropis procera is more prevalent and has purple blooms, whereas Calotropis gigantea has whitish flowers.…”