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Review
. 2023 Apr 17:14:1160616.
doi: 10.3389/fphar.2023.1160616. eCollection 2023.

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

Jovana Rajkovic  1 , Radmila Novakovic  1 , Jelica Grujic-Milanovic  2 , Alibek Ydyrys  3 , Nurzhanat Ablaikhanova  4 , Daniela Calina  5 , Javad Sharifi-Rad  6 , Basem Al-Omari  7
Affiliations
Review

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

Jovana Rajkovic et al. Front Pharmacol. .

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.

Keywords: anticancer; apoptosis; calotropin; cytotoxicity; molecular targets; signaling pathways.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Potential mechanisms of anticancer effects of calotropin in breast malignant tumor. Calotropin inhibits Ca2+ efflux via the Na+/Ca2+ exchanger, increasing intracellular Na+ and Ca2+, triggering apoptosis. Calotropin also induces apoptosis and cell death in tumour cells by disintegrating DNA and arresting the cell cycle in the G2/M phase. It also increases Bax/Bak1 expression and significantly reduces Bcl-2 expression, so this Bax/Bcl-2 ratio plays an important role in determining apoptosis. Symbols: ↑increase, ↓decrease.
FIGURE 2
FIGURE 2
Illustrative scheme with cytotoxic mechanisms of Calotropin in lung cancer. Abbreviations and symbols: ↑ increase, ↓decrease, Epithelial-mesenchymal transition (EMT), Reactive oxygen species (ROS), mitogen-activated protein (MAP) kinases and cJun NH2-terminal kinase (JNK), transforming growth factor β (TGF-β), cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4).
FIGURE 3
FIGURE 3
Schematic representation of anticancer mechanisms of calotropin in colorectal cancer.
FIGURE 4
FIGURE 4
Illustrative diagram with anti-leukemic mechanisms of calotropin. Symbols: ↑increase, ↓decrease.
See this image and copyright information in PMC

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