A Review on Annona muricata and Its Anticancer Activity

Abstract

The ongoing rise in the number of cancer cases raises concerns regarding the efficacy of the various treatment methods that are currently available. Consequently, patients are looking for alternatives to traditional cancer treatments such as surgery, chemotherapy, and radiotherapy as a replacement. Medicinal plants are universally acknowledged as the cornerstone of preventative medicine and therapeutic practices. Annona muricata is a member of the family Annonaceae and is familiar for its medicinal properties. A. muricata has been identified to have promising compounds that could potentially be utilized for the treatment of cancer. The most prevalent phytochemical components identified and isolated from this plant are alkaloids, phenols, and acetogenins. This review focuses on the role of A. muricata extract against various types of cancer, modulation of cellular proliferation and necrosis, and bioactive metabolites responsible for various pharmacological activities along with their ethnomedicinal uses. Additionally, this review highlights the molecular mechanism of the role of A. muricata extract in downregulating anti-apoptotic and several genes involved in the pro-cancer metabolic pathways and decreasing the expression of proteins involved in cell invasion and metastasis while upregulating proapoptotic genes and genes involved in the destruction of cancer cells. Therefore, the active phytochemicals identified in A. muricata have the potential to be employed as a promising anti-cancer agent.

Keywords: Annona muricata; anticancer activity; bioactive metabolites; ethnomedicinal; pharmacological activities.

Figure 1

Diagram depicting the role of Phytochemicals (a) and bioactive metabolites present in Annona muricata (b).

Figure 2

Schematic representation of the types of acetogenins (a) and cell cycle machinery regulated by acetogenins (b).

Figure 3

Role of A. muricata in apoptosis. The figure was created with BioRender.com.

Figure 4

Representation of the role of MUC4 in pancreatic cancer (a) and action of graviola extract against lung cancer (b).

Figure 5

Schematic presentation of the anti-proliferative activity of graviola fruit extract against prostate cancer cell lines (a), the role of graviola against breast cancer cell line MCF-7 (b), and the molecular mechanism of A. muricata extract-treated HepG2 cell (c).

Figure 6

Schematic representation of molecular mechanisms of Annona muricata extracts against CRC (a), apoptosis induction in Annomuricin E treated HT-29 colorectal cancer cells (b), and apoptosis induction and mechanism of action in colorectal cancer-treated cell lines (c).

Figure 7

Schematic representation of (a) comparison of chemoradiotherapy treatment and combination of Cisplatin and Annona muricata extract treatment for HNSCC and their side effects and (b) globally diagnosed types of hematological malignancies.

Figure 8

Regulation of epithelial-mesenchymal transition (EMT) by signaling pathways. The EMT process is activated by many signaling pathways involving extracellular cytokines and receptor tyrosine kinases (RTKs). TGFβ is the master regulator, activating not just the canonical Smad signaling pathway but also numerous other signaling pathways. It has been shown that the Wnt/-catenin signaling pathway is also crucial to EMT. Upon activation of EMT, the transcription factors (TFs) of the snail family and mesenchymal genes are upregulated, while the epithelial genes are downregulated [165,175]. The figure was created with BioRender.com.