Prunin: An Emerging Anticancer Flavonoid

Abstract

Despite the substantial advances in cancer therapies, developing safe and effective treatment methodologies is critical. Natural (plant-derived compounds), such as flavonoids, might be crucial in developing a safe treatment methodology without toxicity toward healthy tissues. Prunin is a flavonoid with the potential to be used in biomedical applications. Prunin has yet to undergo thorough scientific research, and its precise molecular mechanisms of action remain largely unexplored. This review summarizes the therapeutic potential of prunin for the first time, focusing on its underlying mechanisms as an anticancer compound. Prunin has gained significant attention due to its antioxidant, anti-inflammatory, and anticancer effects. This review aims to unlock how prunin functions at the molecular level to exert its anticancer effects, primarily modulating key cellular pathways. Furthermore, we have discussed the prunin's potential as an adjunctive therapy with conventional treatments, highlighting its ability to strengthen treatment responses while decreasing drug resistance. Moreover, the discussion probes into innovative delivery methods, particularly nanoformulations, that might address prunin's bioavailability, solubility, and stability limitations and optimize its therapeutic application. By providing a comprehensive analysis of prunin's properties, this review aims to stimulate further exploration of using prunin as an anticancer agent, thereby progressing the development of targeted, selective, safe, and effective therapeutic methods.

Keywords: anticancer; combination therapy; flavonoid; nanoformulation; natural compounds; prunin.

Figure 7

Overview of prunin for combination treatment and nanoformulation for improved drug delivery. Prunin can be utilized alongside radiation, nanoparticles, various natural compounds, and anticancer chemotherapy drugs to achieve a synergistic effect, helping to reduce drug resistance and enhance cell activity and death. For drug delivery, the nanoformulation increases the bioavailability, solubility, stability, target delivery, and overall efficiency of the prunin [310,311,312]. The figure was prepared using Biorender.

Figure 1

The chemical structure of Prunin and its primary biological effects. (A) Chemical structure of prunin. (B) Primary biological effects of prunin. Prunin demonstrates various pharmacological properties, including anticancer activity, anti-inflammatory effects, antimicrobial effects, immune regulation, anti-osteoporosis, anti-hypoxia, and protective effects. These benefits highlight the potential of Prunin as a versatile therapeutic compound. The figure was prepared using Biorender (BioRender.com accessed on 13 March 2025).

Figure 2

The biological significance of prunin. Prunin influences multiple pathways in tumor cells at the molecular level, ultimately inducing key therapeutic effects such as cell cycle arrest, apoptosis, antiproliferation, and anti-angiogenesis, as well as anti-metastasis and invasion. The figure was prepared using Biorender.

Figure 3

Prunin influences cell cycle regulation by interacting with various CDKs and cyclins. Prunin is helpful for modifying CDKs and cyclins during different cycle phases. It can inhibit CDK4, CDK6, and cyclin D action by increasing the expressions of the p21 marker in the G₁ phase. At the G₁/S checkpoint, prunin suppresses CDK2-Cyclin E by increasing p21 expressions. Similarly, CDK2-Cyclin A activity is restricted by the p27 marker [166,167,168]. This highlights the potential of flavonoids such as prunin to influence or induce cell cycle arrest, which contributes to cancer treatment. The figure was prepared using Biorender.

Figure 4

The prunin compound induces apoptosis by triggering intrinsic and extrinsic-mediated pathways. In the extrinsic pathway, the prunin compound activates the FAS receptor, triggering FADD and cleaving pro-caspase-8/10. The activated caspase-8 processes BID into tBID, effectively linking the extrinsic pathway to the intrinsic pathway by enhancing the permeabilization of the outer mitochondrial membrane. In the intrinsic pathway, prunin can cause mitochondrial dysfunction by influencing endogenous ROS levels and altering the balance between pro-apoptotic and anti-apoptotic proteins [172,174,175]. The figure was prepared using Biorender.

Figure 5

The prunin compound induces activation of P53 pathways. The prunin stimulates the P53 pathways after receiving the DNA damage signal, which further leads to multiple tasks, including cell cycle arrest, DNA repair if the damage is moderate, senescence, and apoptosis [84,226,227]. The apoptosis mechanism is highlighted when DNA damage stimulation occurs by prunin. It increases the activation of ATM, ATR, CHK1, and CHK2, which further leads to the activation of its downstream marker P53. The P53 further activates BAX and caspase cascades to induce apoptosis in cancer cells [228]. The figure was prepared using Biorender.

Figure 6

Overview of the immunomodulatory effects of prunin on innate and adaptive immune responses. Activation (black arrow), increased response (red arrow). The figure was prepared using Biorender.