Cajanol

Cajanol is an isoflavanone isolated from the roots of pigeon pea [Cajanus cajan (L.) Millsp.]. It inhibits cancer cell proliferation and induces apoptosis. Cajanol increases Bax expression, inhibits Bcl-2 expression, activates caspase-9 and caspase-3, induces PARP cleavage, arrests the cell cycle at the G2/M phase, generates ROS, disrupts mitochondrial membrane potential, and triggers cytochrome c release. Additionally, cajanol induces bacterial DNA damage, disrupts bacterial cell membranes, and exhibits antibacterial activity in vitro. It reduces PI3K expression, inhibits Akt and NF-κB phosphorylation, downregulates P-gp expression and transport function, restores sensitivity of resistant cancer cells to Paclitaxel, and suppresses the growth of Paclitaxel-resistant metastatic ovarian tumors. Cajanol is applicable in research related to breast cancer, ovarian cancer, and bacterial infections.

Cajanol exhibits potent time and dose-dependent inhibition of human breast cancer MCF-7 cell growth with IC50 values of 83.42 μM at 24 hours, 58.32 μM at 48 hours, and 54.05 μM at 72 hours when applied at concentrations of 0-316 μM over 24-72 hours. At concentrations of 16-64 μM over 48 hours, Cajanol induces concentration-dependent G2/M phase cell cycle arrest, apoptosis, DNA fragmentation, typical apoptotic nuclear morphological changes, ROS generation, and mitochondrial membrane potential disruption in MCF-7 cells. It also activates caspase-3 and caspase-9, downregulates Bcl-2 expression, upregulates Bax expression, promotes the release of cytochrome c from mitochondria into the cytoplasm, and leads to concentration-dependent PARP cleavage. Additionally, Cajanol inhibits the growth of both Gram-positive bacteria (Staphylococcus epidermidis, Staphylococcus aureus, Bacillus subtilis) and Gram-negative bacteria (Escherichia coli, Proteus vulgaris, Pseudomonas aeruginosa) in vitro, with the most sensitive strains (Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli) having MIC values of 98.90 μM, and less sensitive strains (Bacillus subtilis, Proteus vulgaris, Pseudomonas aeruginosa) showing MIC values of 197.8 μM. In vitro, Cajanol also induces time-dependent cell death and membrane damage in Escherichia coli and Staphylococcus aureus strains over 4-10 hours, including DNA cleavage. It demonstrates concentration-dependent reversal of Paclitaxel resistance in A2780/Taxol and A549/Taxol cells at 2-16 μM over 72 hours. Additionally, Cajanol suppresses ABCB1 mRNA expression and P-gp protein in A2780/Taxol cells at 2-8 μM over 48 hours and inhibits the PI3K/Akt/NF-κB signaling pathway through concentration-dependent reduction of PI3K expression, inhibition of Akt phosphorylation, and blocking of NF-κB/p65 phosphorylation and nuclear translocation. Finally, Cajanol (2-8 μM; 2 hours pre-incubation, 1 hour co-incubation with rhodamine-123) concentration-dependently inhibits P-gp mediated efflux activity in A2780/Taxol cells, increasing intracellular accumulation of rhodamine-123.

Cajanol (2 mM/kg; intravenous injection; administered on days 1, 8, and 15 post-tumor implantation) reduces the volume of Paclitaxel-resistant ovarian tumors to 680 mm³ after 24 days. When combined with Paclitaxel, the tumor volume significantly decreases to 182.4 mm³, while the body weight of mice is maintained.