TABLE 1.

Anticancer effect of AA through different pathways.

Pathway	Effect of AA	Upregulated genes	Downregulated genes	Cell/Model organism	Reference
Cell Cycle Arrest	AA caused G2/M cell arrest and subG0 -G1 phase cell cycle arrest in MCF-7 cells. It also arrested NSCLC, PC-9 and H1975 cells at the G0/G1 phase	-	Cyclin D1, cdk4	MCF-7, NSCLC, PC-9, H1975	Haffez et al. (2022)
					Liu et al. (2019)
Mitochondrial Pathway	AA downregulated the Bcl-2 and upregulated the Bax, released Cyt-c from mitochondria, increased the expression of cleaved parp, and resulted in apoptosis in MCF-7 and NSCLC cells	Bax, Cleaved parp	Bcl-2	MCF-7, NSCLC	Haffez et al. (2022)
					Liu et al. (2019)
Extrinsic Apoptotic Pathway (EAP)	AA regulated the EAP through overexpression of apoptotic genes Fas, Fasl which further increased the expression of caspase-8, leading to activation of caspase-3 and apoptosis	Fas, Fasl, Caspase-8, Caspase-3	-	MCF-7	Haffez et al. (2022)
AMPK Pathway	AA downregulated PKC-a levels while overexpressing PRKAA1, a key kinase in MCF-7 resistance and metastasis cells. This overexpression activated AMPK.	PRKAA1	PKC-a	MCF-7	Haffez et al. (2022)
PI3K/Akt, ERK Pathways	AA caused a gradual decrease in PI3K protein levels and significantly inhibited Akt activation in a dose-dependent manner. There was no significant influence on phosphorylated p38 or phosphorylated ERK1/2	-	PI3K, Akt	Not specified	Hsieh et al. (2015)
Nuclear Factor Kappa B (NF-kB) Pathway	In NSCLC, AA downregulated the TNF-α induced activation of IKKβ, IkB and blocked the NF-kB nuclear translocation dose-dependently. AA directly bound to IKKβ, while its binding with IKKα was much lower, suggesting specificity for IKKβ. In addition, AA downregulated the proliferation (VEGF, IGFR1, TGF-β) and oncogenic genes (C-myc and NF-κB), and increased levels of antioxidants	-	IKKβ, IkB, VEGF, IGFR1, TGF-β, C-myc, NF-κB	NSCLC	Liu et al. (2019)
					Haffez et al. (2022)
Ferroptosis in Cancer	AA has a selective effect on inhibiting the viability of bladder cancer (BC) cell lines (J82, T-24, 5637) in a time and dose dependent manner. It has little effect on the normal urothelial cell line SV-HUC-1. AA induces ferroptosis in BC cells through upregulation of GPX4 which further affects the MDA, iron and GSH level in BC cells. AA treatment reduced lung metastasis of B16F10 cells in mice, resulting in lower mean lung weight and fewer countable nodules in the lungs compared to the control group. AA effectively reduced tumor size in mice with breast cancer xenografts, without affecting the mice’s body weight	GPX4, HMOX1, Nrf2, DDT3, ATF4, SOD1, HSPB1, P53, XBP1, catalase, GRX1, HO-1	-	BC (J82, T-24, 5637), SV-HUC-1, B16F10 (mice), Breast cancer xenografts (mice)	Xu et al. (2023)