A novel guaiane sesquiterpene derivative, guai-2-en-10α-ol, from Ulva fasciata 
Delile exhibits antimicrobial property. U. fasciata extract was reported to 
exhibit cytotoxicity against cancer. In the present study, we have studied the 
anticancer potential of the compound, guai-2-en-10α-ol, from U. fasciata. The 
compound showed selective cytotoxicity toward triple-negative breast cancer 
(TNBC) cell line (MDA MB-231) in a dose-dependent manner. In treated cells, the 
apoptotic hallmarks such as formation of apoptotic bodies, cell shrinkage, and 
nuclear condensation were observed. Many small molecules affect the function of 
cellular signaling pathways. As EGFR/PI3K/Akt pathway proteins are frequently 
altered in TNBC, we have studied the gene expression of key proteins of this 
pathway. The semiquantitative PCR results demonstrated the down-regulated 
expression of PDPK1 (positive regulator) and Akt (key activator) as well as 
up-regulated expression of PTEN (negative regulator), which suggested the 
interaction of guai-2-en-10α-ol with upstream protein. Further investigation 
showed the down-regulation of both PI3K and EGFR. As EGFR is the most upstream 
protein of the pathway, its protein level expression was investigated. Western 
blotting analysis confirmed the down-regulation of p-EGFR expression and 
activation of apoptosis upon compound treatment. Cell cycle analysis also 
evidenced the G1 phase arrest, which can be due to the inhibition of cell 
survival pathway. Computational studies showed the interaction of 
guai-2-en-10α-ol with Asp855 residue of EGFR kinase domain in active 
conformation. All these results demonstrate the anticancer potential of 
guai-2-en-10α-ol through EGFR/PI3K/Akt pathway.