The present study relates to the induction of apoptosis thereof cytotoxicity and anti-cancer activity displayed by semi-synthetic
analog of Boswellic acid i.e. 3-α-Butyryloxy-β-boswellic acid (BOBA). The cytotoxicity data revealed the differential sensitivity of
cancer cell lines towards BOBA which may display its impact against different types of cancers. Considering the inhibitory potential of
BOBA, we further sought to understand the target for BOBA deciphering the mechanism of action leading to apoptotic cell death and it
was for the first time reported about the triterpenoid ring especially the β-boswellic acid derivative is targeting PI3K pathway. Our data
revealed that BOBA treatment provides evidence about the apoptotic nature showing the potential of targeting mitochondria dependent
pathways during apoptosis in HL-60 cells. BOBA induced hypo-diploid sub-G1 DNA population in HL-60 cells as was also evident from
the pattern of DNA fragmentation and mitochondrial membrane potential (ΛΨm) loss. Morphological analysis under fluorescent and
scanning electron microscopy displayed typical features such as cell shrinkage, membrane blebbing, chromatin condensation and nuclear
fragmentation. These events paralleled with the down-regulation of NF-κB and induced PARP cleavage. Furthermore, it is noteworthy
that BOBA also depicted significant growth inhibition in Ehrlich Ascitic Tumour (EAT), Ehrlich Ascitic Carcinoma (EAC) and Sarcoma-
180 tumour models. Taken together, BOBA treatment may represent as potential agent to the currently available anticancer agents in both
prophylactic and/or therapeutic applications. Also, our findings may open up a new perspective in the construction of novel anticancer
agents based on boswellic acids that will facilitate the development of these agents for anticancer therapeutics.
Keywords: DNA repair, Apoptosis, Cancer, Natural Products, Drug, Signaling, PI3K, Boswellia serrata.
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