Brevifoliol ester induces apoptosis in prostate cancer cells by activation of caspase pathway.
Balakishan BhukyaKaneez FatimaAbhishek NagarVijaya LakshmiPoornima DubeyShailesh KumarYogesh KumarSuaib LuqmanDebabrata ChandaSudeep TandonKaruna ShankerFeroz KhanArvind Singh NegiPublished in: Chemical biology & drug design (2019)
Prostate cancer is fourth most abundant cancer type around the globe. Brevifoliol, a rearranged taxoid from Taxus walllichiana needles has been derivatized as C5 esters using Steglich esterification reaction. Seventeen diverse analogues were evaluated against a panel of human cancer cell lines by MTT assay. Among these, two of the semi-synthetic analogues, that is, 13 and 16 exhibited potent cytotoxicity, selectively against PC-3, prostate cancer cell lines. In cell cycle analysis, analogue 13 induced S and G2/M phase arrest and induced apoptosis by activating caspase-3. Compound 13 showed moderate efficacy in in-vivo Ehrlich ascites carcinoma in Swiss albino mice. Further, compound 13 was found to be safe in Swiss albino mice up to 1,000 mg/kg dose in acute oral toxicity. Brevifoliol ester 13 may further be optimized for better efficacy.
Keyphrases
- induced apoptosis
- cell cycle
- prostate cancer
- signaling pathway
- endoplasmic reticulum stress
- oxidative stress
- papillary thyroid
- radical prostatectomy
- cell proliferation
- cell death
- squamous cell
- endothelial cells
- high fat diet induced
- molecular docking
- drug induced
- diabetic rats
- liver failure
- type diabetes
- high glucose
- lymph node metastasis
- childhood cancer
- respiratory failure
- high throughput
- structure activity relationship
- extracorporeal membrane oxygenation
- hepatitis b virus
- aortic dissection
- mechanical ventilation
- insulin resistance