Bioassay Guided Identification of Small Chaperone Proteins α-crystallin and Hsp27 Inhibitors from Copaiba Oil

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Phytochemistry Letters


Over-expression of small chaperone proteins in cancer tissue contributes to the resistance of chemotherapy. Targeting these small chaperones including α-crystallin and heat shock protein 27 (Hsp27) is a promising strategy for cancer treatment. Hardwickiic acid (HA), a clerodane diterpenoid from Copaiba oil has been reported to inhibit Hsp27. We expect to identify new small chaperone inhibitors from Copaiba oil that is abundant of diterpenoids. In the current study, cytotoxicity and anti-chaperone assay guided isolation of Copaiba oil led to two major fractions (non-acidic and acidic components) and seven sub-fractions from the acidic components. The non-acidic components and one sub-fraction showed significant cytotoxicity in prostate cancer cells. Four sub-fractions exhibited potent anti-chaperone activity. Three chemical components were identified from these sub-fractions including copalic acid, hardwickiic acid and 3-acetoxycopalic acid. All three compounds inhibited the chaperone activities of α-crystallin and Hsp27. In addition, these compounds enhanced the anti-proliferative activity of the chemotherapeutic agent carboplatin in LNCaP cells. 3-Acetoxycopalic acid slightly decreased the level of Hsp27 client protein signal transducer and activator of transcription 3 (Stat3) in PC3 cells. Overall, several diterpenoids were identified to be small chaperone inhibitors and could be used as lead compounds for the development of more potent derivatives.


This research was supported by Center for Gene Regulation in Health and Disease (GRHD) of Cleveland State University and Ohio Department of Development (ODOD), and also supported by CSU Undergraduate Research and Creative Achievement award from CSU.