Limonene and BEZ 235 induce apoptosis in COLO-320 and HCT-116 colon cancer cells

Raja Ratna Reddy Yakkanti, Manisha Singh, Vasanti Kabra, P. Chandra Sekhar, K. SreejaVamsi, B. Ramachandra Reddy, S Ramamoorthy, C. Damodar Reddy

DOI: http://dx.doi.org/10.5138/09750215.2240

Abstract


Deregulated apoptosis is the hall mark of many cancers, therefore every defect in apoptosis pathway could be a potential target for cancer treatment.The anticancer mechanism of limonene could be multifactorial. However, induction of apoptosis in cancer cells is proposed as the predominant mechanism in several of preclinical studies. Therefore, we determined to investigate the role of apoptosis in the anticancer activity of limonene and BEZ235 combination in COLO-320 and HCT-116 colon cancer cells. Cells after treatments were assessed for apoptosis by DAPI staining for fluorescent microscopic examination of apoptotic cells, estimation of caspases activities, Bcl-2 family proteins in addition to cell cycle analysis by flowcytometry. Results show that both drugs induced apoptosis as demonstrated by increased caspases activity, significant alterations in pro and anti-apoptotic proteins of Bcl-2 family in promoting apoptosis and cell cycle arrest at G1 phase. Over all, it is indicated that limonene and BEZ exerted anticancer activity is mediated through induction of apoptosis involving mitochondria mediated intrinsic death pathway in the selected CRC cells.


Keywords


Colorectal cancer, limonene, BEZ, apoptosis, caspases.

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