Corosolic acid induces apoptotic cell death in HCT116 human colon cancer cells through a caspase-dependent pathway.
Corosolic acid (CA), a pentacyclic triterpene isolated from Lagerstroemia speciosa L. (also known as Banaba), has been shown to exhibit anticancer properties in various cancer cell lines. However, the anticancer activity of CA on human colorectal cancer cells and the underlying mechanisms remain to be elucidated. In this study, we investigated the effects of CA on cell viability and apoptosis in HCT116 human colon cancer cells. CA dose-dependently inhibited the viability of HCT116 cells. The typical hallmarks of apoptosis, such as chromatin condensation, a sub-G1 peak and phosphatidylserine externalization were detected by Hoechst 33342 staining, flow cytometry and Annexin V staining following treatment with CA. Western blot analysis revealed that CA induced a decrease in the levels of procaspase-8, -9 and -3 and the cleavage of poly(ADP-ribose) polymerase (PARP). The apoptotic cell death induced by CA was accompanied by the activation of caspase-8, -9 and -3, which was completely abrogated by the pan-caspase inhibitor, z-VAD‑FMK. Furthermore, CA upregulated the levels of pro-apoptotic proteins, such as Bax, Fas and FasL and downregulated the levels of anti-apoptotic proteins, such as Bcl-2 and survivin. Taken together, our data provide insight into the molecular mechanisms of CA-induced apoptosis in colorectal cancer (CRC), rendering this compound a potential anticancer agent for the treatment of CRC.
Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 609‑735, Republic of Korea.
Bokyung
B
Sung
Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 609‑735, Republic of Korea.
Yong Jung
YJ
Kang
Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 609‑735, Republic of Korea.
Dong Hwan
DH
Kim
Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 609‑735, Republic of Korea.
Seong Yeon
SY
Hwang
Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 609‑735, Republic of Korea.
Yujin
Y
Lee
Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 609‑735, Republic of Korea.
Minjeong
M
Kim
Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 609‑735, Republic of Korea.
Jeong-Hyun
JH
Yoon
Research Center for Anti‑Aging Technology Development, Pusan National University, Busan 609‑735, Republic of Korea.
Cheol Min
CM
Kim
Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 609‑735, Republic of Korea.
Hae Young
HY
Chung
Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 609‑735, Republic of Korea.
Nam Deuk
ND
Kim
D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002843:Chromatin / Q000378:metabolism; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D004789:Enzyme Activation / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects*; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*
D018797:Cell Cycle Proteins; D002843:Chromatin; D014315:Triterpenes; C113861:corosolic acid; D020169:Caspases