Molecules (Nov 2021)

Anticancer Activity of Continentalic Acid in B-Cell Lymphoma

  • Byeol-Eun Jeon,
  • Chan-Seong Kwon,
  • Ji-Eun Lee,
  • Keumok Moon,
  • Jaeho Cha,
  • Inmyoung Park,
  • Sara Koh,
  • Myunghee Yoon,
  • Sang-Woo Kim,
  • Jeong Nam Kim

DOI
https://doi.org/10.3390/molecules26226845
Journal volume & issue
Vol. 26, no. 22
p. 6845

Abstract

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Aralia continentalis has been used in Korea as a folk remedy for arthralgia, rheumatism, and inflammation. However, its anti-lymphoma effect remains uncharacterized. Here, we demonstrate that A. continentalis extract and its three diterpenes efficiently kill B-lymphoma cells. Our in vitro and in vivo results suggest that the cytotoxic activities of continentalic acid, a major diterpene from A. continentalis extract, are specific towards cancer cells while leaving normal murine cells and tissues unharmed. Mechanistically, continentalic acid represses the expression of pro-survival Bcl-2 family members, such as Mcl-1 and Bcl-xL. It dissociates the mitochondrial membrane potential, leading to the stimulation of effector caspase 3/7 activities and, ultimately, cell death. Intriguingly, this agent therapeutically synergizes with roflumilast, a pan-PDE4 inhibitor that has been successfully repurposed for the treatment of aggressive B-cell malignancies in recent clinical tests. Our findings unveiled that A. continentalis extract and three of the plant’s diterpenes exhibit anti-cancer activities. We also demonstrate the synergistic inhibitory effect of continentalic acid on the survival of B-lymphoma cells when combined with roflumilast. Taken in conjunction, continentalic acid may hold significant potential for the treatment of B-cell lymphoma.

Keywords