In Vitro and in Vivo antitumor activity and the mechanism of siphonodictyal B in human colon cancer cells

Cancer Medicine
Sonoko ChikamatsuChikashi Ishioka

Abstract

Liphagal, isolated from the marine sponge Aka coralliphaga, exhibits phosphatidylinositol 3-kinase alpha (PI3Kα) inhibitory activity and cytotoxic effects in human cancer cells. Siphonodictyal B, the biogenetic precursor of liphagal, also has PI3K inhibitory activity. However, its cytotoxic or antitumor activities have not been evaluated. In this study, we demonstrated that siphonodictyal B inhibits several kinases such as CDK4/6, CDK7, and PIM2 in addition to PI3K in vitro and that siphonodictyal B exhibits more potent cytotoxic effects than liphagal against human colon cancer cell lines. Furthermore, treatment with siphonodictyal B resulted in increased PARP cleavage, a larger sub-G1 fraction, and a larger annexin V-positive cell population, all of which are indicative of apoptosis induction. As a mechanism of apoptosis induction, we found that siphonodictyal B activates the p38 MAPK pathway, leading the upregulation of proapoptotic factors. Moreover, siphonodictyal B increased ROS levels, thus promoting p38 MAPK pathway activation. NAC, an ROS scavenger, almost completely reversed both the cytotoxic and p38 MAPK pathway-activating effects of siphonodictyal B. These results indicate that the p38 MAPK pathway might be involved...Continue Reading

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Citations

Jan 16, 2020·Journal of Clinical Medicine·Daniel Sur AlexandruIrimie
Mar 11, 2020·Pharmaceutics·Catarina Roma-RodriguesAlexandra R Fernandes
Apr 16, 2020·Cancers·Lizeth G Meza GuzmanSandra E Nicholson
Jan 4, 2021·Journal of Cancer Research and Clinical Oncology·Jiaen WeiZunnan Huang
Oct 11, 2020·Biochimica Et Biophysica Acta. General Subjects·Gan QiaoXiukun Lin

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Methods Mentioned

BETA
xenograft
Infrared Imaging
transfection
Assay
FACS
Flow cytometry
Flow

Software Mentioned

JMP Pro

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