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2024;19 (4): e0296989.

AM-18002, a derivative of natural anmindenol A, enhances radiosensitivity in mouse breast cancer cells.

Da-Young Eum, Myeonggyo Jeong, Soon-Yong Park, Jisu Kim, Yunho Jin, Jeyun Jo, Jae-Woong Shim, Seoung Rak Lee, Seong-Joon Park, Kyu Heo, Hwayoung Yun, Yoo-Jin Choi
Author Information
  1. Da-Young Eum: Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, Republic of Korea.
  2. Myeonggyo Jeong: College of Pharmacy, Pusan National University, Busan, Republic of Korea.
  3. Soon-Yong Park: Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, Republic of Korea.
  4. Jisu Kim: College of Pharmacy, Pusan National University, Busan, Republic of Korea.
  5. Yunho Jin: Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, Republic of Korea.
  6. Jeyun Jo: College of Pharmacy, Pusan National University, Busan, Republic of Korea.
  7. Jae-Woong Shim: Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, Republic of Korea.
  8. Seoung Rak Lee: College of Pharmacy, Pusan National University, Busan, Republic of Korea.
  9. Seong-Joon Park: Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, Republic of Korea.
  10. Kyu Heo: Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, Republic of Korea.
  11. Hwayoung Yun: College of Pharmacy, Pusan National University, Busan, Republic of Korea. ORCID
  12. Yoo-Jin Choi: Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, Republic of Korea. ORCID
PMID: 38625901 DOI: 10.1371/journal.pone.0296989

Abstract

Natural anmindenol A isolated from the marine-derived bacteria Streptomyces sp. caused potent inhibition of inducible nitric oxide synthase without any significant cytotoxicity. This compound consists of a structurally unique 3,10-dialkylbenzofulvene skeleton. We previously synthesized and screened the novel derivatives of anmindenol A and identified AM-18002, an anmindenol A derivative, as a promising anticancer agent. The combination of AM-18002 and ionizing radiation (IR) improved anticancer effects, which were exerted by promoting apoptosis and inhibiting the proliferation of FM3A mouse breast cancer cells. AM-18002 increased the production of reactive oxygen species (ROS) and was more effective in inducing DNA damage. AM-18002 treatment was found to inhibit the expansion of myeloid-derived suppressor cells (MDSC), cancer cell migration and invasion, and STAT3 phosphorylation. The AM-18002 and IR combination synergistically induced cancer cell death, and AM-18002 acted as a potent anticancer agent by increasing ROS generation and blocking MDSC-mediated STAT3 activation in breast cancer cells.

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MeSH Term

Mice
Animals
Reactive Oxygen Species
Sesquiterpenes
Antineoplastic Agents
Apoptosis
Radiation Tolerance
Cell Proliferation
Cell Line, Tumor
Neoplasms
Indenes

Chemicals

anmindenol A
Reactive Oxygen Species
Sesquiterpenes
Antineoplastic Agents
Indenes
Journal Article

Word Cloud

Created with Highcharts 10.0.0AM-18002canceranmindenolcellsanticancerbreastpotentderivativeagentcombinationIRmouseROScellSTAT3Naturalisolatedmarine-derivedbacteriaStreptomycesspcausedinhibitioninduciblenitricoxidesynthasewithoutsignificantcytotoxicitycompoundconsistsstructurallyunique310-dialkylbenzofulveneskeletonpreviouslysynthesizedscreenednovelderivativesidentifiedpromisingionizingradiationimprovedeffectsexertedpromotingapoptosisinhibitingproliferationFM3AincreasedproductionreactiveoxygenspecieseffectiveinducingDNAdamagetreatmentfoundinhibitexpansionmyeloid-derivedsuppressorMDSCmigrationinvasionphosphorylationsynergisticallyinduceddeathactedincreasinggenerationblockingMDSC-mediatedactivationnaturalenhancesradiosensitivity

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