Anti-cancer effect of a phytochemical compound - 7R-acetylmelodorinol - against triple-negative breast cancer cells

Chutamas Thepmalee; Nunghathai Sawasdee; Phanitaporn Jenkham; Chonthida Thephinlap; Krissana Khoothiam; Nittiya Suwannasom; Ratchanaporn Chokchaisiri; Aussara Panya; Pa-Thai Yenchitsomanus

doi:10.1016/j.biopha.2023.115286

Anti-cancer effect of a phytochemical compound - 7R-acetylmelodorinol - against triple-negative breast cancer cells

Biomed Pharmacother. 2023 Oct:166:115286. doi: 10.1016/j.biopha.2023.115286. Epub 2023 Aug 12.

Authors

Chutamas Thepmalee¹, Nunghathai Sawasdee², Phanitaporn Jenkham³, Chonthida Thephinlap³, Krissana Khoothiam⁴, Nittiya Suwannasom³, Ratchanaporn Chokchaisiri⁵, Aussara Panya⁶, Pa-Thai Yenchitsomanus²

Affiliations

¹ Unit of Excellence on Research and Development of Cancer Therapy, University of Phayao, Phayao 56000, Thailand; Division of Biochemistry, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand. Electronic address: th.chutamas@gmail.com.
² Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
³ Unit of Excellence on Research and Development of Cancer Therapy, University of Phayao, Phayao 56000, Thailand; Division of Biochemistry, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand.
⁴ Unit of Excellence on Research and Development of Cancer Therapy, University of Phayao, Phayao 56000, Thailand; Division of Microbiology, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand.
⁵ Department of Chemistry, School of Science, University of Phayao, Phayao 56000, Thailand.
⁶ Cell Engineering for Cancer Therapy Research Group, Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand.

PMID: 37573655
DOI: 10.1016/j.biopha.2023.115286

Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive subtype currently lacking effective treatment options. Consequently, novel and effective drugs or compounds are urgently needed to treat TNBC. Therefore, this study aimed to evaluate the potential of 7R-acetylmelodorinol (7R-AMDL), a phytochemical compound isolated from Xylopia pierrei Hance, a plant found in Thailand, as a novel therapeutic agent for TNBC. MTT and clonogenic assays showed that 7R-AMDL significantly reduced the survival of breast cancer cell lines, with a markedly potent effect on MDA-MB-231 cells. Flow cytometry showed that treating MDA-MB-231 cells with 7R-AMDL at the concentration of dose 8 µM significantly increased early and late apoptosis after 24 and 48 h compared to the control group (p < 0.0001). The highest tested 7R-AMDL dose upregulated the death receptors and their ligands, with extrinsic and intrinsic apoptosis pathways significantly activated via the caspase cascade, compared to the untreated group (p < 0.05). In addition, immunoblots showed decreased BCL2-like 1 (BCL2L1/Bcl-xL) expression (p < 0.0001). Furthermore, wound healing and Transwell assays showed that at a non-cytotoxic dose (≤4 µM), 7R-AMDL significantly inhibited the MDA-MB-231 cell migration and invasion. This reduction in cell migration was associated with decreased matrix metallopeptidase 9 (MMP-9) expression (p < 0.01) and nuclear factor kappa B (NF-κB) activation (p < 0.05). Altogether, 7R-AMDL has anti-cancer effects against TNBC and the potential to be further developed and evaluated for treating this disease.

Keywords: 7R-acetylmelodorinol; Anti-cancer effect; Anti-metastasis effect; MDA-MB-231; Triple-negative breast cancer (TNBC).

MeSH terms

Apoptosis
Cell Line, Tumor
Cell Proliferation
Humans
NF-kappa B / metabolism
Signal Transduction
Triple Negative Breast Neoplasms* / drug therapy
Triple Negative Breast Neoplasms* / metabolism

Substances

NF-kappa B