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Cycloartobiloxanthone Induces Human Lung Cancer Cell Apoptosis via Mitochondria-dependent Apoptotic Pathway

Nattanan Losuwannarak1,2, Boonchoo Sritularak3, Pithi Chanvorachote4,2

  • 1Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.

In Vivo (Athens, Greece)
|December 25, 2017
PubMed
Abstract

Insights

Cycloartobiloxanthone, a natural compound, effectively kills lung cancer cells by inducing apoptosis through a mitochondria-dependent pathway. This flavonoid shows promise as a novel anticancer therapeutic agent.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Lung cancer remains a significant global health challenge, necessitating the development of novel therapeutic agents.
  • Cycloartobiloxanthone, a flavonoid derived from Artocarpus gomezianus, presents potential as an anticancer drug.

Purpose of the Study:

  • To evaluate the anticancer activity of cycloartobiloxanthone against human lung cancer cell lines.
  • To elucidate the mechanism of action, specifically focusing on apoptosis induction and the involvement of the mitochondrial pathway.

Main Methods:

  • Cytotoxicity was assessed using the MTT assay on lung cancer cell lines (H23, H460, H292, A549).
  • Apoptosis was analyzed via Hoechst 33342/propidium iodide staining.
  • Western blot analysis was employed to examine key proteins in the mitochondria-dependent apoptotic pathway.

Main Results:

  • Cycloartobiloxanthone demonstrated potent cytotoxic effects on both small and non-small cell lung cancer.
  • Apoptotic cell death was confirmed as the primary mechanism, comparable to cisplatin and etoposide.
  • The compound activated p53, upregulated pro-apoptotic BAX, downregulated anti-apoptotic BCL2 and MCL1, and increased cleaved caspase-9, caspase-3, and PARP, indicating activation of the intrinsic apoptotic pathway.

Conclusions:

  • Cycloartobiloxanthone exhibits significant anticancer activity against human lung cancer cells.
  • The mechanism involves the induction of mitochondrial apoptotic, caspase-dependent pathways.
  • This compound holds promise for future cancer therapy development.
Keywords:
BAXCycloartobiloxanthoneMCL1apoptosislung cancermitochondria-dependent apoptotic pathway

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