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Anticancer potential of β-isopropylfuran-1,2-naphthoquinone in different types of tumor cell lines
Tamiles Caroline Fernandes Pedrosa1, Adriana Cotta Cardoso Reis1, Kamila de Fátima da Anunciação2
1Programa de Pós-Graduação em Ciências Farmacêuticas (CiPharma), Faculdade de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, Brasil.
Abstract:
Cancer is a multifactorial disease characterized by uncontrolled cell growth and remains a major global health challenge. Given the limitations of conventional therapies, naturally derived compounds such as naphthoquinones have attracted interest for their antitumor potential. This study evaluated the in vitro effects of β-isopropylfuran-1,2-naphthoquinone (NAF-Q69), a synthetic isolapachol derivative, on different cell lines (MRC-5 - human lung fibroblasts; HEPG2 - hepatocellular carcinoma; HeLa - cervical cancer; TOV - ovarian adenocarcinoma; MDA-MB - breast adenocarcinoma; and J82 - urothelial carcinoma) to assess its cytotoxic activity and cellular characteristics (clonogenic survival, migration, morphology, cell cycle, and reactive oxygen species \[ROS] production). NAF-Q69 showed significant dose-dependent cytotoxicity in all tumor lines, with IC50 values ranging from 10.29 µM (MDA-MB) to 18.65 µM (HEPG2). It decreased viability, inhibited colony formation, and impaired migration, particularly in TOV, HeLa, and HEPG2 cells. Morphological alterations were evident. The compound induced cell death, with increased sub-G1 populations, and promoted G2/M arrest. Moreover, NAF-Q69 markedly elevated ROS levels, implicating oxidative stress as a central mechanism. In conclusion, NAF-Q69 exhibits promising antitumor activity by inhibiting proliferation and migration, inducing cell death, and enhancing oxidative stress, supporting the potential of naphthoquinones in cancer therapy.
Insights
A synthetic naphthoquinone, NAF-Q69, demonstrates significant antitumor potential by inhibiting cancer cell growth, migration, and colony formation. This compound effectively induces cancer cell death via increased reactive oxygen species (ROS) and cell cycle arrest.
Area of Science:
- Pharmacology
- Oncology
- Biochemistry
Background:
- Cancer remains a significant global health burden, necessitating novel therapeutic strategies.
- Naturally derived compounds, including naphthoquinones, show promise for cancer treatment due to their antitumor potential.
- Conventional cancer therapies face limitations, driving research into alternative agents.
Purpose of the Study:
- To evaluate the in vitro antitumor effects of β-isopropylfuran-1,2-naphthoquinone (NAF-Q69), a synthetic isolapachol derivative.
- To assess NAF-Q69's impact on cancer cell viability, proliferation, migration, morphology, cell cycle, and reactive oxygen species (ROS) production.
- To investigate the potential of NAF-Q69 as a novel therapeutic agent in cancer therapy.
Main Methods:
- In vitro evaluation of NAF-Q69 on multiple human cancer cell lines (HEPG2, HeLa, TOV, MDA-MB, J82) and a normal cell line (MRC-5).
- Assays included cytotoxicity (IC50 determination), clonogenic survival, migration, morphology, cell cycle analysis, and ROS production.
- Dose-dependent effects of NAF-Q69 were analyzed across various cancer types.
Main Results:
- NAF-Q69 exhibited significant dose-dependent cytotoxicity against all tested tumor cell lines, with IC50 values between 10.29 µM and 18.65 µM.
- The compound inhibited colony formation and impaired cell migration, particularly in ovarian, cervical, and liver cancer cells.
- NAF-Q69 induced morphological changes, increased sub-G1 populations indicating cell death, promoted G2/M cell cycle arrest, and markedly elevated ROS levels.
Conclusions:
- NAF-Q69 demonstrates potent in vitro antitumor activity across various human cancer cell lines.
- The mechanism of action involves inhibition of proliferation and migration, induction of cell death, and enhancement of oxidative stress via ROS production.
- NAF-Q69 shows promise as a potential therapeutic candidate in cancer treatment, warranting further investigation.
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