Rutin Isolated from Heliotropium indicum Induces Mitochondria-Mediated Apoptosis and Cytotoxicity in HepG2 and LNCaP Cancer Cells
Adeoye Y. D. *
Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria and Federal College of Animal Health and Production Technology, Moor Plantation, Ibadan, Nigeria.
James, A. B.
Center of Research in Traditional, Complementary, and Alternative Medicine, Biochemistry and Nutrition Department, Nigerian Institute of Medical Research, Yaba, Lagos, Nigeria.
Azeez, O. B.
Center of Research in Traditional, Complementary, and Alternative Medicine, Biochemistry and Nutrition Department, Nigerian Institute of Medical Research, Yaba, Lagos, Nigeria.
Oyebode O. T.
Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Olorunsogo, O. O.
Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria.
*Author to whom correspondence should be addressed.
Abstract
Aims: Locally, Heliotropium indicum L. is used as a leukemic, asthmatic, and antipyretic medication and is commonly applied in traditional medicine for treating open wounds. Species of Heliotropium have a long history of use as medicinal and culinary plants.
Study Design: This study was an in vitro cell culture–based experimental investigation with mechanistic evaluation, conducted at the Tissue Culture Laboratory, Nigerian Institute of Medical Research.
Methodology: Hepatocellular carcinoma (HepG2) and prostate carcinoma (LNCaP) cell lines were used to evaluate the cytotoxic effects of rutin purified from the methanolic extract of the whole Heliotropium indicum plant. Utilizing WST assay (lactate dehydrogenase (LDH) leakage), mitochondrial membrane potential (MMP) assay, ELISA (caspases 9/3, Bcl-2, Bax and Cytochrome c), microscopy, and fluorometry to measure apoptosis, the extracts' cytotoxicity and anti-proliferative properties were assessed in vitro via spectrophotometry
Results: Rutin significantly inhibited HepG2 and LNCaP cell proliferation in a concentration-dependent manner (0.1–1000 µg/mL). In vitro, the cytotoxic effect was more pronounced in LNCaP cells than in HepG2 cells. The significant increase in LDH leakage and decline in MMP further demonstrated the cytotoxic effects of rutin on these cells. Upregulation of caspases-9/3, Bax, and cytochrome c, alongside downregulation of Bcl-2, indicated activation of the mitochondrial apoptotic pathway in both cell lines.
Conclusion: In summary, Rutin isolated from Heliotropium indicum L. exhibits cytotoxic and apoptotic effects on HepG2 and LNCaP cells through LDH release and caspase-dependent mitochondrial apoptosis. These findings suggest the potential of Heliotropium indicum L. as a candidate for the treatment of hepatocellular and prostate cancers.
Keywords: Heliotropium indicum L., LNCaP, HepG2, cell proliferation, Rutin