Geranylated 4-phenylcoumarins extracted from Mesua elegans induced caspase-independent cell death in prostate cancer cell lines through calpain-2 and cathepsin B

• Published in: Scientific reports 2020-01, Vol.10 (1), p.986-986, Article 986
• Main Authors: Sapili, Hani, Ho, Chai San, Malagobadan, Sharan, Arshad, Norhafiza Mohd, Nagoor, Noor Hasima
• Format: Article
• Language: English
• Subjects: 14/34; 631/61; 631/67; 631/80/82/23; 82; 82/1; 82/29; 82/80; 96/106; 96/2; 96/31; 96/63; Apoptosis; Apoptosis - drug effects; Calcium; Calpain; Calpain - metabolism; Caspase; Cathepsin B; Cathepsin B - metabolism; Cell death; Cell Death - drug effects; Cell Line, Tumor; Coumarins - pharmacology; Cytoplasm; DNA damage; Endoplasmic reticulum; Flow cytometry; Homeostasis; Humanities and Social Sciences; Humans; Magnoliopsida; Male; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mortality; multidisciplinary; Plant Extracts - pharmacology; Prostate - drug effects; Prostate - metabolism; Prostate - pathology; Prostate cancer; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Proteinase; Science; Science (multidisciplinary); Superoxide; Translocation; Tumor cell lines; Western blotting
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-57781-6

Geranylated 4-phenylcoumarins DMDP-1 and DMDP-2 isolated from Mesua elegans were elucidated for their role in inducing caspase-independent programmed cell death (CI-PCD) in prostate cancer cell lines, PC-3 and DU 145, respectively. Cell homeostasis disruption was demonstrated upon treatment, as shown by the increase in calcium ion through colourimetric assay and endoplasmic reticulum (ER) stress markers GRP 78 and p-eIF2α through western blot. Subsequently, cytoplasmic death protease calpain-2 also showed increased activity during DMDP-1 & -2 treatments, while lysosomic death protease cathepsin B activity was significantly increased in PC-3 treated with DMDP-1. Flow cytometry showed a reduction in mitochondrial membrane potential in both cell lines, while western blotting showed translocation of mitochondrial death protease AIF into the cytoplasm in its truncated form. Furthermore, DMDP-1 & -2 treatments caused significant increase in superoxide level and oxidative DNA damage. Concurrent inhibition of calpain-2 and cathepsin B during the treatment showed an attenuation of cell death in both cell lines. Hence, DMDP-1 & -2 induce CI-PCD in prostate cancer cell lines through calpain-2 and cathepsin B.