Piper chaba, an Indian spice plant extract, inhibits cell cycle G1/S phase transition and induces intrinsic apoptotic pathway in luminal breast cancer cells

Abstract

Piper chaba (Piperaceae) is a medicinal spice plant that possesses several pharmacological activities. In the present study, we for the first time studied the effect of P. chaba extract on breast cancer cells. P. chaba stem methanolic (PCSM) extract produced time and dose dependent cytotoxicity in luminal breast cancer cells (MCF‐7 and T47D) with a minimal toxicity in breast normal cells (MCF‐10A) at 10–100 µg/mL concentration. PCSM extract exerts 16.79 and 31.21 µg/mL IC50 for T47D and MCF‐7 cells, respectively, in 48 h treatment. PCSM significantly arrests the T47D cells at the G0/G1 phase by reducing the CCND1 and CDK4 expression at mRNA and protein levels. PCSM extract treatment significantly altered nuclear morphology, mitochondria membrane potential, and production of reactive oxygen species in T47D cells at IC50 concentration. Extract treatment significantly altered the Bax/Bcl‐2 ratio and altered caspase 8 and 3 mRNA/protein levels in T47D cells. Confocal microscopy showed an increase in late apoptosis in PCSM extract‐treated breast cancer cells at IC50. Further, an increased caspase 9 and caspase 3/7 enzymatic activity was observed in test cells compared with nontreated cells. In conclusion, P. chaba phytocompound possesses the potential to induce cell cycle arrest and induce apoptosis in luminal breast cancer cells.

Kurarinone targets JAK2‐STAT3 signaling in colon cancer‐stem‐like cells

“…In the present study, we found that KU treatment significantly increased Bax/Bcl2 ratio, cytochrome C, cleavage of Caspase 3, and PARP levels in HCT‐116 cells‐derived colonosphere. Increased Bax/Bcl2 ratio, cytochrome C release, Procaspase 3 activation, and PARP cleavage are characteristic events related to intrinsic apoptotic pathway 36,37 . Our study clearly indicates that KU induces intrinsic apoptotic pathway‐mediated cell death in HCT‐116 cells and the derived colonosphere.…”

“…[30][31][32] Our results also showed that KU Increased Bax/Bcl2 ratio, cytochrome C release, Procaspase 3 activation, and PARP cleavage are characteristic events related to intrinsic apoptotic pathway. 36,37 Our study clearly indicates that KU induces intrinsic apoptotic pathway-mediated cell death in HCT-116 cells and the derived colonosphere. Previously it has been shown that JAK2-STAT3 signaling regulates Bcl2 expression in colon cancer cells and thus regulate intrinsic apoptotic pathway in these cells.…”