β‐Caryophyllene induces apoptosis and inhibits cell proliferation by deregulation of STAT‐3/mTOR/AKT signaling in human bladder cancer cells: An in vitro study

Abstract

The current study aimed to explore the antitumor effect of β-caryophyllene (BCP) on two different cell lines of T24 and 5637 human bladder cancer (BC) cells and its potential molecular mechanisms in inhibition of STAT-3/mTOR/AKT signaling pathways and the inductive process of apoptosis mechanism. The results indicated that BCP showed significant cytotoxicity in BC T24 and 5637 cells in a doseand time-dependent manner, and IC 50 values were 40 µg/ml in the BC cells T24 and 5637. Reactive oxygen species (ROS) synthesis and apoptosis induction were significantly developed, but the mitochondrial membrane potential (Δψm) decreased on BCP treatment as detected by the fluorescence method. Moreover, cell migration was markedly reduced in BCP and Bax, Bcl-2 mRNA expression was modified. Finally, it was found that the STAT-3, mTOR, and AKT protein expressions were suppressed via inhibition of cytotoxicity in T24 and 5637 cells. Therefore, we finally concluded that BCP is an effective treatment against BC T24 and 5637 cells, and it has great chemotherapeutic potential for further bladder carcinoma treatment.

Effects of β-caryophyllene and oxygen availability on cholesterol and fatty acids in breast cancer cells

“…oncogene and is highly expressed in cancers, including breast cancer. BCP also reduces proliferation by blocking the STAT3/mTOR/AKT signaling path [62]. However, our RNAseq data from UFH-001 cells show that neither hypoxia nor BCP treatment affects either SPHK1 or STAT3.…”

“…Over the last decade, numerous studies have shown that BCP exhibits anti-proliferative properties across various carcinoma cell lines [23,[60][61][62][63][64][65][66] but hypoxia was not addressed as a specific issue despite the hypoxic nature of most solid tumors [67]. In the present study, we hypothesized that BCP might reverse the hypoxic phenotype of TNBC cells.…”

Beta-Caryophyllene Enhances the Anti-Tumor Activity of Cisplatin in Lung Cancer Cell Lines through Regulating Cell Cycle and Apoptosis Signaling Molecules

“…Beta-Caryophyllene (BCP) is a naturally occurring sesquiterpene can be extracted from several plants, including red pepper, rosemary, hops, and numerous essential oils and cannabis. Recently, it has been reported to reduce the growth and the proliferation rate of numerous cancer cells, including colorectal cancer [ 1 ], ovarian cancer [ 2 ], human bladder cancer [ 3 ] and lung cancer [ 4 , 5 , 6 ]. Beta-Caryophyllene exerting anti-proliferative activities in lung cancer cells A549 and NCI-H358 cells has been attributed to the induction of G 1 phase cell cycle arrest through downregulating cyclin D1, and other cyclin-dependent kinases, which was associated with upregulating p21CIP1 and p27KIP1 [ 5 ].…”