Bixin Triggers Apoptosis of Human Hep3B Hepatocellular Carcinoma Cells: An Insight to Molecular and IN SILICO Approach

Abstract

Hepatocellular carcinoma (HCC) is the most common liver cancer and is known to be resistant to conventional chemotherapy. The use of herbal medicine and supplements has increased over recent decades following side effects and resistant to conventional chemotherapy. The seeds of Bixa orellana L. commonly known as annatto have recently gained scientific attention due to presence of a carotenoid bixin for its substantial anticancer properties. However, molecular mechanisms underlying bixin-induced apoptosis are still unclear. Treatment of bixin significantly decreased the number of Hep3B cells and morphological study revealed the change in cellular and nuclear morphology that trigger the events of apoptosis confirmed by annexin V/PI staining. Further DCFDA and rhodamine 123 spectrofluorimetry study showed elevation in reactive oxygen species (ROS) production and loss of mitochondrial membrane potential (MMP), respectively. ROS production caused DNA damage and apoptosis was marked by cell cycle arrest, up-regulation of Bax and FasL protein as well as cleavage of caspase-9, caspase-8 and caspase-3 protein. Docking study with pro-apoptotic molecule Bax and surface Fas ligand exhibited energetically favourable binding interaction. Collectively, these results suggest that bixin capable of modulating the extrinsic and intrinsic molecules of apoptosis indicating its potential for development of promising candidate for hepatocellular carcinoma.

Bixin Attenuates Experimental Autoimmune Encephalomyelitis by Suppressing TXNIP/NLRP3 Inflammasome Activity and Activating NRF2 Signaling

“…Bixin is a natural carotenoid with multiple bioactivities. Previous studies have shown that bixin has anti-inflammation, anti-tumor, and anti-oxidative effects (30)(31)(32)(33)(34). Xu Z et al (19) have found that bixin attenuates cardiac injury by inhibiting inflammation and oxidative stress in a high-fat-diet mouse model.…”

“…Bixin is a natural carotenoid with multiple bioactivities. Previous studies have shown that bixin has anti-inflammation, anti-tumor, and anti-oxidative effects ( 30 – 34 ). Xu Z et al.…”

Bixin Attenuates Experimental Autoimmune Encephalomyelitis by Suppressing TXNIP/NLRP3 inflammasome Activity and Activating Nrf2 Signaling

“…Bixin is a natural carotenoid with multiple bioactivities. Previous studies have shown that bixin has antiin ammation, anti-tumor, and anti-oxidative effects [28][29][30][31][32]. Xu Z et al [19] have found that bixin attenuates cardiac injury by inhibiting in ammation and oxidative stress in a high-fat-diet mouse model.…”

Intracellular ethanol‐mediated oxidation and apoptosis in HepG2/CYP2E1 cells impaired by two active peptides from seahorse (Hippocampus kuda bleeler) protein hydrolysates via the Nrf2/HO‐1 and akt pathways

“…The structures of SHP‐1 and SHP‐2 were constructed using the Chem Office 2004 software (Cambridge Soft Co.). The protein crystal structures of SOD (ID: 1CBJ; Mi et al., 2018), bcl‐2 (ID: 1YSW; Yao et al., 2019), and bax (ID: 4ZIE; Kumar et al., 2018) were derived from the RCSB Protein Data Bank. The types of interactions between the docked proteins and the ligand were analyzed with molecular docking.…”