Related Experiment Video

Updated: Apr 3, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
08:35

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Published on: October 5, 2012

8.4K

B4G2 induces mitochondrial apoptosis by the ROS-mediated opening of Ca(2+)-dependent permeability transition pores

Nan Yao1, Ying-Jie Li, Dong-Mei Zhang

  • 1Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy, Jinan University, Guangzhou, China.

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
|September 19, 2015
PubMed
Abstract

Insights

A novel compound, B4G2, effectively inhibits hepatocellular carcinoma (HCC) growth. It induces programmed cell death (apoptosis) in liver cancer cells via reactive oxygen species (ROS) and calcium-dependent pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Hepatocellular carcinoma (HCC) is a prevalent liver cancer with limited treatment options, primarily sorafenib.
  • A novel 23-hydroxybetulinic acid derivative, B4G2, demonstrates significant antiproliferative effects against HCC cell lines.

Purpose of the Study:

  • To evaluate the anti-tumor activity of B4G2 in HCC.
  • To elucidate the mechanisms underlying B4G2-induced apoptosis in HCC cells.

Main Methods:

  • Utilized four HCC cell lines (HepG2, HepG2/ADM, Hep3B, Bel-7402) to assess B4G2's anti-tumor efficacy.
  • Investigated apoptosis induction pathways, including mitochondrial membrane potential, caspase activation, calcium flux, and reactive oxygen species (ROS) generation.

Main Results:

  • HepG2 cells exhibited the highest sensitivity to B4G2.
  • B4G2 induced mitochondrial apoptosis, characterized by mitochondrial depolarization, cytochrome c release, and caspase activation, independent of caspases but dependent on Ca2+-dependent permeability transition (PT) pore opening.
  • B4G2 elevated intracellular calcium and ROS levels, with ROS scavenging reducing calcium accumulation and apoptosis.

Conclusions:

  • B4G2 inhibits HCC cell growth and induces mitochondrial apoptosis.
  • The mechanism involves ROS-mediated opening of Ca2+-dependent PT pores, representing a novel therapeutic strategy for HCC.

More Related Videos

Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro13:20

Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro

Published on: July 17, 2018

10.9K
Simultaneous Measurement of Mitochondrial Calcium and Mitochondrial Membrane Potential in Live Cells by Fluorescent Microscopy08:43

Simultaneous Measurement of Mitochondrial Calcium and Mitochondrial Membrane Potential in Live Cells by Fluorescent Microscopy

Published on: January 24, 2017

19.7K

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
9.2K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
9.3K
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
17.0K
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
5.0K
Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
7.3K
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
14.6K