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Updated: Jun 22, 2026

Experimental Protocol for Detecting Mitochondrial Function in Hepatocytes Exposed to Organochlorine Pesticides
Published on: September 16, 2020
MAC-related mitochondrial pathway in oroxylin-A-induced apoptosis in human hepatocellular carcinoma HepG2 cells
Wei Liu1, Rong Mu, Fei-Fei Nie
1Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
Abstract:
Oroxylin A is a flavonoid isolated from the root of Scutellaria baicalensis Georgi. Our previous work demonstrated that the anti-tumor activity of oroxylin A was mainly attributed to its apoptosis inducing effect in cells. The present study explores the exact molecular mechanism of oroxylin A-induced apoptosis in tumor cells. We showed that oroxylin A-induced apoptosis in HepG2 cells was achieved through mitochondrial pathway. We also investigated which mitochondrial channels, PTP or MAC or both, were involved in the permeabilization of the mitochondrial outer membrane after treatment with oroxylin A. The results showed that oroxylin A-induced apoptosis in a PTP-independent manner; therefore, we focused our attention on MAC. As Bax is an essential constituent of MAC in certain systems, we examined the activation, subcellular location, oligomeric structure of Bax in HepG2 cells treated with oroxylin A. Moreover, our results showed that overexpression of Bcl-2 inhibited oroxylin A-induced apoptosis. In summary, we have demonstrated that opening of MAC, but not PTP, played a key role in oroxylin A-induced activation of mitochondrial apoptotic pathway in HepG2 cells.
Insights
Oroxylin A triggers tumor cell death via the mitochondrial apoptotic pathway, specifically through the mitochondrial apoptosis-inducing channel (MAC), not the permeability transition pore (PTP). This research clarifies oroxylin A's anti-tumor mechanism.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Oroxylin A, a flavonoid from Scutellaria baicalensis, exhibits anti-tumor properties.
- Previous studies linked oroxylin A's efficacy to apoptosis induction.
Purpose of the Study:
- To elucidate the precise molecular mechanism of oroxylin A-induced apoptosis in tumor cells.
- To investigate the role of mitochondrial channels, specifically the permeability transition pore (PTP) and mitochondrial apoptosis-inducing channel (MAC), in this process.
Main Methods:
- HepG2 cells were treated with oroxylin A.
- Mitochondrial pathway involvement was assessed.
- PTP and MAC involvement was investigated.
- Bax activation, localization, and oligomerization were analyzed.
- Bcl-2 overexpression effects were studied.
Main Results:
- Oroxylin A induced apoptosis in HepG2 cells through the mitochondrial pathway.
- Apoptosis occurred independently of PTP, implicating MAC.
- Oroxylin A treatment led to Bax activation and altered subcellular localization.
- Overexpression of Bcl-2 attenuated oroxylin A-induced apoptosis.
Conclusions:
- Oroxylin A-induced apoptosis in HepG2 cells is mediated by the mitochondrial pathway.
- The opening of MAC, not PTP, is crucial for activating this apoptotic cascade.
- Bax plays a key role in oroxylin A's apoptotic effects via MAC.
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