Euphorbiasteroid Induces Apoptosis as Well as Autophagy through Modulating SHP-1/STAT3 Pathway in Hepatocellular
Na Young Kim1, Gautam Sethi2, Jae-Young Um1
1Department of Science in Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
Abstract:
Euphorbiasteroid (EPBS) has gained attention for its activity against human lung cancer and sarcoma; however, its impact on hepatocellular carcinoma has not yet been elucidated. Here, we investigated the cytotoxic effect of EPBS on human hepatocellular carcinoma (HCC) cells. We found that EPBS induced both apoptosis and autophagy in HCC cells. Additionally, we observed that EPBS treatment suppressed the constitutive as well as the inducible activation of a signal transducer and activator of transcription 3 (STAT3) protein expression. Moreover, EPBS promoted the expression of SHP-1 protein and the production of reactive oxidative stress (ROS). Furthermore, the knockdown of SHP-1 by siRNA transfection reversed the effects of EPBS, which have inductive effects related to apoptosis and autophagy. Therefore, EPBS can potentially function as an anti-cancer agent by inducing apoptosis and autophagy when targeting the SHP-1/STAT3 pathway.
Insights
Euphorbiasteroid (EPBS) shows potential as an anti-cancer agent for hepatocellular carcinoma (HCC). It induces apoptosis and autophagy by targeting the SHP-1/STAT3 pathway, offering a new therapeutic strategy for HCC.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Hepatocellular carcinoma (HCC) remains a significant global health challenge.
- The anti-cancer properties of Euphorbiasteroid (EPBS) have been noted in lung cancer and sarcoma, but its effect on HCC is unknown.
Purpose of the Study:
- To investigate the cytotoxic effects of Euphorbiasteroid (EPBS) on human hepatocellular carcinoma (HCC) cells.
- To elucidate the molecular mechanisms underlying EPBS's action in HCC.
Main Methods:
- Treatment of HCC cells with EPBS.
- Analysis of apoptosis and autophagy induction.
- Assessment of signal transducer and activator of transcription 3 (STAT3) protein expression.
- Evaluation of SHP-1 protein expression and reactive oxidative stress (ROS) production.
- Silencing of SHP-1 using siRNA to observe the reversal of EPBS effects.
Main Results:
- EPBS induced apoptosis and autophagy in HCC cells.
- EPBS suppressed both constitutive and inducible STAT3 activation.
- EPBS treatment increased SHP-1 protein expression and ROS production.
- Knockdown of SHP-1 reversed the apoptosis- and autophagy-inducing effects of EPBS.
Conclusions:
- EPBS exhibits anti-cancer potential against HCC by inducing apoptosis and autophagy.
- The SHP-1/STAT3 signaling pathway is a key target for EPBS's anti-cancer activity in HCC.
- EPBS represents a promising therapeutic candidate for hepatocellular carcinoma treatment.
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